Lessons learned: Temsirolimus maintenance therapy after docetaxel induction chemotherapyis safe in patients with castration-resistant prostate cancer, although biochemical or tumor responses are rare;does not diminish quality of life; anddelays radiological and/or symptomatic progression by approximately 6 months.
Background: No standard therapy is available for men with castration-resistant prostate cancer (CRPC) who have responded to docetaxel and do not yet have disease progression. Hence, we designed a single-arm phase II trial to explore whether the mTOR inhibitor temsirolimus can maintain the response to docetaxel without compromising quality of life.
Methods: After successful docetaxel induction (75 mg/m(2) every 3 weeks; 6-10 cycles), 21 CRPC patients underwent temsirolimus maintenance treatment (25 mg weekly; 4 weeks per cycle). The primary endpoint was the time to treatment failure (TTTF) (i.e., radiological and/or symptomatic progression). The secondary endpoints included the tumor response rate (RECIST 1.0), safety (National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0), quality of life (Functional Assessment of Cancer Therapy-Prostate [FACT-P]), pain (Present Pain Intensity [PPI] scale), prostate-specific antigen (PSA) parameters, including time to PSA progression (TTPP) according to Prostate Cancer Clinical Trials Working Group criteria, and serial enumeration of circulating endothelial cells (CECs) and endothelial progenitor cells (CEPs).
Results: Patients received a median of 7 cycles of temsirolimus (range, 1-28), resulting in a median TTTF of 24.3 weeks (95% confidence interval [CI], 16.1-33.0), 1 partial tumor response (4.8%), 1 PSA response (4.8%), and a median TTPP of 12.2 weeks (95% CI, 7.8-23.9). Grade 3-4 adverse events were infrequent, and FACT-P and PPI scores remained stable during treatment. CECs did not predict clinical benefit, and CEPs were not consistently detectable.
Conclusion: Temsirolimus maintenance therapy after successful docetaxel induction is feasible, does not adversely affect quality of life, and, in this exploratory single-arm phase II study, resulted in a median TTTF of 24.3 weeks.
经验
替西罗莫司用于多西他赛诱导化疗后的维持治疗
• 可安全地用于去势难治性前列腺癌患者,尽管生物化学或肿瘤缓解罕见;
• 不会损害生活质量,并且
• 可使放射学和(或)症状性进展推迟约6个月。
摘要
背景. 对于多西他赛治疗有效且尚未发生疾病进展的去势难治性前列腺癌(CRPC)男性患者,目前尚无标准治疗。因此我们设计了一项单臂II期临床试验,旨在探索mTOR抑制剂替西罗莫司能否维持多西他赛的疗效而不损害患者生活质量。
方法. 21例CRPC患者在多西他赛诱导(75 mg/m2每3周一次,6 ∼ 10周期)治疗成功后接受了替西罗莫司维持治疗(25 mg每周一次,每周期4周)。主要终点为至治疗失败时间(TTTF)[即放射学和(或)症状性进展]。次要终点包括肿瘤缓解率(RECIST 1.0)、安全性(美国国家癌症研究所常见不良反应事件评价标准3.0版本)、生活质量[前列腺癌治疗功能评价(FACT-P)]、疼痛[现时疼痛强度(PPI)量表],以及前列腺特异性抗原(PSA)参数,包括依据前列腺癌临床试验工作组标准判定的至PSA进展时间(TTPP)以及循环内皮细胞(CEC)和内皮祖细胞(CEP)的连续计数。
结果. 替西罗莫司中位治疗周期为7周期(范围1 ∼ 28),中位TTTF为24.3周[95%置信区间(CI):16.1 ∼ 33.0],1例肿瘤部分缓解(4.8%)、1例PSA缓解(4.8%),中位TTPP为12.2周(95%CI:7.8 ∼ 23.9)。治疗期间3/4级不良事件少见,且FACT-P和PPI评分保持稳定。CEC不能预测临床获益,CEP不能持续检出。
结论. 多西他赛诱导治疗成功后使用替西罗莫司维持治疗可行且不损害生活质量。本项探索性II期单臂研究中达到了24.3周的中位TTTF。The Oncologist 2015;20:1351–1352
©AlphaMed Press; the data published online to support this summary is the property of the authors.