Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston.
Divisions of Medical Oncology and Urology, Duke University Medical Center, Durham.
Ann Oncol. 2012 Mar;23(3):688-694. doi: 10.1093/annonc/mdr349. Epub 2011 Aug 5.
This phase 1/2 study assessed sunitinib combined with docetaxel (Taxotere) and prednisone in chemotherapy-naive metastatic, castration-resistant prostate cancer (mCRPC) patients.
To determine the recommended phase 2 dose (RP2D), 25 patients in four dose escalation cohorts received 3-week cycles of sunitinib (2 weeks on, 1 week off), docetaxel and prednisone, preceded by a 4-week sunitinib 50 mg/day lead in. RP2D was evaluated in 55 additional patients. The primary end point was prostate-specific antigen (PSA) response rate.
One phase 1 dose-limiting toxicity occurred (grade 3 hyponatremia). The RP2D was sunitinib 37.5 mg/day, docetaxel 75 mg/m(2) and prednisone 5 mg b.i.d. During phase 2, confirmed PSA responses occurred in 31 patients [56.4% (95% confidence interval 42.3-69.7)]. Median time to PSA progression was 9.8 months. Forty-one patients (75%) were treated >3 months, 12 (22%) completed the study (16 cycles) and 43 (78%) discontinued (36% for disease progression and 27% adverse events). The most frequent treatment-related grade 3/4 adverse events were neutropenia (53%; 15% febrile) and fatigue/asthenia (16%). Among 33 assessable patients, 14 (42.4%) had confirmed partial response. Median progression-free and overall survivals were 12.6 and 21.7 months, respectively.
This combination was moderately well tolerated, with promising response rate and survival benefit, justifying further investigation in mCRPC.
这项 1/2 期研究评估了舒尼替尼联合多西他赛（泰索帝）和泼尼松在初次化疗的转移性去势抵抗性前列腺癌（mCRPC）患者中的疗效。
为了确定推荐的 2 期剂量（RP2D），25 名患者被分为 4 个剂量递增组，接受舒尼替尼（2 周用药，1 周停药）、多西他赛和泼尼松治疗，在此之前先进行为期 4 周的舒尼替尼 50mg/天的导入治疗。另外 55 名患者接受了 RP2D 治疗。主要终点为前列腺特异性抗原（PSA）反应率。
1 例出现 1 期剂量限制毒性（3 级低钠血症）。RP2D 为舒尼替尼 37.5mg/天，多西他赛 75mg/m2，泼尼松 5mg bid。在 2 期研究中，31 名患者（56.4%[95%置信区间 42.3-69.7]）确证 PSA 有反应。PSA 进展中位时间为 9.8 个月。41 名患者（75%）接受治疗>3 个月，12 名（22%）完成研究（16 个周期），43 名（78%）停药（36%因疾病进展，27%因不良事件）。最常见的治疗相关 3/4 级不良事件为中性粒细胞减少（53%；15%为发热性）和疲乏/无力（16%）。在 33 名可评估患者中，14 名（42.4%）确证有部分缓解。中位无进展生存期和总生存期分别为 12.6 个月和 21.7 个月。
该联合方案具有较好的耐受性，反应率和生存获益有前景，因此值得进一步研究在 mCRPC 中的应用。
