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 Journal Article
| Authors: | Bradley, D.; Rathkopf, D.; Dunn, R.; Stadler, W. M.; Liu, G.; Smith, D. C.; Pili, R.; Zwiebel, J.; Scher, H.; Hussain, M. |
| Article Title: | 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 |
| 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. © 2009 American Cancer Society. |
| Keywords: | adult; clinical article; controlled study; treatment response; aged; aged, 80 and over; middle aged; survival analysis; overall survival; clinical trial; disease course; fatigue; advanced cancer; diarrhea; drug efficacy; drug safety; drug withdrawal; side effect; antineoplastic agents; cancer patient; anorexia; prostate specific antigen; multiple cycle treatment; pain; phase 2 clinical trial; leukopenia; mucosa inflammation; nausea; vomiting; dehydration; weight reduction; creatinine; hemoglobin; creatinine blood level; hemoglobin blood level; drug effect; drug resistance, neoplasm; hematuria; abdominal pain; aspartate aminotransferase blood level; prostate cancer; prostatic neoplasms; aspartate aminotransferase; enzyme inhibitors; thrombosis; androgen antagonists; interleukin 6; vorinostat; muscle weakness; patient compliance; peripheral edema; taste disorder; thrombocyte count; urinary frequency; xerostomia; histone deacetylase inhibitors; hydroxamic acids; interleukin-6 |
| Journal Title: | Cancer |
| Volume: | 115 |
| Issue: | 23 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2009-01-12 |
| Start Page: | 5541 |
| End Page: | 5549 |
| Language: | English |
| DOI: | 10.1002/cncr.24597 |
| PUBMED: | 19711464 |
| PROVIDER: | scopus |
| PMCID: | PMC2917101 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 30 November 2010" - "CODEN: CANCA" - "Source: Scopus" |
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