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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

Department of Medicine and Urology, University of Michigan, Ann Arbor, Michigan, USA.
Cancer (Impact Factor: 4.9). 09/2009; 115(23):5541-9. DOI: 10.1002/cncr.24597
Source: PubMed

ABSTRACT This phase 2 trial was designed to evaluate the efficacy of vorinostat in chemotherapy-pretreated patients with metastatic castration-resistant prostate cancer.
Patients with disease progression on 1 prior chemotherapy, a prostate-specific antigen (PSA) >or=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.
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 >or=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).
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.

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