Vorinostat in advanced prostate cancer patients progressing on prior chemotherapy (National Cancer Institute Trial 6862)
Bradley, Deborah; Rathkopf, Dana; Dunn, Rodney L.; Stadler, Walter M.; Liu, Glenn; Smith, David C.; Pili, Roberto; Zwiebel, James; Scher, Howard; Hussain, Maha H. A.
2009-12-01
Citation
Bradley, Deborah; Rathkopf, Dana; Dunn, Rodney; Stadler, Walter M.; Liu, Glenn; Smith, David C.; Pili, Roberto; Zwiebel, James; Scher, Howard; Hussain, Maha (2009). "Vorinostat in advanced prostate cancer patients progressing on prior chemotherapy (National Cancer Institute Trial 6862) This study was presented in part at the 2008 American Society of Clinical Oncology Genitourinary Cancers Symposium, San Francisco, California, February 14-16, 2008. Authors of the Department of Defense Prostate Cancer Clinical Trial Consortium and University of Chicago Phase 2 Consortium also included George Wilding, MD, 4 Susan Slovin, MD, PhD, 2 Kathleen A. Cooney, MD, 1 June Escara-Wilke, MS, 1 and Evan Keller, DVM, PhD. 1 ." Cancer 115(23): 5541-5549. <http://hdl.handle.net/2027.42/64445>
Abstract
BACKGROUND: This phase 2 trial was designed to evaluate the efficacy of vorinostat in chemotherapy-pretreated patients with metastatic castration-resistant prostate cancer. METHODS: Patients with disease progression on 1 prior chemotherapy, a prostate-specific antigen (PSA) ≥5 ng/mL, and adequate organ function were treated with 400 mg vorinostat orally daily. The primary endpoint was the 6-month progression rate. Secondary endpoints included safety, rate of PSA decline, objective response, overall survival, and effects of vorinostat on serum interleukin-6 (IL-6) levels. RESULTS: Twenty-seven eligible patients were accrued. The median number of cycles delivered was 2 (range, 1-7). All patients were taken off therapy before 6 months. The best objective response in the eligible patient was stable disease in 2 (7%) patients. No PSA decline of ≥50% was observed. There was 1 grade 4 adverse event (AE), and 44% of patients experienced grade 3 adverse events. The most common adverse events were fatigue (81%), nausea (74%), anorexia (59%), vomiting (33%), diarrhea (33%), and weight loss (26%). Median time to progression and overall survival were 2.8 and 11.7 months, respectively. Median IL-6 levels (pg/mL) were higher in patients removed from the protocol for toxicity compared with progression at all time points, including baseline (5.2 vs 2.1, P = .02), Day 15 Cycle 1 (9.5 vs 2.2, P = .01), Day 1 Cycle 2 (9.8 vs 2.2, P = .01), and end of study (11.0 vs 2.9, P = .09). CONCLUSIONS: Vorinostat at this dose was associated with significant toxicities limiting efficacy assessment in this patient population. The significant association between IL-6 levels and removal from the study for toxicities warrants further investigation. Cancer 2009. © 2009 American Cancer Society.Publisher
Wiley Subscription Services, Inc., A Wiley Company
ISSN
0008-543X 1097-0142
Other DOIs
PMID
19711464
Types
Article
URI
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=19711464&dopt=citationMetadata
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