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Vorinostat in advanced prostate cancer patients progressing on prior chemotherapy (National Cancer Institute Trial 6862)
Author(s) -
Bradley Deborah,
Rathkopf Dana,
Dunn Rodney,
Stadler Walter M.,
Liu Glenn,
Smith David C.,
Pili Roberto,
Zwiebel James,
Scher Howard,
Hussain Maha
Publication year - 2009
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.24597
Subject(s) - medicine , adverse effect , prostate cancer , nausea , clinical endpoint , vorinostat , chemotherapy , vomiting , cancer , oncology , surgery , gastroenterology , clinical trial , histone deacetylase , biochemistry , chemistry , gene , histone
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.