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Harrison, Michael Roger

Positions:

Assistant Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2004

M.D. — Tulane University

Residency, Medicine

Tulane University

Grants:

Randomized Phase 2 Trial of ACP-196 and Pembrolizumab Immunotherapy Dual Checkpoint Inhibition in Platinum Resistant Metastatic Urothelial Carcinoma

Administered By
Duke Cancer Institute
AwardedBy
Acerta Pharma
Role
Principal Investigator
Start Date
May 01, 2015
End Date
April 30, 2020

A Phase III, open-label, multi-center, randomized study to investigate the efficacy and safety of MPDL3280A

Administered By
Duke Cancer Institute
AwardedBy
F. Hoffmann-La Roche Ltd
Role
Principal Investigator
Start Date
February 01, 2015
End Date
January 31, 2020

A Phase 3, Randomized, Open-Label Study of Nivolumab Combined with Ipilimumab Versus

Administered By
Duke Cancer Institute
AwardedBy
The Bristol-Myers/Sanofi Pharmaceuticals, Inc. Partnership
Role
Principal Investigator
Start Date
January 01, 2015
End Date
December 31, 2019

Metastatic Renal Cell Cancer Registry (MaRCC Registry)

Administered By
Duke Cancer Institute
AwardedBy
Pfizer, Inc.
Role
Principal Investigator
Start Date
April 01, 2014
End Date
March 31, 2019

RNA Extraction and Amplification from Biopsy Specimens in Subjects with Metastatic Renal Cell Carcinoma

Administered By
Duke Cancer Institute
AwardedBy
Argos Therapeutics, Inc.
Role
Principal Investigator
Start Date
November 01, 2013
End Date
October 31, 2018

EXTEND PC: Safety and Efficacy of Exercise Training in Men Receiving Enzalutamide in Cominbation iwth Conventional Andr

Administered By
Duke Cancer Institute
AwardedBy
Medivation, Inc.
Role
Principal Investigator
Start Date
October 01, 2014
End Date
September 30, 2018

Cardiopulmonary Exercise Testing (CPET) in Patients Treated with Schedule 2/1 and 4/2 for Metastic Renal Cell Carcinoma: A Randomized Multi-Site Trial

Administered By
Duke Cancer Institute
AwardedBy
Pfizer, Inc.
Role
Principal Investigator
Start Date
December 20, 2016
End Date
June 01, 2018

True NTH Project

Administered By
Surgery, Urology
AwardedBy
Movember Foundation
Role
Co Investigator
Start Date
March 01, 2015
End Date
February 28, 2018

Bladder Cancer in Older Adults - Treatment and Outcomes

Administered By
Duke Clinical Research Institute
AwardedBy
AstraZeneca Pharmaceuticals, LP
Role
Co Investigator
Start Date
September 08, 2016
End Date
December 31, 2017

PCRP Clinical Consortium: Duke University Clinical Research Site

Administered By
Medicine, Medical Oncology
AwardedBy
Department of Defense
Role
Investigator
Start Date
March 01, 2007
End Date
September 29, 2017

Development of Circulating Molecular Predictors of Chemotherapy and Novel Hormonal Therapy Benefit in Men with Metastatic Castration Resistant Prostate Cancer (mCRPC)

Administered By
Medicine, Medical Oncology
AwardedBy
Prostate Cancer Foundation
Role
Collaborator
Start Date
August 01, 2014
End Date
August 01, 2017

A Phase 2, Randomized, 3-Arm Study of Abiraterone Acetate alone, Abiraterone Acetate Plus Degarelix, a GnRH Antagonist,

Administered By
Duke Cancer Institute
AwardedBy
Memorial Sloan-Kettering Cancer Center
Role
Principal Investigator
Start Date
January 01, 2014
End Date
December 31, 2016
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Publications:

Phase Ib Trial of Cabazitaxel and Tasquinimod in Men With Heavily Pretreated Metastatic Castration Resistant Prostate Cancer (mCRPC): The CATCH Trial.

Tasquinimod is an immunomodulating and anti-antiangiogenic oral agent with anti-prostate cancer activity in preclinical studies and in clinical trials of men with metastatic castration resistant prostate cancer (mCRPC), including single agent activity and in combination with taxanes. We sought to identify the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of tasquinimod in combination with cabazitaxel and prednisone in men with chemorefractory mCRPC.Men with mCRPC who had failed prior docetaxel chemotherapy received cabazitaxel 25 mg/m2 every 3 weeks with oral tasquinimod at 1 of 3 escalating dose levels (0.25, 0.5, and 1.0 mg once daily) with prednisone and PEG-filgastrim support, using a 3 + 3 dose escalation design. Treatment continued until progressive disease or unacceptable toxicity.We enrolled 25 men with chemorefractory mCRPC. The RP2D was 0.5 mg tasquinimod based on excess DLTs (two of three men) observed at dose level 3 (1.0 mg) including grade 3 sensory neuropathy and grade 3 atrial fibrillation. Dose level 2 was expanded to 14 men, where 3 DLTs were observed: grade 3 fatigue, grade 4 febrile neutropenia, and grade 3 liver function abnormalities. The proportion of men with a ≥30% PSA decline was 63% and the median composite progression-free survival (PFS) was 8.5 months (95% CI 4.2-16.4 months) based on 12 PFS events. The median number of cycles of cabazitaxel was 6 (range 1-13), with six men receiving >10 cycles. Best overall RECIST responses (CR + PR) were observed in three men (12%), with stable disease in 12 (48%). No pharmacokinetic interactions were observed.We determined the RP2D of tasquinimod combined with cabazitaxel to be 0.5 mg daily following a 3 week lead-in of tasquinimod 0.25 mg with growth factor support. No unexpected toxicities occurred. Prostate 77: 385-395, 2017. © 2016 Wiley Periodicals, Inc.

Authors
Armstrong, AJ; Humeniuk, MS; Healy, P; Szmulewitz, R; Winters, C; Kephart, J; Harrison, MR; Martinez, E; Mundy, K; Halabi, S; George, D
MLA Citation
Armstrong, AJ, Humeniuk, MS, Healy, P, Szmulewitz, R, Winters, C, Kephart, J, Harrison, MR, Martinez, E, Mundy, K, Halabi, S, and George, D. "Phase Ib Trial of Cabazitaxel and Tasquinimod in Men With Heavily Pretreated Metastatic Castration Resistant Prostate Cancer (mCRPC): The CATCH Trial." March 2017.
PMID
27862097
Source
epmc
Published In
The Prostate
Volume
77
Issue
4
Publish Date
2017
Start Page
385
End Page
395
DOI
10.1002/pros.23277

Prostate-specific antigen response in black and white patients treated with abiraterone acetate for metastatic castrate-resistant prostate cancer.

Evidence suggests differences in androgen receptor AR signaling between black (B) and white (W) patients with prostate cancer, but pivotal trials of abiraterone acetate (AA) for patients with metastatic castration-resistant prostate cancer (mCRPC) enrolled few black patients, a population with a higher mortality from prostate cancer. Our primary objective was to determine differences in response to AA between B and W patients.We performed a retrospective case-control study of B vs. W patients treated with AA between May 1, 2008 and June 16, 2015 at Duke University Medical Center. Patients were identified (W control patients were matched 2:1 to B patients stratified based on previous docetaxel exposure) through pharmacy records and were eligible if treated with AA for metastatic castration-resistant prostate cancer. Patients with previous enzalutamide use were excluded. The primary objective was to compare the rate of≥90% prostate-specific antigen (PSA) decline from baseline between B vs. W patients. Secondary outcomes included comparing time on therapy, time to PSA progression, and overall survival among groups.Baseline characteristics among patients (n = 45 B, n = 90 W) were identified; these included Karnofsky performance status, PSA, Gleason score, alkaline phosphatase, albumin, hemoglobin, lactate dehydrogenase, opiate use for pain, and metastatic sites. Baseline characteristics among groups were similar except for median hemoglobin (B = 11.4g/dl, W = 12.3g/dl). The proportion of B patients achieving a≥90% PSA level decline was 37.8% vs. 28.9% for W patients (P = 0.296). Statistically significant differences were found in the proportion of patients achieving a≥50% PSA level decline (B = 68.9%, W = 48.9% [P = 0.028]) and≥30% PSA level decline (B = 77.8%, W = 54.4% [P = 0.008]). Rates of primary abiraterone-refractory disease (PSA increase as best response) trended higher in W (31.1%) than in B (15.6%) patients (P = 0.052). Median treatment duration (B = 9.4 mo, W = 8.3 mo) did not differ (Wilcoxon P = 0.444). Median overall survival (B = 27.3 mo [95% CI: 13.9, not estimable], W = 24.8 mo [95% CI: 19, 31.6] [P = 0.669]) and median time to PSA progression (B = 11.0 mo [95% CI: 4.3, 18.0], W = 9.4 mo [95% CI: 6.2, 13.0] [P = 0.917]) did not differ.Black patients may have a higher PSA response to AA than white patients. An ongoing prospective clinical study (NCT01940276) is evaluating outcomes between black and white patients treated with AA.

Authors
Ramalingam, S; Humeniuk, MS; Hu, R; Rasmussen, J; Healy, P; Wu, Y; Harrison, MR; Armstrong, AJ; George, DJ; Zhang, T
MLA Citation
Ramalingam, S, Humeniuk, MS, Hu, R, Rasmussen, J, Healy, P, Wu, Y, Harrison, MR, Armstrong, AJ, George, DJ, and Zhang, T. "Prostate-specific antigen response in black and white patients treated with abiraterone acetate for metastatic castrate-resistant prostate cancer." Urologic oncology (January 23, 2017).
PMID
28126272
Source
epmc
Published In
Urologic Oncology: Seminars and Original Investigations
Publish Date
2017
DOI
10.1016/j.urolonc.2016.12.016

Treatment-related neuroendocrine prostate cancer resulting in Cushing's syndrome.

Here we present, to the best of our knowledge, the first case of a paraneoplastic Cushing's syndrome (hypercortisolism) resulting from treatment-related neuroendocrine prostate cancer - a highly aggressive and difficult disease to treat. A 51-year-old man was started on androgen deprivation therapy after presenting with metastatic prostate cancer, characterized by diffuse osseous metastasis. Shortly thereafter, he developed progressive disease with biopsy proven neuroendocrine prostate cancer as well as symptoms of increased skin pigmentation, hypokalemia, hypertension, hyperglycemia and profound weakness, consistent with ectopic Cushing's syndrome. Molecular analysis of the patient's tumor through RNA sequencing showed high expression of several genes including CHGA, ASCL1, CALCA, HES6, PCSK1, CALCB and INSM1 confirming his neuroendocrine phenotype; elevated POMC expression was found, supporting the diagnosis of ectopic Cushing's syndrome.

Authors
Ramalingam, S; Eisenberg, A; Foo, WC; Freedman, J; Armstrong, AJ; Moss, LG; Harrison, MR
MLA Citation
Ramalingam, S, Eisenberg, A, Foo, WC, Freedman, J, Armstrong, AJ, Moss, LG, and Harrison, MR. "Treatment-related neuroendocrine prostate cancer resulting in Cushing's syndrome." International journal of urology : official journal of the Japanese Urological Association 23.12 (December 2016): 1038-1041.
PMID
27766686
Source
epmc
Published In
International Journal of Urology
Volume
23
Issue
12
Publish Date
2016
Start Page
1038
End Page
1041
DOI
10.1111/iju.13225

High rates of venous thromboembolic events in patients undergoing systemic therapy for urothelial carcinoma: A systematic review and meta-analysis.

Patients undergoing systemic therapy for urothelial carcinoma (UC) are at increased risk for venous thromboembolic (VTE) events. The objective of the current study was to determine the rate of VTE events in patients undergoing systemic therapy for UC and assess factors affecting this rate.This study was registered with the PROSPERO database (CRD42015025774). We searched Pubmed, MEDLINE, EMBASE, The Cochrane Library, CINAHL, and Web of Science libraries through August 2014. As per PRISMA guidelines, 2 reviewers independently reviewed titles and abstracts. Disagreements were arbitrated by a third reviewer. After full text review, data were abstracted and pooled using a random effects model. Authors were contacted for clarification of data. To determine VTE risk factors, subgroup analyses and meta-regression were conducted.We identified 3,635 publications in the initial search, of which 410 met inclusion criteria for full text review. Of these, we were able to obtain data on the outcome of interest for 62 publications. A total of 5,082 patients, of which 77% were male, underwent systemic therapy for UC, with 373 VTE events. The proportion of patients who had had prior surgery, chemotherapy, or radiation was 55%, 25%, and 9%, respectively. Fixed effects and random effects models were used to estimate the VTE rate, yielding event rates of 6.7% and 5.4%, respectively.VTE occurs frequently in patients undergoing systemic therapy for UC. The VTE rate was affected by the country of origin, history of radiation, as well as by the systemic treatment class. The study was limited by the incomplete reporting of all variables of interest.

Authors
Gopalakrishna, A; Longo, TA; Fantony, JJ; Doshi, U; Harrison, MR; Van Noord, M; Inman, BA
MLA Citation
Gopalakrishna, A, Longo, TA, Fantony, JJ, Doshi, U, Harrison, MR, Van Noord, M, and Inman, BA. "High rates of venous thromboembolic events in patients undergoing systemic therapy for urothelial carcinoma: A systematic review and meta-analysis." Urologic oncology 34.9 (September 2016): 407-414. (Review)
PMID
27267581
Source
epmc
Published In
Urologic Oncology: Seminars and Original Investigations
Volume
34
Issue
9
Publish Date
2016
Start Page
407
End Page
414
DOI
10.1016/j.urolonc.2016.05.009

Development of a Novel c-MET-Based CTC Detection Platform.

Amplification of the MET oncogene is associated with poor prognosis, metastatic dissemination, and drug resistance in many malignancies. We developed a method to capture and characterize circulating tumor cells (CTC) expressing c-MET using a ferromagnetic antibody. Immunofluorescence was used to characterize cells for c-MET, DAPI, and pan-CK, excluding CD45(+) leukocytes. The assay was validated using appropriate cell line controls spiked into peripheral blood collected from healthy volunteers (HV). In addition, peripheral blood was analyzed from patients with metastatic gastric, pancreatic, colorectal, bladder, renal, or prostate cancers. CTCs captured by c-MET were enumerated, and DNA FISH for MET amplification was performed. The approach was highly sensitive (80%) for MET-amplified cells, sensitive (40%-80%) for c-MET-overexpressed cells, and specific (100%) for both c-MET-negative cells and in 20 HVs. Of 52 patients with metastatic carcinomas tested, c-MET CTCs were captured in replicate samples from 3 patients [gastric, colorectal, and renal cell carcinoma (RCC)] with 6% prevalence. CTC FISH demonstrated that MET amplification in both gastric and colorectal cancer patients and trisomy 7 with gain of MET gene copies in the RCC patient. The c-MET CTC assay is a rapid, noninvasive, sensitive, and specific method for detecting MET-amplified tumor cells. CTCs with MET amplification can be detected in patients with gastric, colorectal, and renal cancers.This study developed a novel c-MET CTC assay for detecting c-MET CTCs in patients with MET amplification and warrants further investigation to determine its clinical applicability. Mol Cancer Res; 14(6); 539-47. ©2016 AACR.

Authors
Zhang, T; Boominathan, R; Foulk, B; Rao, C; Kemeny, G; Strickler, JH; Abbruzzese, JL; Harrison, MR; Hsu, DS; Healy, P; Li, J; Pi, C; Prendergast, KM; Hobbs, C; Gemberling, S; George, DJ; Hurwitz, HI; Connelly, M; Garcia-Blanco, MA; Armstrong, AJ
MLA Citation
Zhang, T, Boominathan, R, Foulk, B, Rao, C, Kemeny, G, Strickler, JH, Abbruzzese, JL, Harrison, MR, Hsu, DS, Healy, P, Li, J, Pi, C, Prendergast, KM, Hobbs, C, Gemberling, S, George, DJ, Hurwitz, HI, Connelly, M, Garcia-Blanco, MA, and Armstrong, AJ. "Development of a Novel c-MET-Based CTC Detection Platform." Molecular cancer research : MCR 14.6 (June 2016): 539-547.
Website
http://hdl.handle.net/10161/11944
PMID
26951228
Source
epmc
Published In
Molecular cancer research : MCR
Volume
14
Issue
6
Publish Date
2016
Start Page
539
End Page
547
DOI
10.1158/1541-7786.mcr-16-0011

Resistance exercise training in patients with genitourinary cancers to mitigate treatment-related skeletal muscle loss.

The use of targeted therapies in patients with genitourinary malignancies has significantly improved outcomes. For example, androgen receptor (AR) pathway inhibitors have improved outcomes for patients with prostate cancer, and antiangiogenic agents have improved outcomes for those with kidney cancer. However, these advances have been accompanied by musculoskeletal side effects that manifest as physical dysfunction. Although the effects of androgen deprivation therapy on skeletal muscle are well-known, an additional concern is that the muscle loss associated with these newer drugs-especially AR pathway inhibitors-may result in insulin resistance and metabolic syndrome, thus increasing the risk for cardiovascular events and diabetes. Antiangiogenic agents also may cause muscle loss, although this has been poorly described in the literature. As these targeted therapies begin to be used in the earlier stages of treatment, there will be a critical need to prevent treatment-related toxicities with nonpharmacologic interventions. Over the past decade, exercise training has emerged as a novel nonpharmacologic adjunctive method to address toxicities resulting from these targeted therapies. Despite numerous studies in patients with prostate cancer, there remains a large gap in our knowledge of the true efficacy of exercise therapy, as well as the best way to prescribe exercise programs. Here, we suggest that the central role of skeletal muscle in the development of side effects of AR pathway inhibitors and antiangiogenic agents may unlock a number of unique opportunities to study how exercise prescriptions can be used more effectively. Resistance training may be a particularly important modality.

Authors
Glass, OK; Ramalingam, S; Harrison, MR
MLA Citation
Glass, OK, Ramalingam, S, and Harrison, MR. "Resistance exercise training in patients with genitourinary cancers to mitigate treatment-related skeletal muscle loss." Clinical advances in hematology & oncology : H&O 14.6 (June 2016): 436-446. (Review)
PMID
27379813
Source
epmc
Published In
Clinical advances in hematology & oncology : H&O
Volume
14
Issue
6
Publish Date
2016
Start Page
436
End Page
446

Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma.

Nivolumab, an anti-PD-1 immune checkpoint inhibitor, improved overall survival versus everolimus in a phase 3 trial of previously treated patients with metastatic renal cell carcinoma (mRCC). We investigated immunomodulatory activity of nivolumab in a hypothesis-generating prospective mRCC trial.Nivolumab was administered intravenously every 3 weeks at 0.3, 2, or 10 mg/kg to previously treated patients and 10 mg/kg to treatment-naïve patients with mRCC. Baseline and on-treatment biopsies and blood were obtained. Clinical activity, tumor-associated lymphocytes, PD-L1 expression (Dako immunohistochemistry; ≥5% vs. <5% tumor membrane staining), tumor gene expression (Affymetrix U219), serum chemokines, and safety were assessed.In 91 treated patients, median overall survival [95% confidence interval (CI)] was 16.4 months [10.1 to not reached (NR)] for nivolumab 0.3 mg/kg, NR for 2 mg/kg, 25.2 months (12.0 to NR) for 10 mg/kg, and NR for treatment-naïve patients. Median percent change from baseline in tumor-associated lymphocytes was 69% (CD3+), 180% (CD4+), and 117% (CD8+). Of 56 baseline biopsies, 32% had ≥5% PD-L1 expression, and there was no consistent change from baseline to on-treatment biopsies. Transcriptional changes in tumors on treatment included upregulation of IFNγ-stimulated genes (e.g., CXCL9). Median increases in chemokine levels from baseline to C2D8 were 101% (CXCL9) and 37% (CXCL10) in peripheral blood. No new safety signals were identified.Immunomodulatory effects of PD-1 inhibition were demonstrated through multiple lines of evidence across nivolumab doses. Biomarker changes from baseline reflect nivolumab pharmacodynamics in the tumor microenvironment. These data may inform potential combinations. Clin Cancer Res; 1-11. ©2016 AACR.

Authors
Choueiri, TK; Fishman, MN; Escudier, B; McDermott, DF; Drake, CG; Kluger, H; Stadler, WM; Perez-Gracia, JL; McNeel, DG; Curti, B; Harrison, MR; Plimack, ER; Appleman, L; Fong, L; Albiges, L; Cohen, L; Young, TC; Chasalow, SD; Ross-Macdonald, P; Srivastava, S; Jure-Kunkel, M; Kurland, JF; Simon, JS; Sznol, M
MLA Citation
Choueiri, TK, Fishman, MN, Escudier, B, McDermott, DF, Drake, CG, Kluger, H, Stadler, WM, Perez-Gracia, JL, McNeel, DG, Curti, B, Harrison, MR, Plimack, ER, Appleman, L, Fong, L, Albiges, L, Cohen, L, Young, TC, Chasalow, SD, Ross-Macdonald, P, Srivastava, S, Jure-Kunkel, M, Kurland, JF, Simon, JS, and Sznol, M. "Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma." Clinical cancer research : an official journal of the American Association for Cancer Research (May 11, 2016).
PMID
27169994
Source
epmc
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Publish Date
2016

Novel Androgen Receptor Signaling Inhibitors for Nonmetastatic Castration-Resistant Prostate Cancer: The Light at the End of the Tunnel-or an Oncoming Train?

Authors
Harrison, MR; Ramalingam, S
MLA Citation
Harrison, MR, and Ramalingam, S. "Novel Androgen Receptor Signaling Inhibitors for Nonmetastatic Castration-Resistant Prostate Cancer: The Light at the End of the Tunnel-or an Oncoming Train?." Oncology (Williston Park, N.Y.) 30.4 (April 1, 2016): 345-347.
Source
scopus
Published In
Oncology
Volume
30
Issue
4
Publish Date
2016
Start Page
345
End Page
347

Novel Androgen Receptor Signaling Inhibitors for Nonmetastatic Castration-Resistant Prostate Cancer: The Light at the End of the Tunnel-or an Oncoming Train?

Authors
Harrison, MR; Ramalingam, S
MLA Citation
Harrison, MR, and Ramalingam, S. "Novel Androgen Receptor Signaling Inhibitors for Nonmetastatic Castration-Resistant Prostate Cancer: The Light at the End of the Tunnel-or an Oncoming Train?." Oncology (Williston Park, N.Y.) 30.4 (April 2016): 345-347.
PMID
27085333
Source
epmc
Published In
Oncology
Volume
30
Issue
4
Publish Date
2016
Start Page
345
End Page
347

Physician treatment selection in the prospective metastatic renal cell cancer (MaRCC) registry

Authors
Costello, BA; Harrison, MR; Bhavsar, NA; Wolf, SP; Kyriakopoulos, CE; Stadler, WM; Hammers, HJ; Vaishampayan, U; Appleman, LJ; Creel, P; Samsa, GP; Richardson, EM; Johnson, KA; Borham, A; George, DJ
MLA Citation
Costello, BA, Harrison, MR, Bhavsar, NA, Wolf, SP, Kyriakopoulos, CE, Stadler, WM, Hammers, HJ, Vaishampayan, U, Appleman, LJ, Creel, P, Samsa, GP, Richardson, EM, Johnson, KA, Borham, A, and George, DJ. "Physician treatment selection in the prospective metastatic renal cell cancer (MaRCC) registry." December 2015.
Source
wos-lite
Published In
Bju International
Volume
116
Publish Date
2015
Start Page
7
End Page
7

Front-line management patterns in the prospective metastatic renal cell cancer (MaRCC) registry

Authors
Harrison, MR; Bhavsar, NA; Wolf, SP; Costello, BA; Stadler, WM; Hammers, HJ; Vaishampayan, U; Appleman, LJ; Tsao, C-K; Creel, P; Samsa, GP; Richardson, EM; Johnson, KA; Barham, A; George, DJ
MLA Citation
Harrison, MR, Bhavsar, NA, Wolf, SP, Costello, BA, Stadler, WM, Hammers, HJ, Vaishampayan, U, Appleman, LJ, Tsao, C-K, Creel, P, Samsa, GP, Richardson, EM, Johnson, KA, Barham, A, and George, DJ. "Front-line management patterns in the prospective metastatic renal cell cancer (MaRCC) registry." December 2015.
Source
wos-lite
Published In
Bju International
Volume
116
Publish Date
2015
Start Page
12
End Page
12

The metastatic renal cell carcinoma (MaRCC) Registry: a prospective academic and community-based study of metastatic renal cell cancer patients

Authors
Bhavsar, NA; Harrison, MR; Hirsch, BR; Creel, P; Wolf, SP; Samsa, GP; Richardson, EM; Johnson, KA; Borham, A; George, DJ
MLA Citation
Bhavsar, NA, Harrison, MR, Hirsch, BR, Creel, P, Wolf, SP, Samsa, GP, Richardson, EM, Johnson, KA, Borham, A, and George, DJ. "The metastatic renal cell carcinoma (MaRCC) Registry: a prospective academic and community-based study of metastatic renal cell cancer patients." December 2015.
Source
wos-lite
Published In
Bju International
Volume
116
Publish Date
2015
Start Page
3
End Page
4

Clinical Trial Participants With Metastatic Renal Cell Carcinoma Differ From Patients Treated in Real-World Practice.

Although narrow eligibility criteria improve the internal validity of clinical trials, they may result in differences between study populations and real-world patients, threatening generalizability. Therefore, we evaluated whether patients treated for metastatic renal cell cancer (mRCC) in routine clinical practice are similar to those enrolled onto clinical trials.In this cohort study, we compared baseline characteristics of patients with mRCC in phase III clinical trials of new targeted therapies and those in a retrospective registry composed of academic (Duke) and community (ACORN Network) practices.A total of 438 registry patients received sunitinib, sorafenib, temsirolimus, or pazopanib (most commonly used agents) in first-line treatment. Registry patients receiving tyrosine kinase inhibitors (sunitinib, sorafenib, or pazopanib) were more likely to have poor-risk disease by Memorial Sloan Kettering Cancer Center criteria (poor, 7.4% v 2.9%; P < .001; favorable, 30.1% v 43.8%; P < .001) and to have impaired performance status (Eastern Cooperative Oncology Group > 1, 11.1% v 0.6%; P < .001). However, registry patients receiving temsirolimus were less likely to have poor-risk disease (poor, 10.2% v 69.4%; P < .001; favorable, 16.9% v 0%; P < .001). Thus, 39.0% of registry patients would have been excluded from the phase III clinical trial testing the drug they received.Patients with mRCC treated with tyrosine kinase inhibitors in real-world clinical practice are sicker than those enrolled onto pivotal clinical trials, and more than one third are trial ineligible. Application of clinical trial findings to dissimilar populations may result in patient harm. Clinical research with more inclusive eligibility criteria is needed to appropriately guide real-world practice.

Authors
Mitchell, AP; Harrison, MR; Walker, MS; George, DJ; Abernethy, AP; Hirsch, BR
MLA Citation
Mitchell, AP, Harrison, MR, Walker, MS, George, DJ, Abernethy, AP, and Hirsch, BR. "Clinical Trial Participants With Metastatic Renal Cell Carcinoma Differ From Patients Treated in Real-World Practice." Journal of oncology practice 11.6 (November 2015): 491-497.
PMID
26330533
Source
epmc
Published In
Journal of Oncology Practice
Volume
11
Issue
6
Publish Date
2015
Start Page
491
End Page
497
DOI
10.1200/jop.2015.004929

IMMUNOMODULATORY ACTIVITY OF NIVOLUMAB IN METASTATIC RENAL CELL CARCINOMA (MRCC): ASSOCIATION OF BIOMARKERS WITH CLINICAL OUTCOMES

Authors
Choueri, TK; Fishman, MN; Escudier, B; McDermott, DF; Kluger, H; Stadler, WM; Perez-Gracia, JL; McNeel, D; Curti, B; Harrison, MR; Plimack, ER; Appleman, L; Fong, L; Drake, CG; Young, TC; Chasalow, SD; Ross-Macdonald, P; Simon, JS; Walker, D; Sznol, M
MLA Citation
Choueri, TK, Fishman, MN, Escudier, B, McDermott, DF, Kluger, H, Stadler, WM, Perez-Gracia, JL, McNeel, D, Curti, B, Harrison, MR, Plimack, ER, Appleman, L, Fong, L, Drake, CG, Young, TC, Chasalow, SD, Ross-Macdonald, P, Simon, JS, Walker, D, and Sznol, M. "IMMUNOMODULATORY ACTIVITY OF NIVOLUMAB IN METASTATIC RENAL CELL CARCINOMA (MRCC): ASSOCIATION OF BIOMARKERS WITH CLINICAL OUTCOMES." Asia-Pacific Journal of Clinical Oncology 11 (November 2015): 119-119.
Source
wos-lite
Published In
Asia-Pacific Journal of Clinical Oncology
Volume
11
Publish Date
2015
Start Page
119
End Page
119

UPDATED SURVIVAL RESULTS FROM A RANDOMIZED, DOSE-RANGING PHASE II STUDY OF NIVOLUMAB (NIVO) IN METASTATIC RENAL CELL CARCINOMA (MRCC)

Authors
Plimack, ER; Hammers, HJ; Rini, BI; McDermott, DF; Redman, BG; Kuzel, TM; Harrison, MR; Vaishampayan, UN; Drabkin, HA; George, S; Logan, TF; Margolin, KA; Xu, L-A; Waxman, IM; Motzer, RJ
MLA Citation
Plimack, ER, Hammers, HJ, Rini, BI, McDermott, DF, Redman, BG, Kuzel, TM, Harrison, MR, Vaishampayan, UN, Drabkin, HA, George, S, Logan, TF, Margolin, KA, Xu, L-A, Waxman, IM, and Motzer, RJ. "UPDATED SURVIVAL RESULTS FROM A RANDOMIZED, DOSE-RANGING PHASE II STUDY OF NIVOLUMAB (NIVO) IN METASTATIC RENAL CELL CARCINOMA (MRCC)." Asia-Pacific Journal of Clinical Oncology 11 (November 2015): 129-129.
Source
wos-lite
Published In
Asia-Pacific Journal of Clinical Oncology
Volume
11
Publish Date
2015
Start Page
129
End Page
129

What Should We Tell Patients About Physical Activity After a Prostate Cancer Diagnosis?

A number of observational studies and clinical trials have shown that physical activity after a diagnosis of prostate cancer is associated with a decrease in disease progression and an increase in survival, and that specific exercises reduce morbidity from prostate cancer treatments. However, providers need more guidance on what types of physical activity to recommend to patients across different disease states and treatments in prostate cancer, and when and how to initiate the discussion. In addition to evaluating important studies showing benefits of physical activity in patients with prostate cancer, this review suggests some evidence-based methods for incorporating physical activity interventions into clinical practice.

Authors
Ramalingam, S; Pollak, KI; Zullig, LL; Harrison, MR
MLA Citation
Ramalingam, S, Pollak, KI, Zullig, LL, and Harrison, MR. "What Should We Tell Patients About Physical Activity After a Prostate Cancer Diagnosis?." Oncology (Williston Park, N.Y.) 29.9 (September 1, 2015). (Review)
Source
scopus
Published In
Oncology
Volume
29
Issue
9
Publish Date
2015

What Should We Tell Patients About Physical Activity After a Prostate Cancer Diagnosis?

A number of observational studies and clinical trials have shown that physical activity after a diagnosis of prostate cancer is associated with a decrease in disease progression and an increase in survival, and that specific exercises reduce morbidity from prostate cancer treatments. However, providers need more guidance on what types of physical activity to recommend to patients across different disease states and treatments in prostate cancer, and when and how to initiate the discussion. In addition to evaluating important studies showing benefits of physical activity in patients with prostate cancer, this review suggests some evidence-based methods for incorporating physical activity interventions into clinical practice.

Authors
Ramalingam, S; Pollak, KI; Zullig, LL; Harrison, MR
MLA Citation
Ramalingam, S, Pollak, KI, Zullig, LL, and Harrison, MR. "What Should We Tell Patients About Physical Activity After a Prostate Cancer Diagnosis?." Oncology (Williston Park, N.Y.) 29.9 (September 2015): 680-694. (Review)
PMID
26384805
Source
epmc
Published In
Oncology
Volume
29
Issue
9
Publish Date
2015
Start Page
680
End Page
694

Exploring the Clinical Benefit of Docetaxel or Enzalutamide After Disease Progression During Abiraterone Acetate and Prednisone Treatment in Men With Metastatic Castration-Resistant Prostate Cancer.

Abiraterone acetate (AA) has demonstrated improved outcomes in men with metastatic castration-resistant prostate cancer (mCRPC). However, data are lacking on the effect of AA on subsequent efficacy of enzalutamide or docetaxel.We included men with mCRPC who received AA and subsequent enzalutamide or docetaxel by August 12, 2013. Patients were separated into 3 groups: group A, treated with AA then enzalutamide before chemotherapy; group B, treated with AA then docetaxel; and group C, treated with AA and enzalutamide after chemotherapy. The primary objective was to describe the response and overall survival with subsequent therapy.There were 28 evaluable patients who received enzalutamide after AA (9 in group A and 19 in group C) and 13 patients who received docetaxel after AA (group B). Group A patients had more visceral disease and higher baseline prostate-specific antigen (PSA) levels, and group C men had a higher level of pain and multiple poor prognostic features. Median progression-free survival was 3.6, 5.1, and 2.8 months, respectively, and median overall survival was 8.5, not reached, and 9.6 months, respectively. A ≥ 50% PSA decline was achieved in 11%, 63%, and 5% of group A, B, and C patients, respectively. Radiographic or clinical progression as best response was noted in 55.5%, 30.8%, and 68.4% in each respective group.In this chart review of consecutive men with progressive mCRPC after AA, we found modest activity for enzalutamide and docetaxel, with clear cross-resistance for AA and enzalutamide. These data might inform the complex treatment decisions after AA treatment.

Authors
Zhang, T; Dhawan, MS; Healy, P; George, DJ; Harrison, MR; Oldan, J; Chin, B; Armstrong, AJ
MLA Citation
Zhang, T, Dhawan, MS, Healy, P, George, DJ, Harrison, MR, Oldan, J, Chin, B, and Armstrong, AJ. "Exploring the Clinical Benefit of Docetaxel or Enzalutamide After Disease Progression During Abiraterone Acetate and Prednisone Treatment in Men With Metastatic Castration-Resistant Prostate Cancer." Clinical genitourinary cancer 13.4 (August 2015): 392-399.
PMID
25708161
Source
epmc
Published In
Clinical genitourinary cancer
Volume
13
Issue
4
Publish Date
2015
Start Page
392
End Page
399
DOI
10.1016/j.clgc.2015.01.004

Deferred systemic therapy in patients with metastatic renal cell carcinoma.

With the advent of small-molecule "targeted" therapies, the prevailing treatment paradigm for metastatic renal cell carcinoma (mRCC) is that all patients who are able to tolerate systemic therapy should receive it. However, oncologists often defer the initiation of systemic therapy for patients with mRCC. The outcomes of and clinical reasoning behind the initial management of patients with mRCC without systemic therapy have not been well described.We conducted a retrospective cohort study of all patients with mRCC treated within the Duke University Health System and diagnosed from January 1, 2007, to January 1, 2011. We defined our cohort as patients who did not receive systemic therapy during the first year after mRCC diagnosis. The clinical rationale for the lack of immediate treatment was ascertained by manual chart review.A total of 60 of 268 patients (22%) with mRCC managed without initial systemic therapy were included in our study. The median age was 61.2 years, the median duration from diagnosis of localized RCC to development of mRCC was 41.9 months, and 91% of patients had Eastern Cooperative Oncology Group functional status of ≤ 1. Of the patients, 60% were managed with surgical metastasectomy alone, 12% received multiple local treatment modalities, 13% received active surveillance, 7% were managed supportively, and 8% were categorized as "other."The majority of patients in our cohort had favorable disease characteristics and experienced favorable outcomes with surgery alone. Our results suggest that this population could represent 20% of patients with mRCC in tertiary care settings. Prospective data are needed to evaluate deferred systemic therapy as a management strategy.

Authors
Mitchell, AP; Hirsch, BR; Harrison, MR; Abernethy, AP; George, DJ
MLA Citation
Mitchell, AP, Hirsch, BR, Harrison, MR, Abernethy, AP, and George, DJ. "Deferred systemic therapy in patients with metastatic renal cell carcinoma." Clinical genitourinary cancer 13.3 (June 2015): e159-e166.
PMID
25770767
Source
epmc
Published In
Clinical genitourinary cancer
Volume
13
Issue
3
Publish Date
2015
Start Page
e159
End Page
e166
DOI
10.1016/j.clgc.2014.12.017

Reversal of PSA progression on abiraterone acetate through the administration with food in men with metastatic castration-resistant prostate cancer.

Owing to efficacy and tolerability, abiraterone acetate (AA) is a leading treatment for men with metastatic castration-resistant prostate cancer. Increased serum concentrations of AA, such as by taking AA with food, may lead to the inhibition of additional enzymes in the androgen synthesis pathway implicated in castration-resistant prostate cancer progression.Medical records of men with metastatic castration-resistant prostate cancer (mCRPC) who received AA between 1 April 2011 and 31 December 2013 were retrospectively reviewed. The primary outcome was the percent of men with a rising PSA on AA who experienced any PSA decline within 3 months after changing the administration of AA from without food to with food. Secondary outcomes were median time on AA therapy in men who received AA therapy without food versus those that switched administration from without food to with food at PSA progression, and the percent of men who experienced any decline in serum testosterone concentration, and the rate of adverse events observed while taking AA with food.Nineteen men who switched AA administration from without food to with food and 41 patients who administered AA without food only were included in the study. Of those patients who took AA with food at PSA progression, a PSA decline was observed in 3 of the 19 (16%) men, including 3 of the 14 men who had an initial response to AA (21%). Testosterone declined in five out of seven patients from pre-food levels. The median time on AA therapy was increased by nearly 100 days in patients who switched AA administration from without food to with food. No increases in toxicity were observed.Some men with mCRPC may benefit from taking AA with food. Further prospective comparative studies are needed to determine if changing AA administration is beneficial.

Authors
Stover, JT; Moore, RA; Davis, K; Harrison, MR; Armstrong, AJ
MLA Citation
Stover, JT, Moore, RA, Davis, K, Harrison, MR, and Armstrong, AJ. "Reversal of PSA progression on abiraterone acetate through the administration with food in men with metastatic castration-resistant prostate cancer." Prostate cancer and prostatic diseases 18.2 (June 2015): 161-166.
PMID
25777155
Source
epmc
Published In
Prostate Cancer and Prostatic Diseases
Volume
18
Issue
2
Publish Date
2015
Start Page
161
End Page
166
DOI
10.1038/pcan.2015.7

Optimizing the efficiency and quality of sipuleucel-T delivery in an academic institution.

Sipuleucel-T, an autologous cellular immunotherapy, is approved for the treatment of certain patients with metastatic castration-resistant prostate cancer (mCRPC). Sipuleucel-T is the first personalized treatment for prostate cancer to be manufactured using the immune system of each individual patient. Patient preparation and compliance are critical because patients undergo serial leukapheresis and reinfusion procedures within a relatively short time period, which may result in transient reactions.The study aims to identify patients best suited for sipuleucel-T treatment, provide an overview of treatment, and encourage infusion sites to consider a primary contact model for the efficient coordination of care.Treatment experiences were evaluated from 124 patients with mCRPC who received sipuleucel-T from January 2010 to August 2013 according to current best practices. Feedback was collected from reflective interdisciplinary discussion within the sipuleucel-T delivery team (nurses, advanced practice providers, urologists, and medical oncologists).Early patient identification and education on treatment rationale, delivery, and expectations help ensure a successful sipuleucel-T treatment experience. A multidisciplinary coordinated-care process can facilitate proficient sipuleucel-T delivery, and the selection of a primary contact for care coordination offers benefits, such as clear and efficient education.

Authors
Davis, K; Wood, S; Dill, E; Fesko, Y; Bitting, RL; Harrison, MR; Armstrong, AJ; Moul, JW; George, DJ
MLA Citation
Davis, K, Wood, S, Dill, E, Fesko, Y, Bitting, RL, Harrison, MR, Armstrong, AJ, Moul, JW, and George, DJ. "Optimizing the efficiency and quality of sipuleucel-T delivery in an academic institution." Clinical journal of oncology nursing 19.3 (June 2015): 297-303.
PMID
26000580
Source
epmc
Published In
Clinical Journal of Oncology Nursing
Volume
19
Issue
3
Publish Date
2015
Start Page
297
End Page
303
DOI
10.1188/15.cjon.297-303

Evaluation of a novel c-MET based circulating tumor cell (CTC) biomarker in patients with gastrointestinal (GI) and genitourinary (GU) malignancies.

Authors
Zhang, T; Boominathan, R; Foulk, B; Connelly, MC; Rao, C; Kemeny, G; Strickler, JH; Abbruzzese, JL; Harrison, MR; George, DJ; Hurwitz, H; Garcia-Blanco, MA; Armstrong, AJ
MLA Citation
Zhang, T, Boominathan, R, Foulk, B, Connelly, MC, Rao, C, Kemeny, G, Strickler, JH, Abbruzzese, JL, Harrison, MR, George, DJ, Hurwitz, H, Garcia-Blanco, MA, and Armstrong, AJ. "Evaluation of a novel c-MET based circulating tumor cell (CTC) biomarker in patients with gastrointestinal (GI) and genitourinary (GU) malignancies." May 20, 2015.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
33
Issue
15
Publish Date
2015

Immunomodulatory activity of nivolumab in metastatic renal cell carcinoma (mRCC): Association of biomarkers with clinical outcomes

Authors
Choueiri, TK; Fishman, MN; Escudier, B; McDermott, DF; Kluger, HM; Stadler, WM; Perez-Gracia, JL; McNeel, DG; Curti, BD; Harrison, MR; Plimack, ER; Appleman, LJ; Fong, L; Drake, CG; Young, TC; Chasalow, SD; Ross-Macdonald, P; Simon, JS; Walker, D; Sznol, M
MLA Citation
Choueiri, TK, Fishman, MN, Escudier, B, McDermott, DF, Kluger, HM, Stadler, WM, Perez-Gracia, JL, McNeel, DG, Curti, BD, Harrison, MR, Plimack, ER, Appleman, LJ, Fong, L, Drake, CG, Young, TC, Chasalow, SD, Ross-Macdonald, P, Simon, JS, Walker, D, and Sznol, M. "Immunomodulatory activity of nivolumab in metastatic renal cell carcinoma (mRCC): Association of biomarkers with clinical outcomes." May 20, 2015.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
33
Issue
15
Publish Date
2015

Updated survival results from a randomized, dose-ranging phase II study of nivolumab (NIVO) in metastatic renal cell carcinoma (mRCC).

Authors
Plimack, ER; Hammers, HJ; Rini, BI; McDermott, DF; Redman, B; Kuzel, T; Harrison, MR; Vaishampayan, UN; Drabkin, HA; George, S; Logan, TF; Margolin, KA; Xu, L-A; Waxman, I; Motzer, R
MLA Citation
Plimack, ER, Hammers, HJ, Rini, BI, McDermott, DF, Redman, B, Kuzel, T, Harrison, MR, Vaishampayan, UN, Drabkin, HA, George, S, Logan, TF, Margolin, KA, Xu, L-A, Waxman, I, and Motzer, R. "Updated survival results from a randomized, dose-ranging phase II study of nivolumab (NIVO) in metastatic renal cell carcinoma (mRCC)." May 20, 2015.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
33
Issue
15
Publish Date
2015

Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial.

Nivolumab is a fully human immunoglobulin G4 programmed death-1 immune checkpoint inhibitor antibody that restores T-cell immune activity. This phase II trial assessed the antitumor activity, dose-response relationship, and safety of nivolumab in patients with metastatic renal cell carcinoma (mRCC).Patients with clear-cell mRCC previously treated with agents targeting the vascular endothelial growth factor pathway were randomly assigned (blinded ratio of 1:1:1) to nivolumab 0.3, 2, or 10 mg/kg intravenously once every 3 weeks. The primary objective was to evaluate the dose-response relationship as measured by progression-free survival (PFS); secondary end points included objective response rate (ORR), overall survival (OS), and safety.A total of 168 patients were randomly assigned to the nivolumab 0.3- (n = 60), 2- (n = 54), and 10-mg/kg (n = 54) cohorts. One hundred eighteen patients (70%) had received more than one prior systemic regimen. Median PFS was 2.7, 4.0, and 4.2 months, respectively (P = .9). Respective ORRs were 20%, 22%, and 20%. Median OS was 18.2 months (80% CI, 16.2 to 24.0 months), 25.5 months (80% CI, 19.8 to 28.8 months), and 24.7 months (80% CI, 15.3 to 26.0 months), respectively. The most common treatment-related adverse event (AE) was fatigue (24%, 22%, and 35%, respectively). Nineteen patients (11%) experienced grade 3 to 4 treatment-related AEs.Nivolumab demonstrated antitumor activity with a manageable safety profile across the three doses studied in mRCC. No dose-response relationship was detected as measured by PFS. These efficacy and safety results in mRCC support study in the phase III setting.

Authors
Motzer, RJ; Rini, BI; McDermott, DF; Redman, BG; Kuzel, TM; Harrison, MR; Vaishampayan, UN; Drabkin, HA; George, S; Logan, TF; Margolin, KA; Plimack, ER; Lambert, AM; Waxman, IM; Hammers, HJ
MLA Citation
Motzer, RJ, Rini, BI, McDermott, DF, Redman, BG, Kuzel, TM, Harrison, MR, Vaishampayan, UN, Drabkin, HA, George, S, Logan, TF, Margolin, KA, Plimack, ER, Lambert, AM, Waxman, IM, and Hammers, HJ. "Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 33.13 (May 2015): 1430-1437.
PMID
25452452
Source
epmc
Published In
Journal of Clinical Oncology
Volume
33
Issue
13
Publish Date
2015
Start Page
1430
End Page
1437
DOI
10.1200/jco.2014.59.0703

Burden of disease matters when it comes to systemic therapy for prostate cancer

Authors
Harrison, MR; Armstrong, AJ
MLA Citation
Harrison, MR, and Armstrong, AJ. "Burden of disease matters when it comes to systemic therapy for prostate cancer." European Urology 67.3 (March 1, 2015): 448-450.
Source
scopus
Published In
European Urology
Volume
67
Issue
3
Publish Date
2015
Start Page
448
End Page
450
DOI
10.1016/j.eururo.2014.02.032

Burden of disease matters when it comes to systemic therapy for prostate cancer.

Authors
Harrison, MR; Armstrong, AJ
MLA Citation
Harrison, MR, and Armstrong, AJ. "Burden of disease matters when it comes to systemic therapy for prostate cancer." European urology 67.3 (March 2015): 448-450.
PMID
24612662
Source
epmc
Published In
European Urology
Volume
67
Issue
3
Publish Date
2015
Start Page
448
End Page
450
DOI
10.1016/j.eururo.2014.02.032

Deferred systemic therapy in patients with metastatic renal cell carcinoma

© 2015 Elsevier Inc.Abstract Background With the advent of small-molecule "targeted" therapies, the prevailing treatment paradigm for metastatic renal cell carcinoma (mRCC) is that all patients who are able to tolerate systemic therapy should receive it. However, oncologists often defer the initiation of systemic therapy for patients with mRCC. The outcomes of and clinical reasoning behind the initial management of patients with mRCC without systemic therapy have not been well described. Methods We conducted a retrospective cohort study of all patients with mRCC treated within the Duke University Health System and diagnosed from January 1, 2007, to January 1, 2011. We defined our cohort as patients who did not receive systemic therapy during the first year after mRCC diagnosis. The clinical rationale for the lack of immediate treatment was ascertained by manual chart review. Results A total of 60 of 268 patients (22%) with mRCC managed without initial systemic therapy were included in our study. The median age was 61.2 years, the median duration from diagnosis of localized RCC to development of mRCC was 41.9 months, and 91% of patients had Eastern Cooperative Oncology Group functional status of ≤ 1. Of the patients, 60% were managed with surgical metastasectomy alone, 12% received multiple local treatment modalities, 13% received active surveillance, 7% were managed supportively, and 8% were categorized as "other." Conclusions The majority of patients in our cohort had favorable disease characteristics and experienced favorable outcomes with surgery alone. Our results suggest that this population could represent 20% of patients with mRCC in tertiary care settings. Prospective data are needed to evaluate deferred systemic therapy as a management strategy.

Authors
Mitchell, AP; Hirsch, BR; Harrison, MR; Abernethy, AP; George, DJ
MLA Citation
Mitchell, AP, Hirsch, BR, Harrison, MR, Abernethy, AP, and George, DJ. "Deferred systemic therapy in patients with metastatic renal cell carcinoma." Clinical Genitourinary Cancer 13.3 (January 1, 2015): e159-e166.
Source
scopus
Published In
Clinical genitourinary cancer
Volume
13
Issue
3
Publish Date
2015
Start Page
e159
End Page
e166
DOI
10.1016/j.clgc.2014.12.017

Use of "Real-World" data to describe adverse events during the treatment of metastatic renal cell carcinoma in routine clinical practice

Insights into the experience of metastatic renal cell carcinoma (mRCC) patients are needed to optimize patient care. A retrospective, multicenter registry of mRCC patients treated at academic (Duke) and community (ACORN) practices was developed to fill this need. Treatment data were collected on 466 patients who received first-line therapy from 2007 to 2011. Clinically significant adverse events (AEs) were abstracted from medical records and compared to clinical trials. Two hundred and seventy patients received first-line therapy with sunitinib, 60 temsirolimus, 53 sorafenib, 25 pazopanib, and 58 "other." A total of 85.8 % of all patients experienced at least one AE: fatigue (56.7 %), vomiting (40.1 %), diarrhea (33.7 %), asthenia (32.8 %), and mucosal inflammation (20.8 %). When comparisons were made between patients >65 versus <65 years old, rates of AEs were higher in the younger group. Dosing approaches and timing of AEs during therapy were varied. These data shine light on the patient experience in routine practice versus structured clinical trials. Real-world AE frequency and severity differ from pivotal trials demonstrating the need to monitor patients closely and manage their AEs to optimize outcomes. As the number of treatment options with similar effectiveness grows, it is imperative to understand the real-world patient experience.

Authors
Hirsch, BR; Harrison, MR; George, DJ; Walker, MS; Chen, C; Korytowsky, B; Stepanski, E; Abernethy, AP
MLA Citation
Hirsch, BR, Harrison, MR, George, DJ, Walker, MS, Chen, C, Korytowsky, B, Stepanski, E, and Abernethy, AP. "Use of "Real-World" data to describe adverse events during the treatment of metastatic renal cell carcinoma in routine clinical practice." Medical oncology (Northwood, London, England) 31.9 (September 1, 2014): 156-.
Source
scopus
Published In
Medical Oncology
Volume
31
Issue
9
Publish Date
2014
Start Page
156
DOI
10.1007/s12032-014-0156-8

Use of "Real-World" data to describe adverse events during the treatment of metastatic renal cell carcinoma in routine clinical practice.

Insights into the experience of metastatic renal cell carcinoma (mRCC) patients are needed to optimize patient care. A retrospective, multicenter registry of mRCC patients treated at academic (Duke) and community (ACORN) practices was developed to fill this need. Treatment data were collected on 466 patients who received first-line therapy from 2007 to 2011. Clinically significant adverse events (AEs) were abstracted from medical records and compared to clinical trials. Two hundred and seventy patients received first-line therapy with sunitinib, 60 temsirolimus, 53 sorafenib, 25 pazopanib, and 58 "other." A total of 85.8 % of all patients experienced at least one AE: fatigue (56.7 %), vomiting (40.1 %), diarrhea (33.7 %), asthenia (32.8 %), and mucosal inflammation (20.8 %). When comparisons were made between patients >65 versus <65 years old, rates of AEs were higher in the younger group. Dosing approaches and timing of AEs during therapy were varied. These data shine light on the patient experience in routine practice versus structured clinical trials. Real-world AE frequency and severity differ from pivotal trials demonstrating the need to monitor patients closely and manage their AEs to optimize outcomes. As the number of treatment options with similar effectiveness grows, it is imperative to understand the real-world patient experience.

Authors
Hirsch, BR; Harrison, MR; George, DJ; Walker, MS; Chen, C; Korytowsky, B; Stepanski, E; Abernethy, AP
MLA Citation
Hirsch, BR, Harrison, MR, George, DJ, Walker, MS, Chen, C, Korytowsky, B, Stepanski, E, and Abernethy, AP. "Use of "Real-World" data to describe adverse events during the treatment of metastatic renal cell carcinoma in routine clinical practice." Medical oncology (Northwood, London, England) 31.9 (September 2014): 156-.
PMID
25115744
Source
epmc
Published In
Medical Oncology
Volume
31
Issue
9
Publish Date
2014
Start Page
156
DOI
10.1007/s12032-014-0156-8

1072PEXPERIENCE OF PATIENTS TREATED WITH SIPULEUCEL-T IN AN ACADEMIC SETTING.

Authors
Bhavsar, NA; Harrison, MR; Howie, LJ; Armstrong, AJ; Davis, K; Chen, Q; Pupa, MR; Abernethy, A; George, DJ; Hirsch, BR
MLA Citation
Bhavsar, NA, Harrison, MR, Howie, LJ, Armstrong, AJ, Davis, K, Chen, Q, Pupa, MR, Abernethy, A, George, DJ, and Hirsch, BR. "1072PEXPERIENCE OF PATIENTS TREATED WITH SIPULEUCEL-T IN AN ACADEMIC SETTING." September 2014.
PMID
28171524
Source
epmc
Published In
Annals of Oncology
Volume
25
Issue
suppl_4
Publish Date
2014
Start Page
iv369
End Page
iv370

810ORANDOMIZED, DOSE-RANGING PHASE II TRIAL OF NIVOLUMAB FOR METASTATIC RENAL CELL CARCINOMA (MRCC).

Authors
Motzer, RJ; Rini, BI; McDermott, DF; Redman, B; Kuzel, T; Harrison, MR; Vaishampayan, UN; Drabkin, H; George, S; Logan, T; Margolin, K; Plimack, ER; Waxman, I; Lambert, A; Hammers, H
MLA Citation
Motzer, RJ, Rini, BI, McDermott, DF, Redman, B, Kuzel, T, Harrison, MR, Vaishampayan, UN, Drabkin, H, George, S, Logan, T, Margolin, K, Plimack, ER, Waxman, I, Lambert, A, and Hammers, H. "810ORANDOMIZED, DOSE-RANGING PHASE II TRIAL OF NIVOLUMAB FOR METASTATIC RENAL CELL CARCINOMA (MRCC)." September 2014.
PMID
28172310
Source
epmc
Published In
Annals of Oncology
Volume
25
Issue
suppl_4
Publish Date
2014
Start Page
iv281

Clinical trial subjects compared to "real world" patients: Generalizability of renal cell carcinoma trials

Authors
Mitchell, AP; Harrison, MR; George, DJ; Abernethy, AP; Walker, MS; Hirsch, BR
MLA Citation
Mitchell, AP, Harrison, MR, George, DJ, Abernethy, AP, Walker, MS, and Hirsch, BR. "Clinical trial subjects compared to "real world" patients: Generalizability of renal cell carcinoma trials." May 20, 2014.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
32
Issue
15
Publish Date
2014

Nivolumab for metastatic renal cell carcinoma (mRCC): Results of a randomized, dose-ranging phase II trial.

Authors
Motzer, RJ; Rini, BI; McDermott, DF; Redman, BG; Kuzel, T; Harrison, MR; Vaishampayan, UN; Drabkin, HA; George, S; Logan, TF; Margolin, KA; Plimack, ER; Waxman, I; Lambert, A; Hammers, HJ
MLA Citation
Motzer, RJ, Rini, BI, McDermott, DF, Redman, BG, Kuzel, T, Harrison, MR, Vaishampayan, UN, Drabkin, HA, George, S, Logan, TF, Margolin, KA, Plimack, ER, Waxman, I, Lambert, A, and Hammers, HJ. "Nivolumab for metastatic renal cell carcinoma (mRCC): Results of a randomized, dose-ranging phase II trial." May 20, 2014.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
32
Issue
15
Publish Date
2014

Immunomodulatory activity of nivolumab in previously treated and untreated metastatic renal cell carcinoma (mRCC): Biomarker-based results from a randomized clinical trial.

Authors
Choueiri, TK; Fishman, MN; Escudier, BJ; Kim, JJ; Kluger, HM; Stadler, WM; Perez-Gracia, JL; McNeel, DG; Curti, BD; Harrison, MR; Plimack, ER; Appleman, LJ; Fong, L; Drake, CG; Cohen, LJ; Srivastava, S; Jure-Kunkel, M; Hong, Q; Kurland, JF; Sznol, M
MLA Citation
Choueiri, TK, Fishman, MN, Escudier, BJ, Kim, JJ, Kluger, HM, Stadler, WM, Perez-Gracia, JL, McNeel, DG, Curti, BD, Harrison, MR, Plimack, ER, Appleman, LJ, Fong, L, Drake, CG, Cohen, LJ, Srivastava, S, Jure-Kunkel, M, Hong, Q, Kurland, JF, and Sznol, M. "Immunomodulatory activity of nivolumab in previously treated and untreated metastatic renal cell carcinoma (mRCC): Biomarker-based results from a randomized clinical trial." May 20, 2014.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
32
Issue
15
Publish Date
2014

Real-world outcomes in metastatic renal cell carcinoma: insights from a Joint Community-Academic Registry.

INTRODUCTION: As new therapeutics for metastatic renal cell carcinoma (mRCC) are quickly introduced to market, comparative randomized trial evidence guiding treatment decisions is lacking, especially in the second treatment exposure and beyond. As a demonstration case, we studied mRCC in real-world clinical settings by creating a joint community-academic retrospective mRCC registry to assess outcomes. MATERIALS AND METHODS: For this overall survival (OS) analysis, the analytic cohort included all patients in the registry diagnosed between January 1, 2007, to May 31, 2011 (N = 384). Patients were grouped by up to three treatment exposures according to each drug's mechanism of action: vascular endothelial growth factor tyrosine kinase inhibitor (VEGFR TKI), mammalian target of rapamycin inhibitor (mTOR), or no systemic treatment (NSTx, which could include radiation or surgery). OS by exposure sequence was evaluated using Kaplan-Meier, pairwise comparison, and Cox regression analyses. RESULTS: Median OS was 17.2 months. OS (months) for one exposure was: mTOR 5.4, TKI 18.2, NSTx 18.4; for two exposures: mTOR/TKI 9.3, TKI/mTOR 13.9, TKI/TKI 35.2; and for three exposures: TKI/mTOR/TKI 20.9, TKI/TKI/mTOR 33.1. By pairwise comparison, OS for TKI, mTOR/TKI, TKI/mTOR, TKI/TKI, TKI/mTOR/TKI and TKI/TKI/mTOR sequences was greater than mTOR (all P < .04); demographics confirmed that individuals treated with early mTOR inhibition more commonly had adverse prognostic features. In Cox regression analysis, compared with the referent (TKI), TKI/TKI (hazard ratio = 0.53; P = .03) had a lower risk of death, and mTOR (hazard ratio = 2.16; P = .002) had a higher risk of death. CONCLUSIONS: mRCC survival outcomes are different by pattern, with general findings consistent with trial-based expectations in similar patient populations. Real-world data can provide context around patterns of care and impact when experimental trial data are lacking.

Authors
Harrison, MR; Hirsch, BR; George, DJ; Walker, MS; Chen, C; Korytowsky, B; Stepanski, E; Abernethy, AP
MLA Citation
Harrison, MR, Hirsch, BR, George, DJ, Walker, MS, Chen, C, Korytowsky, B, Stepanski, E, and Abernethy, AP. "Real-world outcomes in metastatic renal cell carcinoma: insights from a Joint Community-Academic Registry." J Oncol Pract 10.2 (March 2014): e63-e72.
PMID
24281152
Source
pubmed
Published In
Journal of Oncology Practice
Volume
10
Issue
2
Publish Date
2014
Start Page
e63
End Page
e72
DOI
10.1200/JOP.2013.001180

Treatment selection in metastatic renal cell carcinoma: more confusion or a path forward?

Meaningful progress has been realized in the treatment of metastatic renal cell carcinoma with the recent approval of a number of new agents; more new agents are on the horizon. Despite the recent completion of many clinical trials that have changed or will change practice, many questions remain. In this manuscript, we highlight the most noteworthy developments in the first- and second-line treatment of metastatic renal cell carcinoma, as these are the areas of greatest change. We also emphasize ongoing trials and those areas that are most in need of study in order to move the field forward. Although more data are needed, exciting progress is being made.

Authors
Hirsch, BR; George, DJ; Harrison, MR
MLA Citation
Hirsch, BR, George, DJ, and Harrison, MR. "Treatment selection in metastatic renal cell carcinoma: more confusion or a path forward?." Clinical advances in hematology & oncology : H&O 12.3 (March 2014): 163-171. (Review)
PMID
24927264
Source
epmc
Published In
Clinical advances in hematology & oncology : H&O
Volume
12
Issue
3
Publish Date
2014
Start Page
163
End Page
171

Exercise as treatment for androgen deprivation therapy-associated physical dysfunction: Ready for prime time?

Authors
Harrison, MR; Jones, LW
MLA Citation
Harrison, MR, and Jones, LW. "Exercise as treatment for androgen deprivation therapy-associated physical dysfunction: Ready for prime time?." European Urology 65.5 (January 1, 2014): 873-874.
Source
scopus
Published In
European Urology
Volume
65
Issue
5
Publish Date
2014
Start Page
873
End Page
874
DOI
10.1016/j.eururo.2013.11.033

"real world" Treatment of metastatic renal cell carcinoma in a joint community-academic cohort: Progression-free survival over three lines of therapy

Background New targeted therapeutics approved for metastatic renal cell carcinoma (mRCC) offer multiple options in each line of therapy; however, there are few prospective data beyond the first-line settings, and overall comparative effectiveness data are limited. In the targeted therapy era, progression-free survival (PFS) has been the most common regulatory end point for demonstrating the benefit of new therapies. Patients and Methods Drawing on a joint community-academic retrospective mRCC registry, we analyzed all patients who had undergone at least 1 line of systemic therapy (N = 325) for PFS. Patients were grouped according to treatment choice (sorafenib, sunitinib, temsirolimus, everolimus, and "other") for up to 3 lines of therapy. PFS by treatment choice and line of therapy was evaluated using Kaplan-Meier and Cox regression analyses. Results PFS was longest in patients treated with sunitinib in the first and second lines of therapy. First-line PFS for sorafenib, sunitinib, temsirolimus, everolimus, and "other" was 6.9, 8.9, 4.2, not analyzed (too few patients), and 10.8 months, respectively. Second-line PFS was 4.6, 7.0, 3.2, 3.8, and 4.1 months, respectively. Third-line PFS was 4.5, 4.6, 9.9, 4.2, and 2.9, months, respectively. The risk of progression in patients treated with temsirolimus was about twice that of patients treated with sunitinib in the first and second lines of therapy. Conclusion Patients treated with sunitinib had the longest PFS in the first and second lines of therapy. PFS from practice-based data appear consistent with trial-based expectations; however, practice variation was still evident. © 2013 Elsevier Inc. All rights reserved.

Authors
Harrison, MR; George, DJ; Walker, MS; Chen, C; Korytowsky, B; Kirkendall, DT; Stepanski, EJ; Abernethy, AP
MLA Citation
Harrison, MR, George, DJ, Walker, MS, Chen, C, Korytowsky, B, Kirkendall, DT, Stepanski, EJ, and Abernethy, AP. ""real world" Treatment of metastatic renal cell carcinoma in a joint community-academic cohort: Progression-free survival over three lines of therapy." Clinical Genitourinary Cancer 11.4 (December 1, 2013): 441-450.
Source
scopus
Published In
Clinical genitourinary cancer
Volume
11
Issue
4
Publish Date
2013
Start Page
441
End Page
450
DOI
10.1016/j.clgc.2013.05.002

"Real world" treatment of metastatic renal cell carcinoma in a joint community-academic cohort: progression-free survival over three lines of therapy.

BACKGROUND: New targeted therapeutics approved for metastatic renal cell carcinoma (mRCC) offer multiple options in each line of therapy; however, there are few prospective data beyond the first-line settings, and overall comparative effectiveness data are limited. In the targeted therapy era, progression-free survival (PFS) has been the most common regulatory end point for demonstrating the benefit of new therapies. PATIENTS AND METHODS: Drawing on a joint community-academic retrospective mRCC registry, we analyzed all patients who had undergone at least 1 line of systemic therapy (N = 325) for PFS. Patients were grouped according to treatment choice (sorafenib, sunitinib, temsirolimus, everolimus, and "other") for up to 3 lines of therapy. PFS by treatment choice and line of therapy was evaluated using Kaplan-Meier and Cox regression analyses. RESULTS: PFS was longest in patients treated with sunitinib in the first and second lines of therapy. First-line PFS for sorafenib, sunitinib, temsirolimus, everolimus, and "other" was 6.9, 8.9, 4.2, not analyzed (too few patients), and 10.8 months, respectively. Second-line PFS was 4.6, 7.0, 3.2, 3.8, and 4.1 months, respectively. Third-line PFS was 4.5, 4.6, 9.9, 4.2, and 2.9, months, respectively. The risk of progression in patients treated with temsirolimus was about twice that of patients treated with sunitinib in the first and second lines of therapy. CONCLUSION: Patients treated with sunitinib had the longest PFS in the first and second lines of therapy. PFS from practice-based data appear consistent with trial-based expectations; however, practice variation was still evident.

Authors
Harrison, MR; George, DJ; Walker, MS; Chen, C; Korytowsky, B; Kirkendall, DT; Stepanski, EJ; Abernethy, AP
MLA Citation
Harrison, MR, George, DJ, Walker, MS, Chen, C, Korytowsky, B, Kirkendall, DT, Stepanski, EJ, and Abernethy, AP. ""Real world" treatment of metastatic renal cell carcinoma in a joint community-academic cohort: progression-free survival over three lines of therapy." Clin Genitourin Cancer 11.4 (December 2013): 441-450.
PMID
23856102
Source
pubmed
Published In
Clinical genitourinary cancer
Volume
11
Issue
4
Publish Date
2013
Start Page
441
End Page
450
DOI
10.1016/j.clgc.2013.05.002

Adverse events among patients treated for metastatic renal cell carcinoma (mRCC): Data from a real world, multicenter registry

Authors
Hirsch, B; Harrison, MR; Walker, MS; Roe, L; Chen, C; Korytowsky, B; Stepanski, EJ; George, DJ; Abernethy, AP
MLA Citation
Hirsch, B, Harrison, MR, Walker, MS, Roe, L, Chen, C, Korytowsky, B, Stepanski, EJ, George, DJ, and Abernethy, AP. "Adverse events among patients treated for metastatic renal cell carcinoma (mRCC): Data from a real world, multicenter registry." September 2013.
Source
wos-lite
Published In
European Journal of Cancer
Volume
49
Publish Date
2013
Start Page
S661
End Page
S661

Highlights in advanced prostate cancer from the 2013 American Urological Association Annual Meeting and the 2013 American Society of Clinical Oncology Annual Meeting: commentary.

Authors
George, DJ; Armstrong, AJ; Harrison, MR
MLA Citation
George, DJ, Armstrong, AJ, and Harrison, MR. "Highlights in advanced prostate cancer from the 2013 American Urological Association Annual Meeting and the 2013 American Society of Clinical Oncology Annual Meeting: commentary." Clinical advances in hematology & oncology : H&O 11 Suppl 14.9 (September 2013): 16-22.
PMID
25856023
Source
epmc
Published In
Clinical advances in hematology & oncology : H&O
Volume
11 Suppl 14
Issue
9
Publish Date
2013
Start Page
16
End Page
22

Novel immunotherapeutic strategies in development for renal cell carcinoma.

CONTEXT: The purpose of this report is to review immunotherapies under investigation for patients with renal cell carcinoma (RCC), the most common form of kidney cancer, for which the incidence and mortality rate continue to increase. OBJECTIVE: To summarize and evaluate current data on immunotherapies for RCC and discuss issues to be resolved before integration into the RCC treatment paradigm. EVIDENCE ACQUISITION: A search of Medline, clinicaltrials.gov, and congress abstracts/treatment guidelines was performed in May 2012 using the following terms (and variations): metastatic renal cell carcinoma, practice guidelines, response/resistance to current treatments, immunotherapy, novel immunotherapeutic strategies, T-cell modulation, immune priming, innate immunity, and combination therapy. EVIDENCE SYNTHESIS: Prior to the advent of novel agents targeting the vascular endothelial growth factor and mechanistic target of rapamycin pathways, interleukin-2 (IL-2) and interferon-α were the mainstays of RCC treatment. IL-2 remains one of the only treatments capable of curing advanced RCC, albeit in few patients. Despite recent advances, unmet need still exists for patients in the adjuvant setting, those with poor prognostic factors, and those who have progressed on prior targeted therapies. Improved understanding of host-tumor immune interactions has led to development of novel immunotherapeutic agents, including antibodies against immune checkpoint proteins (eg, programmed death-1 and cytotoxic T-lymphocyte antigen-4), and various vaccines. Because many of these compounds are in development, clinical experience with them is limited, although some have demonstrated activity in preliminary studies. CONCLUSIONS: It is not yet clear where these new immunotherapies will fit into RCC treatment paradigms, but they may provide new options for patients whose current choices are limited. Furthermore, predictive biomarkers are needed to identify patients who will derive the greatest benefit from immunotherapy.

Authors
Inman, BA; Harrison, MR; George, DJ
MLA Citation
Inman, BA, Harrison, MR, and George, DJ. "Novel immunotherapeutic strategies in development for renal cell carcinoma." Eur Urol 63.5 (May 2013): 881-889. (Review)
PMID
23084331
Source
pubmed
Published In
European Urology
Volume
63
Issue
5
Publish Date
2013
Start Page
881
End Page
889
DOI
10.1016/j.eururo.2012.10.006

Activity of single-agent bevacizumab in patients with metastatic renal cell carcinoma previously treated with vascular endothelial growth factor tyrosine kinase inhibitors.

PURPOSE: The activity of systemic agents after progression when using vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibition (TKI) and mammalian target of rapamycin (mTOR) inhibition in patients with metastatic renal cell carcinoma (mRCC) is poorly characterized. The anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab has a broad US Food and Drug Administration label and National Comprehensive Cancer Network guideline level 2b recommendation in this setting; we thus explored our institutional experience in this population. METHODS: We conducted a retrospective analysis of patients with mRCC who were treated with bevacizumab in the second- and/or third-line settings; the primary endpoint was progression-free survival (PFS). Overall response rates (ORR), overall survival (OS), and toxicity were analyzed. RESULTS: Twenty-one patients were treated with bevacizumab: the median age was 63 years old; 80% were white and 14% were black; 80% had clear cell histology. All the patients had prior VEGFR TKI therapy; 43% had prior mTOR inhibitor; the median number of prior therapies was 3. The median PFS was 4.4 months (95% CI, 2.8-9.6 months), and the median OS was 19.4 months (95% CI, 9.9-NR months). ORR was 9.5%; 52% of subjects had stable disease as best response, and 52% had disease progression. For subjects treated with prior VEGF and mTOR inhibitors, median PFS and OS were 4.4 and 13.2 months, respectively. Grade 3 to 4 toxicities included fatigue (29%), dehydration (24%), failure to thrive (10%), constipation (10%), and muscle weakness (10%). CONCLUSIONS: Single-agent bevacizumab has acceptable toxicity and moderate disease-stabilizing activity in selected patients with mRCC who have failed prior VEGFR TKI and mTOR inhibitors. These data support clinical benefit to continued ongoing VEGF inhibition. Further prospective studies of bevacizumab alone or with alternative targeted agents in previously treated populations with mRCC are warranted.

Authors
Turnbull, JD; Cobert, J; Jaffe, T; Harrison, MR; George, DJ; Armstrong, AJ
MLA Citation
Turnbull, JD, Cobert, J, Jaffe, T, Harrison, MR, George, DJ, and Armstrong, AJ. "Activity of single-agent bevacizumab in patients with metastatic renal cell carcinoma previously treated with vascular endothelial growth factor tyrosine kinase inhibitors." Clin Genitourin Cancer 11.1 (March 2013): 45-50.
PMID
23041453
Source
pubmed
Published In
Clinical genitourinary cancer
Volume
11
Issue
1
Publish Date
2013
Start Page
45
End Page
50
DOI
10.1016/j.clgc.2012.06.001

Exercise as Treatment for Androgen Deprivation Therapy-Associated Physical Dysfunction: Ready for Prime Time?

Authors
Harrison, MR; Jones, LW
MLA Citation
Harrison, MR, and Jones, LW. "Exercise as Treatment for Androgen Deprivation Therapy-Associated Physical Dysfunction: Ready for Prime Time?." European Urology (2013).
PMID
24315708
Source
scopus
Published In
European Urology
Publish Date
2013

Radium-223 chloride: a potential new treatment for castration-resistant prostate cancer patients with metastatic bone disease.

BACKGROUND: Radium-223 chloride ((223)Ra; Alpharadin) is an alpha-emitting radioisotope that targets areas of osteoblastic metastasis and is excreted by the small intestine. When compared with beta-emitters (eg, strontium-89, samarium-153), (223)Ra delivers a high quantity of energy per track length with short tissue penetration. OBJECTIVE: This review describes the mechanism, radiobiology, and preclinical development of (223)Ra and discusses the clinical data currently available regarding its safety and efficacy profile. METHODS: Data from clinical trials including abstracts were collected and reviewed using the PubMed Database, as well as the American Society of Clinical Oncology abstract database. CONCLUSION: Current bone-targeted therapies fall into two main categories: antiresorptive agents (eg, zoledronic acid, denosumab), which have been shown to delay skeletal-related events, and radiopharmaceuticals (eg, samarium-153), which may have a role in pain palliation. Historically, neither antiresorptive agents nor radiopharmaceuticals have shown definitive evidence of improved overall survival or other antitumor effects in metastatic castrate-resistant prostate cancer (mCRPC). Radiopharmaceuticals are limited by myelosuppresion, thrombocytopenia, and renal excretion. In a recently reported randomized Phase III trial in men with symptomatic bone-metastatic CRPC who had received or were ineligible for docetaxel chemotherapy, (223)Ra treatment resulted in improved overall survival and delayed skeletal-related events. Toxicity consisted of minor gastrointestinal side effects and mild neutropenia and thrombocytopenia that were rarely severe. Pending regulatory approval, (223)Ra may represent a unique and distinct option for an important subgroup of patients with mCRPC; future trials should address its use in combination or in sequence with existing and novel agents.

Authors
Harrison, MR; Wong, TZ; Armstrong, AJ; George, DJ
MLA Citation
Harrison, MR, Wong, TZ, Armstrong, AJ, and George, DJ. "Radium-223 chloride: a potential new treatment for castration-resistant prostate cancer patients with metastatic bone disease." Cancer Manag Res 5 (2013): 1-14.
PMID
23326203
Source
pubmed
Published In
Cancer Manag Res
Volume
5
Publish Date
2013
Start Page
1
End Page
14
DOI
10.2147/CMAR.S25537

A phase 2 study of KX2-391, an oral inhibitor of Src kinase and tubulin polymerization, in men with bone-metastatic castration-resistant prostate cancer

Purpose: KX2-391 is an oral non-ATP-competitive inhibitor of Src kinase and tubulin polymerization. In phase 1 trials, prostate-specific antigen (PSA) declines were seen in patients with advanced prostate cancer. We conducted a single-arm phase 2 study evaluating KX2-391 in men with chemotherapy-naïve bone-metastatic castration-resistant prostate cancer (CRPC). Methods: We treated 31 patients with oral KX2-391 (40 mg twice-daily) until disease progression or unacceptable toxicity. The primary endpoint was 24-week progression-free survival (PFS); a 50 % success rate was pre-defined as clinically significant. Secondary endpoints included PSA progression-free survival (PPFS) and PSA response rates. Exploratory outcomes included pharmacokinetic studies, circulating tumor cell (CTC) enumeration, and analysis of markers of bone resorption [urinary N-telopeptide (uNTx); C-telopeptide (CTx)] and formation [bone alkaline phosphatase (BAP); osteocalcin]. Results: The trial closed early after accrual of 31 patients, due to a pre-specified futility rule. PFS at 24 weeks was 8 %, and median PFS was 18.6 weeks. The PSA response rate (≥30 % decline) was 10 %, and median PPFS was 5.0 weeks. Additionally, 18 % of men with unfavorable (≥5) CTCs at baseline converted to favorable (<5) CTCs with treatment. The proportion of men with declines in bone turnover markers was 32 % for uNTx, 21 % for CTx, 10 % for BAP, and 25 % for osteocalcin. In pharmacokinetic studies, median Cmax was 61 (range 16-129) ng/mL, and median AUC was 156 (35-348) ng h/mL. Common toxicities included hepatic derangements, myelosuppression, fatigue, nausea, and constipation. Conclusion: KX2-391 dosed at 40 mg twice-daily lacks antitumor activity in men with CRPC, but has modest effects on bone turnover markers. Because a Cmax of ≥142 ng/mL is required for tubulin polymerization inhibition (defined from preclinical studies), higher once-daily dosing will be used in future trials. © 2013 Springer-Verlag Berlin Heidelberg.

Authors
Antonarakis, ES; Heath, EI; Posadas, EM; Yu, EY; Harrison, MR; Bruce, JY; Cho, SY; Wilding, GE; Fetterly, GJ; Hangauer, DG; al, E
MLA Citation
Antonarakis, ES, Heath, EI, Posadas, EM, Yu, EY, Harrison, MR, Bruce, JY, Cho, SY, Wilding, GE, Fetterly, GJ, Hangauer, DG, and al, E. "A phase 2 study of KX2-391, an oral inhibitor of Src kinase and tubulin polymerization, in men with bone-metastatic castration-resistant prostate cancer." Cancer Chemotherapy and Pharmacology (2013): 1-10.
PMID
23314737
Source
scival
Published In
Cancer Chemotherapy and Pharmacology
Publish Date
2013
Start Page
1
End Page
10
DOI
10.1007/s00280-013-2079-z

Novel immunotherapeutic strategies in development for renal cell carcinoma

Context: The purpose of this report is to review immunotherapies under investigation for patients with renal cell carcinoma (RCC), the most common form of kidney cancer, for which the incidence and mortality rate continue to increase. Objective: To summarize and evaluate current data on immunotherapies for RCC and discuss issues to be resolved before integration into the RCC treatment paradigm. Evidence acquisition: A search of Medline, clinicaltrials.gov, and congress abstracts/treatment guidelines was performed in May 2012 using the following terms (and variations): metastatic renal cell carcinoma, practice guidelines, response/resistance to current treatments, immunotherapy, novel immunotherapeutic strategies, T-cell modulation, immune priming, innate immunity, and combination therapy. Evidence synthesis: Prior to the advent of novel agents targeting the vascular endothelial growth factor and mechanistic target of rapamycin pathways, interleukin-2 (IL-2) and interferon-α were the mainstays of RCC treatment. IL-2 remains one of the only treatments capable of curing advanced RCC, albeit in few patients. Despite recent advances, unmet need still exists for patients in the adjuvant setting, those with poor prognostic factors, and those who have progressed on prior targeted therapies. Improved understanding of host-tumor immune interactions has led to development of novel immunotherapeutic agents, including antibodies against immune checkpoint proteins (eg, programmed death-1 and cytotoxic T-lymphocyte antigen-4), and various vaccines. Because many of these compounds are in development, clinical experience with them is limited, although some have demonstrated activity in preliminary studies. Conclusions: It is not yet clear where these new immunotherapies will fit into RCC treatment paradigms, but they may provide new options for patients whose current choices are limited. Furthermore, predictive biomarkers are needed to identify patients who will derive the greatest benefit from immunotherapy. © 2012 European Association of Urology.

Authors
Inman, BA; Harrison, MR; George, DJ
MLA Citation
Inman, BA, Harrison, MR, and George, DJ. "Novel immunotherapeutic strategies in development for renal cell carcinoma." European Urology 63.5 (2013): 881-889.
Source
scival
Published In
European Urology
Volume
63
Issue
5
Publish Date
2013
Start Page
881
End Page
889
DOI
10.1016/j.eururo.2012.10.006

A phase 2 study of KX2-391, an oral inhibitor of Src kinase and tubulin polymerization, in men with bone-metastatic castration-resistant prostate cancer

Purpose: KX2-391 is an oral non-ATP-competitive inhibitor of Src kinase and tubulin polymerization. In phase 1 trials, prostate-specific antigen (PSA) declines were seen in patients with advanced prostate cancer. We conducted a single-arm phase 2 study evaluating KX2-391 in men with chemotherapy-naïve bone-metastatic castration-resistant prostate cancer (CRPC). Methods: We treated 31 patients with oral KX2-391 (40 mg twice-daily) until disease progression or unacceptable toxicity. The primary endpoint was 24-week progression-free survival (PFS); a 50 % success rate was pre-defined as clinically significant. Secondary endpoints included PSA progression-free survival (PPFS) and PSA response rates. Exploratory outcomes included pharmacokinetic studies, circulating tumor cell (CTC) enumeration, and analysis of markers of bone resorption [urinary N-telopeptide (uNTx); C-telopeptide (CTx)] and formation [bone alkaline phosphatase (BAP); osteocalcin]. Results: The trial closed early after accrual of 31 patients, due to a pre-specified futility rule. PFS at 24 weeks was 8 %, and median PFS was 18.6 weeks. The PSA response rate (≥30 % decline) was 10 %, and median PPFS was 5.0 weeks. Additionally, 18 % of men with unfavorable (≥5) CTCs at baseline converted to favorable (<5) CTCs with treatment. The proportion of men with declines in bone turnover markers was 32 % for uNTx, 21 % for CTx, 10 % for BAP, and 25 % for osteocalcin. In pharmacokinetic studies, median C max was 61 (range 16-129) ng/mL, and median AUC was 156 (35-348) ng h/mL. Common toxicities included hepatic derangements, myelosuppression, fatigue, nausea, and constipation. Conclusion: KX2-391 dosed at 40 mg twice-daily lacks antitumor activity in men with CRPC, but has modest effects on bone turnover markers. Because a C max of ≥142 ng/mL is required for tubulin polymerization inhibition (defined from preclinical studies), higher once-daily dosing will be used in future trials. © 2013 Springer-Verlag Berlin Heidelberg.

Authors
Antonarakis, ES; Heath, EI; Posadas, EM; Yu, EY; Harrison, MR; Bruce, JY; Cho, SY; Wilding, GE; Fetterly, GJ; Hangauer, DG; Kwan, MFR; Dyster, LM; Carducci, MA
MLA Citation
Antonarakis, ES, Heath, EI, Posadas, EM, Yu, EY, Harrison, MR, Bruce, JY, Cho, SY, Wilding, GE, Fetterly, GJ, Hangauer, DG, Kwan, MFR, Dyster, LM, and Carducci, MA. "A phase 2 study of KX2-391, an oral inhibitor of Src kinase and tubulin polymerization, in men with bone-metastatic castration-resistant prostate cancer." Cancer Chemotherapy and Pharmacology 71.4 (2013): 883-892.
Source
scival
Published In
Cancer Chemotherapy and Pharmacology
Volume
71
Issue
4
Publish Date
2013
Start Page
883
End Page
892
DOI
10.1007/s00280-013-2079-z

Beyond metastatic renal cell carcinoma (mRCC) clinical trials: Targeted therapy use and overall survival in community oncology clinics

Authors
Harrison, MR; George, DJ; Walker, MS; Hudson, LL; Chen, C; Korytowsky, B; Stepanski, EJ; Abernethy, AP
MLA Citation
Harrison, MR, George, DJ, Walker, MS, Hudson, LL, Chen, C, Korytowsky, B, Stepanski, EJ, and Abernethy, AP. "Beyond metastatic renal cell carcinoma (mRCC) clinical trials: Targeted therapy use and overall survival in community oncology clinics." May 20, 2012.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
30
Issue
15
Publish Date
2012

A phase II study of KX2-391, an oral inhibitor of Src kinase and tubulin polymerization, in men with bone-metastatic castration- resistant prostate cancer (CRPC): A PCCTC trial

Authors
Antonarakis, ES; Heath, EI; Posadas, EM; Harrison, MR; Bruce, JY; Yu, EY; Cho, SY; Wilding, GE; Fetterly, GJ; Hangauer, DG; Kwan, M-FR; Dyster, LM; Carducci, MA; Cons, PCCT
MLA Citation
Antonarakis, ES, Heath, EI, Posadas, EM, Harrison, MR, Bruce, JY, Yu, EY, Cho, SY, Wilding, GE, Fetterly, GJ, Hangauer, DG, Kwan, M-FR, Dyster, LM, Carducci, MA, and Cons, PCCT. "A phase II study of KX2-391, an oral inhibitor of Src kinase and tubulin polymerization, in men with bone-metastatic castration- resistant prostate cancer (CRPC): A PCCTC trial." May 20, 2012.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
30
Issue
15
Publish Date
2012

'Real World' treatment of metastatic renal cell carcinoma (mRCC) in community and academic settings

Authors
George, DJ; Walker, MS; Hudson, LL; Chen, C; Korytowsky, B; Harrison, MR; Stepanski, E; Abernethy, AP
MLA Citation
George, DJ, Walker, MS, Hudson, LL, Chen, C, Korytowsky, B, Harrison, MR, Stepanski, E, and Abernethy, AP. "'Real World' treatment of metastatic renal cell carcinoma (mRCC) in community and academic settings." May 2012.
Source
wos-lite
Published In
Bju International
Volume
109
Publish Date
2012
Start Page
5
End Page
5

Activity of single-agent bevacizumab (B) in patients with metastatic renal cell carcinoma (RCC) previously treated with VEGF- and mTOR-based therapies.

Authors
Armstrong, AJ; Turnbull, JD; Cobert, J; Jaffe, T; Harrison, MR; George, DJ
MLA Citation
Armstrong, AJ, Turnbull, JD, Cobert, J, Jaffe, T, Harrison, MR, and George, DJ. "Activity of single-agent bevacizumab (B) in patients with metastatic renal cell carcinoma (RCC) previously treated with VEGF- and mTOR-based therapies." JOURNAL OF CLINICAL ONCOLOGY 30.5 (February 10, 2012).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
30
Issue
5
Publish Date
2012

Outcomes of "real world" treatment for metastatic renal cell carcinoma (mRCC).

Authors
Harrison, MR; George, DJ; Walker, MS; Hudson, LL; Chen, C; Korytowsky, B; Stepanski, EJ; Abernethy, AP
MLA Citation
Harrison, MR, George, DJ, Walker, MS, Hudson, LL, Chen, C, Korytowsky, B, Stepanski, EJ, and Abernethy, AP. "Outcomes of "real world" treatment for metastatic renal cell carcinoma (mRCC)." JOURNAL OF CLINICAL ONCOLOGY 30.5 (February 10, 2012).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
30
Issue
5
Publish Date
2012

Better late than early: FDG-PET imaging in metastatic renal cell carcinoma.

Sunitinib treatment benefits patients with metastatic renal cell carcinoma (mRCC), but response duration can vary widely and resistance is not predicted by standard measures. [¹⁸F]fluoro-2-deoxy-2-D-glucose positron emission tomography (FDG-PET) uptake is variable in mRCC, but changes in FDG-PET uptake may be useful in monitoring disease progression. Further work is needed to personalize treatment for patients with mRCC.

Authors
Harrison, MR; George, DJ
MLA Citation
Harrison, MR, and George, DJ. "Better late than early: FDG-PET imaging in metastatic renal cell carcinoma." Clin Cancer Res 17.18 (September 15, 2011): 5841-5843.
PMID
21926167
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
17
Issue
18
Publish Date
2011
Start Page
5841
End Page
5843
DOI
10.1158/1078-0432.CCR-11-1768

Pharmacotherapy options in advanced renal cell carcinoma: what role for pazopanib?

Over the last 6 years, the treatment of metastatic renal cell carcinoma (mRCC) has undergone dramatic changes. A better understanding of the pathogenesis and tumor biology of sporadic renal cell carcinoma has led to the approval of 6 drug regimens: 3 oral multi-targeted tyrosine-kinase inhibitors (sorafenib, sunitinib, and pazopanib), 2 inhibitors of the mammalian target of rapamycin (temsirolimus and everolimus), and 1 monoclonal antibody against the vascular endothelial growth factor (bevacizumab). Pazopanib, a multi-targeted tyrosine kinase inhibitor that targets VEGFR-1, -2, and-3; PDGFR-α and PDGFR-β, and c-Kit, was approved for the treatment of mRCC in October 2009, several years after the other drugs in its class. The efficacy and safety of pazopanib in Phase I, II, and III trials will be examined and its role in mRCC treatment will be described. Future studies that may clarify pazopanib's role in mRCC will be discussed. Based on pazopanib's demonstrated efficacy in treatment-naïve and cytokine-refractory patients, along with a seemingly favorable toxicity profile compared with other multi-targeted tyrosine-kinase inhibitors, pazopanib may have a unique niche in the armamentarium of treatment options for mRCC. Results from ongoing studies are awaited to confirm pazopanib's favorable efficacy-toxicity ratio, especially in comparison with the previous first-line standard-of-care, sunitinib.

Authors
Harrison, MR
MLA Citation
Harrison, MR. "Pharmacotherapy options in advanced renal cell carcinoma: what role for pazopanib?." Clin Med Insights Oncol 5 (2011): 349-364.
PMID
22174596
Source
pubmed
Published In
Clinical Medicine Insights: Oncology
Volume
5
Publish Date
2011
Start Page
349
End Page
364
DOI
10.4137/CMO.S6087

Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) resistance in metastatic renal cell carcinoma (mRCC): Possible mechanisms and clinical approaches

Introduction: The approvals of sorafenib, sunitinib, and pazopanib have led to increased options for patients with mRCC. Unfortunately, some patients treated with these vascular endothelial growth factor receptor (VEGFR) TKI progress rapidly, while the majority of remaining patients will develop evidence of disease progression within 2 years. Objectives: We gathered preclinical and clinical evidence regarding potential mechanisms of VEGFR TKI resistance and clinical approaches to counter it. Methods: We searched the published medical literature, searching the National Library of Medicine (PubMed) as well as abstracts from annual meetings of the American Society of Clinical Oncology (ASCO) and American Association for Cancer Research (AACR). Results: No clear evidence-based mechanism of VEGFR TKI resistance has been defined to date; therefore, we summarize the existing hypothesisgenerating preclinical, biomarker, and clinical data. Potential mechanisms of resistance to VEGFR TKI include variations in the inherent genetic alterations associated with RCC, independent of VHL. In addition, response to hypoxia induced by VEGFR TKI may drive alternative growth factor mediated angiogenesis. Molecular imaging evidence of early angiogenesis and proliferation rebound following VEGFR TKI exposure suggests progression is still driven by a proangiogenic phenotype. Conclusion: By necessity, clinicians must currently make treatment decisions on the basis of limited data regarding the biology of VEGFR TKI resistance. RCC is a heterogeneous disease from the onset. Understanding the specific genetic profiles of sensitive and resistant subtypes of RCC may aid in both first-line and subsequent treatment selection. In addition, better understanding of tumor response and resistance may lead to novel combination strategies in the future.

Authors
Harrison, MR; George, DJ
MLA Citation
Harrison, MR, and George, DJ. "Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) resistance in metastatic renal cell carcinoma (mRCC): Possible mechanisms and clinical approaches." European journal of Clinical and Medical Oncology 3.4 (2011): 1-9.
Source
scival
Published In
European journal of Clinical and Medical Oncology
Volume
3
Issue
4
Publish Date
2011
Start Page
1
End Page
9

A phase II study of 2-methoxyestradiol (2ME2) NanoCrystal ® dispersion (NCD) in patients with taxane-refractory, metastatic castrate-resistant prostate cancer (CRPC)

Purpose: 2ME2 (Panzem ®) is a non-estrogenic derivative of estradiol with antiproliferative and antiangiogenic activity. Preclinical data support antitumor activity in prostate cancer. This trial evaluated the efficacy of 2ME2 NCD in patients with taxane-refractory, metastatic CRPC. Experimental Design: Patients with metastatic CRPC who had progressed on only one prior taxane-based regimen were eligible. All patients received 2ME2 NCD at 1,500 mg orally four times daily, repeated in 28 day cycles. The primary endpoint was progression-free survival at month 6, with a secondary endpoint of PSA response. An exploratory endpoint was metabolic response on FDG-PET imaging. Results: A total of 50 pts was planned. The study was terminated after 21 pts when a futility analysis showed the primary endpoint was unlikely to be reached. The median number of cycles on study was 2 (range <1 to 12). Adverse events (AE) of grade ≥3 related to the study drug occurred in 7 unique patients (33%): elevations in liver function tests, fatigue or weakness, gastrointestinal hemorrhage, and hyponatremia. Paired FDG-PETscans were obtained for 11 pts. No metabolic responses were observed. Conclusions: 2ME2 NCD did not appear to have clinically significant activity in this study. 2ME2 NCD was well-tolerated and showed some evidence of biologic activity. Given the aggressive biology in this taxane-refractory population, the potential benefit from a cytostatic agent like 2ME2 might better be realized in the pre-chemotherapy (or rising PSA only) stage of CRPC. © Springer Science+Business Media, LLC 2010.

Authors
Harrison, MR; Hahn, NM; Pili, R; Oh, WK; Hammers, H; Sweeney, C; Kim, K; Perlman, S; Arnott, J; Sidor, C; Wilding, G; Liu, G
MLA Citation
Harrison, MR, Hahn, NM, Pili, R, Oh, WK, Hammers, H, Sweeney, C, Kim, K, Perlman, S, Arnott, J, Sidor, C, Wilding, G, and Liu, G. "A phase II study of 2-methoxyestradiol (2ME2) NanoCrystal ® dispersion (NCD) in patients with taxane-refractory, metastatic castrate-resistant prostate cancer (CRPC)." Investigational New Drugs 29.6 (2011): 1465-1474.
PMID
20499131
Source
scival
Published In
Investigational New Drugs
Volume
29
Issue
6
Publish Date
2011
Start Page
1465
End Page
1474
DOI
10.1007/s10637-010-9455-x

Pharmacodynamic study using FLT PET/CT in patients with renal cell cancer and other solid malignancies treated with sunitinib malate

Purpose: To characterize proliferative changes in tumors during the sunitinib malate exposure/withdrawal using 3′-deoxy-3′-[ 18F]fluorothymidine (FLT) positron emission tomography (PET)/computed tomography (CT) imaging. Patients and Methods: Patients with advanced solid malignancies and no prior anti-VEGF exposure were enrolled. All patients had metastatic lesions amenable to FLT PET/CT imaging. Sunitinib was initiated at the standard dose of 50 mg p.o. daily either on a 4/2 or 2/1 schedule. FLT PET/CT scans were obtained at baseline, during sunitinib exposure, and after sunitinib withdrawal within cycle #1 of therapy. VEGF levels and sunitinib pharmacokinetic (PK) data were assessed at the same time points. Results: Sixteen patients (8 patients on 4/2 schedule and 8 patients on 2/1 schedule) completed all three planned FLT PET/CT scans and were evaluable for pharmacodynamic imaging evaluation. During sunitinib withdrawal (change from scans 2 to 3), median FLT PET standardized uptake value (SUV mean) increased +15% (range: -14% to 277%; P = 0.047) for the 4/2 schedule and +19% (range: -5.3% to 200%; P = 0.047) for the 2/1 schedule. Sunitinib PK and VEGF ligand levels increased during sunitinib exposure and returned toward baseline during the treatment withdrawal. Conclusions: The increase of cellular proliferation during sunitinib withdrawal in patients with renal cell carcinoma and other solid malignancies is consistent with a VEGF receptor (VEGFR) tyrosine kinase inhibitor (TKI) withdrawal flare. Univariate and multivariate analysis suggest that plasma VEGF is associated with this flare, with an exploratory analysis implying that patients who experience less clinical benefit have a larger withdrawal flare. This might suggest that patients with a robust compensatory response to VEGFR TKI therapy experience early "angiogenic escape." ©2011 AACR.

Authors
Liu, G; Jeraj, R; Vanderhoek, M; Perlman, S; Kolesar, J; Harrison, M; Simoncic, U; Eickhoff, J; Carmichael, L; Chao, B; Marnocha, R; Ivy, P; Wilding, G
MLA Citation
Liu, G, Jeraj, R, Vanderhoek, M, Perlman, S, Kolesar, J, Harrison, M, Simoncic, U, Eickhoff, J, Carmichael, L, Chao, B, Marnocha, R, Ivy, P, and Wilding, G. "Pharmacodynamic study using FLT PET/CT in patients with renal cell cancer and other solid malignancies treated with sunitinib malate." Clinical Cancer Research 17.24 (2011): 7634-7644.
PMID
22038997
Source
scival
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
17
Issue
24
Publish Date
2011
Start Page
7634
End Page
7644
DOI
10.1158/1078-0432.CCR-11-1677

Pazopanib for the treatment of patients with advanced renal cell carcinoma

Dramatic advances in the care of patients with advanced renal cell carcinoma have occurred over the last ten years, including insights into the molecular pathogenesis of this disease, that have now been translated into paradigm-changing therapeutic strategies. Elucidating the importance of signaling cascades related to angiogenesis is notable among these achievements. Pazopanib is a novel small molecule tyrosine kinase inhibitor that targets VEGFR-1, -2, and -3; PDGFR-α PDGFR-β; and c-kit tyrosine kinases. This agent exhibits a distinct pharmacokinetic profile as well as toxicity profile compared to other agents in the class of VEGF signaling pathway inhibitors. This review will discuss the scientific rationale for the development of pazopanib, as well as preclinical and clinical trials that led to approval of pazopanib for patients with advanced renal cell carcinoma. The most recent information, including data from 2010 national meeting of the American Society of Clinical Oncology, and the design of ongoing Phase III trials, will be discussed. Finally, an algorithm utilizing Level I evidence for the treatment of patients with this disease will be proposed. © the author(s), publisher and licensee Libertas Academica Ltd.

Authors
Lang, JM; Harrison, MR
MLA Citation
Lang, JM, and Harrison, MR. "Pazopanib for the treatment of patients with advanced renal cell carcinoma." Clinical Medicine Insights: Oncology 4 (2010): 95-105.
Source
scival
Published In
Clinical Medicine Insights: Oncology
Volume
4
Publish Date
2010
Start Page
95
End Page
105
DOI
10.4137/CMO.S4088

Response to antiangiogenesis therapy in a patient with advanced adult-type testicular granulosa cell tumor

As granulosa cell tumors of the adult type are extremely uncommon testicular neoplasms, relatively few case reports and case series have been published. Treatment for localized, small-volume, or oligometastatic disease is generally surgical resection alone. Visceral or widely metastatic disease is relatively rare, so there is no consensus approach to treatment. We report the case of an advanced granulosa cell tumor of the testis with a confirmed partial response to an angiogenesis inhibitor after initial resistance to cytotoxic chemotherapy.

Authors
Harrison, MR; Huang, W; Liu, G; Gee, J
MLA Citation
Harrison, MR, Huang, W, Liu, G, and Gee, J. "Response to antiangiogenesis therapy in a patient with advanced adult-type testicular granulosa cell tumor." ONCOLOGY 23.9 (2009).
PMID
19777766
Source
scival
Published In
Oncology
Volume
23
Issue
9
Publish Date
2009

Response to antiangiogenesis therapy in a patient with advanced adult-type testicular granulosa cell tumor.

As granulosa cell tumors of the adult type are extremely uncommon testicular neoplasms, relatively few case reports and case series have been published. Treatment for localized, small-volume, or oligometastatic disease is generally surgical resection alone. Visceral or widely metastatic disease is relatively rare, so there is no consensus approach to treatment. We report the case of an advanced granulosa cell tumor of the testis with a confirmed partial response to an angiogenesis inhibitor after initial resistance to cytotoxic chemotherapy.

Authors
Harrison, MR; Huang, W; Liu, G; Gee, J
MLA Citation
Harrison, MR, Huang, W, Liu, G, and Gee, J. "Response to antiangiogenesis therapy in a patient with advanced adult-type testicular granulosa cell tumor." Oncology (Williston Park, N.Y.) 23.9 (2009): 792-795.
Source
scival
Published In
Oncology
Volume
23
Issue
9
Publish Date
2009
Start Page
792
End Page
795

Beyond taxanes: A review of novel agents that target mitotic tubulin and microtubules, kinases, and kinesins

Until recently, development of chemotherapeutic agents that target mitosis has centered on inhibiting the mitotic spindle through interactions with microtubules. The taxanes, while significantly advancing the treatment of many types of cancer, suffer from problems of hematopoeitic and neurologic toxicities, development of resistance, and an inconvenient formulation. Novel microtubule inhibitors currently in clinical trial and in clinical use have the main advantage of overcoming resistance. Still, they have side effects related to the inhibition of microtubules in normal host cells. Novel antimitotics, which target the mitotic spindle through interactions with nonmicrotubule mitotic mediators like mitotic kinases and kinesins, have been identified and are now in clinical trial. They offer the prospect of surmounting more of the problems inherent with taxanes and the hope of improving upon their broad antitumor efficacy. This review will concentrate on novel agents in later clinical development that target both the spindle microtubule and nonmicrotubule constituents of mitosis.

Authors
Harrison, MR; Holen, KD; Liu, G
MLA Citation
Harrison, MR, Holen, KD, and Liu, G. "Beyond taxanes: A review of novel agents that target mitotic tubulin and microtubules, kinases, and kinesins." Clinical Advances in Hematology and Oncology 7.1 (2009): 54-64.
PMID
19274042
Source
scival
Published In
Clinical advances in hematology & oncology : H&O
Volume
7
Issue
1
Publish Date
2009
Start Page
54
End Page
64
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