Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States of America.
Department of Hematology and Oncology, Massachusetts General Hospital, Boston, MA, United States of America.
Gynecol Oncol. 2019 May;153(2):223-229. doi: 10.1016/j.ygyno.2019.02.004. Epub 2019 Feb 12.
Intraperitoneal (IP) chemotherapy can improve outcomes for women with optimally cytoreduced epithelial ovarian cancer but toxicities are a concern. We conducted 2 phase 2 trials of an IV/IP regimen using carboplatin and paclitaxel without (Trial A) and with bevacizumab (Trial B).
Both trials consisted of carboplatin AUC 6 day 1, and paclitaxel 60 mg/m on days 1,8, 15 of a 21-day cycle; in Trial B, patients received IV bevacizumab 15 mg/kg every cycle starting cycle 2. Chemotherapy was administered IV for cycle 1 and then IP for all subsequent cycles. Primary objectives included safety and tolerability, pathologic CR rate (Trial A), and the rate of completion of IP cycles of therapy (Trial B). Progression-free (PFS), overall survival (OS), and pharmacokinetic analysis were secondary endpoints.
81 patients were treated on both trials (n = 40 and 41 in trials A and B, respectively). Median age for trials A and B was 59 (range, 36-76) and 55 (range, 19-69) years, respectively. 68% and 85% of patients, respectively for A and B, completed at least 4 cycles of treatment in both trials. Treatment with bevacizumab resulted in higher rates of grade 3 fatigue (37 versus 33%) and grade 3-4 diarrhea (22 versus 8%). Median PFS was 23.5 (95%CI 16.2-35.3) and 25 (95%CI 16.4-42.7) months, respectively; median OS was 68 (95%CI 49.5-NR) and 79.7 (95%CI 59.0-79.7) months, respectively for Trial A and B.
Weekly administered IP carboplatin and IP paclitaxel is tolerable and safe with similar activity with and without concommittant bevacizumab in these 2 trials.
腹腔内（IP）化疗可以改善最佳减瘤的上皮性卵巢癌患者的预后，但毒性是一个关注点。我们进行了两项使用卡铂和紫杉醇的 IV/IP 方案的 2 期试验，一项无（试验 A）和一项有贝伐珠单抗（试验 B）。
两项试验均包括卡铂 AUC 6 天 1 次，紫杉醇 60mg/m2，于 21 天周期的第 1、8、15 天；在试验 B 中，患者在第 2 周期开始时每周期接受 IV 贝伐珠单抗 15mg/kg。第 1 周期化疗静脉内给药，然后所有后续周期腹腔内给药。主要目标包括安全性和耐受性、病理完全缓解率（试验 A）和完成腹腔内治疗周期的比率（试验 B）。无进展生存期（PFS）、总生存期（OS）和药代动力学分析是次要终点。
81 名患者在两项试验中接受了治疗（试验 A 和 B 分别为 40 名和 41 名患者）。试验 A 和 B 的中位年龄分别为 59 岁（范围，36-76 岁）和 55 岁（范围，19-69 岁）。分别有 68%和 85%的患者在两项试验中至少完成了 4 个周期的治疗。贝伐珠单抗治疗导致更高的 3 级疲劳（37%比 33%）和 3-4 级腹泻（22%比 8%）发生率。中位 PFS 分别为 23.5 个月（95%CI 16.2-35.3）和 25 个月（95%CI 16.4-42.7），中位 OS 分别为 68 个月（95%CI 49.5-NR）和 79.7 个月（95%CI 59.0-79.7），试验 A 和 B 分别为 68 个月（95%CI 49.5-NR）和 79.7 个月（95%CI 59.0-79.7）。
每周给予 IP 卡铂和 IP 紫杉醇是耐受良好和安全的，在这两项试验中，与同时给予贝伐珠单抗相比，疗效相似。
