Vorinostat in advanced prostate cancer patients progressing on prior chemotherapy (National Cancer Institute Trial 6862): Trial results and interleukin-6 analysis: A study by the Department of Defense Prostate Cancer Clinical Trial Consortium and University of Chicago phase 2 consortium

Deborah Bradley, Dana Rathkopf, Rodney Dunn, Walter M. Stadler, Glenn Liu, David C. Smith, Roberto Pili, James Zwiebel, Howard Scher, Maha Hussain

Research output: Contribution to journalArticle

89 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)5541-5549
Number of pages9
Issue number23
StatePublished - Jan 12 2009


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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