Division of Gynecologic Oncology, Cleveland Clinic and MetroHealth Medical Center, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Gynecol Oncol. 2011 Jan;120(1):38-42. doi: 10.1016/j.ygyno.2010.10.011. Epub 2010 Nov 5.
To evaluate clinical activity of weekly topotecan plus carboplatin in patients with platinum-sensitive recurrent ovarian, fallopian tube, or peritoneal carcinoma.
An open-label, single-arm, multicenter Phase I/II study. Phase II was the activity assessment phase, with overall response rate (ORR) as the primary endpoint. Eligible patients (females aged ≥18 years) received study treatment at the maximum-tolerated dose (MTD) identified in Phase I: intravenous topotecan 2.5mg/m(2) (Days 1 and 8), followed by carboplatin AUC 5 (Day 1), every 21 days. A two-stage Green-Dahlberg design was used to assess efficacy of treatment. An ORR of ≤30% was required to conclude that treatment was ineffective.
Twenty-two patients in Phase I permitted identification of the MTD. In Phase II, 55 patients (median age 64.0 years) were enrolled and included in the intent-to-treat population. There were six complete responses (10.9%) and 11 partial responses (20.0%), giving an ORR of 30.9% (17 patients; 95% CI: 18.7%, 43.1%). Median time to response and progression-free survival were 6.57 weeks (95% CI: 5.86, 12.57) and 44.29 weeks (95% CI: 36.14, 52.14), respectively. Grade 3/4 hematological toxicity caused dose reductions, treatment delays and study discontinuation. Neutropenia (Grade 3: 29%; Grade 4: 11%) was the most common hematological adverse event (AE). Fatigue (71%) and nausea (71%) were the most common drug-related non-hematologic AEs.
This study showed an acceptable benefit-risk profile for topotecan plus carboplatin. Further studies using alternative dose levels could help define an optimal dosing schedule for this treatment combination in patients with platinum-sensitive recurrent disease.
评估每周拓扑替康联合卡铂治疗铂类敏感复发性卵巢、输卵管或腹膜癌患者的临床疗效。
这是一项开放标签、单臂、多中心的 I/II 期研究。II 期为疗效评估阶段，总缓解率（ORR）为主要终点。符合条件的患者（年龄≥18 岁的女性）接受 I 期确定的最大耐受剂量（MTD）治疗：静脉注射拓扑替康 2.5mg/m2（第 1 和 8 天），随后卡铂 AUC 5（第 1 天），每 21 天一次。采用两阶段 Green-Dahlberg 设计评估治疗效果。如果治疗无效，则要求 ORR≤30%。
I 期有 22 例患者，允许确定 MTD。II 期共入组 55 例患者（中位年龄 64.0 岁），并纳入意向治疗人群。6 例患者完全缓解（10.9%），11 例部分缓解（20.0%），总缓解率为 30.9%（17 例；95%CI：18.7%，43.1%）。中位缓解时间和无进展生存期分别为 6.57 周（95%CI：5.86，12.57）和 44.29 周（95%CI：36.14，52.14）。3/4 级血液学毒性导致剂量减少、治疗延迟和研究中止。中性粒细胞减少症（3 级：29%；4 级：11%）是最常见的血液学不良事件（AE）。疲乏（71%）和恶心（71%）是最常见的药物相关非血液学不良事件。
该研究显示拓扑替康联合卡铂的获益风险比可接受。使用替代剂量水平的进一步研究可能有助于确定该治疗方案在铂类敏感复发性疾病患者中的最佳剂量方案。
