芬维 A 酯治疗激素难治性前列腺癌的Ⅱ期临床研究：癌症治疗研究组的一项试验。

A phase II study of fenretinide in patients with hormone refractory prostate cancer: a trial of the Cancer Therapeutics Research Group.

机构信息

Sydney Cancer Centre, Hospital Rd, Concord, NSW, 2139, Australia.

出版信息

Cancer Chemother Pharmacol. 2010 Oct;66(5):845-50. doi: 10.1007/s00280-009-1228-x. Epub 2010 Jan 16.

DOI:10.1007/s00280-009-1228-x

PMID:20082080

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 > or =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 flushes (36%), constipation (32%) and nyctalopia (32%).

CONCLUSION

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

摘要

目的

芬维 A 酯是一种合成维 A 酸，对前列腺癌和其他细胞系具有活性。本研究旨在评估芬维 A 酯在激素难治性前列腺癌患者中的疗效和耐受性。

方法

入选标准包括外周抗雄激素撤药 6 周后 PSA 升高的激素难治性前列腺癌、ECOG 表现状态（PS）0-1 和无既往化疗。芬维 A 酯口服，每日 2 次，每次 900mg/m2，每 21 天连用 7 天。每个周期前测量 PSA。主要终点是 PSA 下降≥50%，持续至少 3 周；次要终点包括 PSA 缓解持续时间、治疗失败时间（TTF：因进展或毒性而停止治疗）和不良事件（AE）。

结果

27 例患者在 27 个月内在 7 个中心入组。中位年龄为 74 岁（范围 49-86 岁），中位基线 PSA 为 129（范围 19-1000），70%的 PS 为 0。中位接受的周期数为 2（范围 0-11），20 例患者至少完成了 1 个周期。1 例（4%）患者 PSA 下降≥50%，持续 39 天，15 例（56%）患者在开始芬维 A 酯后 6 周内未进展。中位 TTF 为 54 天（IQR 19-73）：22 例（81%）因肿瘤进展而失败，3 例（11%）因毒性而失败，2 例（7%）从未开始使用药物。1 例患者出现 3 级皮疹，其他 AE 均为 1 级或 2 级。最常见的 AE 是恶心（40%）、热潮红（36%）、便秘（32%）和夜间视力障碍（32%）。