Rosenberg Jonathan E, Weinberg Vivian K, Kelly W Kevin, Michaelson Dror, Hussain Maha H, Wilding George, Gross Mitchell, Hutcheon Douglass, Small Eric J
Department of Medicine, University of California at San Francisco, Comprehensive Cancer Center, San Francisco, California, USA.
Cancer. 2007 Aug 1;110(3):556-63. doi: 10.1002/cncr.22811.
This randomized, noncomparative, multicenter, clinical trial evaluated ixabepilone or mitoxantrone/prednisone (MP) as second-line chemotherapy for taxane-refractory, hormone-refractory, prostate cancer (HRPC).
Patients with HRPC that progressed during or within 60 days of cessation of taxane chemotherapy were randomly selected with equal probability to ixabepilone 35 mg/m(2) intravenously every 3 weeks, or mitoxantrone 14 mg/m(2) intravenously every 3 weeks and prednisone 5 mg orally twice daily. Treatment continued until progression or toxicity; crossover was allowed.
Forty-one patients were accrued to each arm of the study. The median number of cycles administered for each arm was 3. Median survival from protocol entry was 10.4 months with ixabepilone and 9.8 months with MP. Prostate-specific antigen (PSA) declines of >or=50% were observed in 17% of ixabepilone (95% CI, 7-32) and 20% of second-line MP patients (95% CI, 9-35). Partial responses were observed in 1 of 24 ixabepilone and in 2 of 21 MP patients with evaluable measurable disease. Median duration of second-line ixabepilone and MP treatment was 2.2 months and 2.3 months, respectively. For third-line crossover treatment, PSA declines of >or=50% were observed in 3 of 27 ixabepilone-treated and 4 of 15 MP-treated patients. Prior taxane response was associated with an increased likelihood of second-line ixabepilone or MP response. Low baseline lactate dehydrogenase and absence of visceral metastases independently predicted improved survival. The most common grade 3/4 toxicity associated with second-line treatment was neutropenia (54% of ixabepilone patients and 63% of MP patients).
Ixabepilone and MP had modest activity as second-line chemotherapy for docetaxel-refractory HRPC. The median survival for the entire cohort treated in this study was 9.8 months.
本随机、非对照、多中心临床试验评估了伊沙匹隆或米托蒽醌/泼尼松（MP）作为紫杉烷难治性、激素难治性前列腺癌（HRPC）的二线化疗方案。
在紫杉烷化疗期间或停药后60天内病情进展的HRPC患者，以相等的概率随机选择接受每3周静脉注射35mg/m²伊沙匹隆，或每3周静脉注射14mg/m²米托蒽醌及每日口服2次5mg泼尼松。治疗持续至病情进展或出现毒性反应；允许交叉治疗。
研究的每个治疗组纳入了41例患者。每个治疗组的中位给药周期数为3个。从进入方案开始计算，伊沙匹隆组的中位生存期为10.4个月，MP组为9.8个月。伊沙匹隆组17%（95%CI，7 - 32）和二线MP组20%（95%CI，9 - 35）的患者前列腺特异性抗原（PSA）下降≥50%。在可评估可测量疾病的24例伊沙匹隆患者中有1例出现部分缓解，21例MP患者中有2例出现部分缓解。二线伊沙匹隆和MP治疗的中位持续时间分别为2.2个月和2.3个月。对于三线交叉治疗，接受伊沙匹隆治疗的27例患者中有3例、接受MP治疗的15例患者中有4例PSA下降≥50%。既往紫杉烷治疗反应与二线伊沙匹隆或MP治疗反应的可能性增加相关。低基线乳酸脱氢酶水平和无内脏转移独立预测生存期改善。与二线治疗相关的最常见3/4级毒性反应是中性粒细胞减少（伊沙匹隆组患者的54%和MP组患者的63%）。
伊沙匹隆和MP作为多西他赛难治性HRPC的二线化疗方案活性中等。本研究中治疗的整个队列的中位生存期为9.8个月。
