Published by Cancer Chemother Pharmacol

M. M. Moore · M. Stockler · R. Lim
T. S. K. Mok · M. Millward · M. J. Boyer

Received: 23 July 2009 / Accepted: 20 December 2009
© Springer-Verlag 2010

Abstract

Purpose

Fenretinide is a synthetic retinoid with activity in prostate cancer and other cell lines.

The aim of this study was to assess the efficacy and tolerability of fenretinide in chemotherapy-naïve men with hormone refractory prostate cancer.

Methods

Eligibility criteria included hormone refractory prostate cancer with a rising PSA at least 6 weeks after peripheral anti-androgen withdrawal, ECOG performance status (PS) 0–1, and no prior chemotherapy. Fenretinide was administered orally at 900 mg m¡2 twice daily for 7 of every 21 days. PSA was measured before each cycle. The primary endpoint was a ¸50% reduction in PSA maintained for at least 3 weeks; secondary endpoints included duration of PSA response, time to treatment failure (TTF: treatment stopped for progression or toxicity) and adverse events (AE).

Results

Twenty seven pts were recruited from 7 centres over 27 months. Median age was 74 (range 49–86), median baseline PSA was 129 (range 19–1,000), and 70% had a PS of 0. The median number of cycles received was 2 (range 0–11) and 20 pts completed at least 1 cycle. One pt (4%) achieved a 50% reduction in PSA lasting 39 days and 15 pts (56%) had not progressed within 6 weeks of starting fenretinide. The median TTF was 54 days (IQR 19–73): 22 (81%) failed with tumour progression, 3 (11%) failed with toxicity and 2 (7%) never commenced the drug. Grade 3 rash occurred in 1 patient, all other AE were grade 1 or 2. The most common AE were nausea (40%), hot Xushes (36%), constipation (32%) and nyctalopia (32%).

Conclusion

High-dose fenretinide had limited antitumour activity in patients with advanced hormone refractory prostate cancer: further evaluation in this setting is not warranted.