Eisenhauer Eric L, Zanagnolo Vanna, Cohn David E, Salani Ritu, O'Malley David M, Sutton Gregory, Callahan Michael J, Cobb Bobbi, Fowler Jeffrey M, Copeland Larry J
Division of Gynecologic Oncology, The Ohio State University College of Medicine, Columbus, OH, USA.
Division of Gynaecology, European Institute of Oncology, Milano, Italy.
Gynecol Oncol. 2014 Aug;134(2):262-6. doi: 10.1016/j.ygyno.2014.05.030. Epub 2014 Jun 5.
The doublet gemcitabine and carboplatin is effective for the treatment of recurrent ovarian cancer, while multi-agent chemotherapy with bevacizumab may add additional benefit. This phase II study tested the efficacy and safety of a biweekly gemcitabine, carboplatin, and bevacizumab combination in patients with platinum-sensitive recurrent ovarian, peritoneal, or tubal cancer (ROC).
Eligible patients received concurrent gemcitabine 1000 mg/m(2), carboplatin area under the curve 3, and bevacizumab 10 mg/kg administered intravenously on days 1 and 15 every 28 days for six cycles or up to 24 cycles if clinical benefit occurred. The primary end points were progression-free survival (PFS) by RECIST, and safety; the secondary end points were objective response rates and overall survival.
Overall, 45 patients were enrolled. The median PFS was 13.3 months (95% CI, 11.3 to 15.3). The objective response rate was 69%. Grade 4 hematologic toxicities included neutropenia (27%) and thrombocytopenia (2%). Grades 3 and 4 non-hematologic toxicities included fatigue (18%), pain (9%), and nausea/vomiting (4%). There were 2 episodes of cerebrovascular accidents, 2 noted DVTs, and no episodes of bowel perforation. Median OS was 36.1 months (95% CI, 26.7 to 45.5).
Biweekly gemcitabine, carboplatin, and bevacizumab were an effective regimen in recurrent ovarian cancer, with comparable toxicity to recently reported day 1 gemcitabine, carboplatin, bevacizumab, and day 8 gemcitabine. Response rate and PFS are improved from reported outcomes of the gemcitabine carboplatin doublet. The degree to which biweekly dosing may present a more rationale schedule for this triplet should be evaluated further.
吉西他滨与卡铂联合方案对复发性卵巢癌有效，而贝伐单抗联合多药化疗可能会带来额外益处。这项II期研究测试了每两周一次的吉西他滨、卡铂和贝伐单抗联合方案在铂敏感的复发性卵巢、腹膜或输卵管癌（ROC）患者中的疗效和安全性。
符合条件的患者每28天在第1天和第15天接受静脉注射吉西他滨1000mg/m²、曲线下面积为3的卡铂以及10mg/kg贝伐单抗，共六个周期；若出现临床获益则最多进行24个周期。主要终点为根据RECIST标准评估的无进展生存期（PFS）和安全性；次要终点为客观缓解率和总生存期。
总共入组了45例患者。中位PFS为13.3个月（95%CI，11.3至15.3）。客观缓解率为69%。4级血液学毒性包括中性粒细胞减少（27%）和血小板减少（2%）。3级和4级非血液学毒性包括疲劳（18%）、疼痛（9%）以及恶心/呕吐（4%）。发生了2次脑血管意外事件，2例深静脉血栓形成，未发生肠穿孔事件。中位总生存期为36.1个月（95%CI，26.7至45.5）。
每两周一次的吉西他滨、卡铂和贝伐单抗联合方案对复发性卵巢癌是一种有效的治疗方案，其毒性与最近报道的第1天使用吉西他滨、卡铂、贝伐单抗以及第8天使用吉西他滨的方案相当。缓解率和PFS较吉西他滨-卡铂双联方案的报道结果有所改善。每两周给药一次对该三联方案而言是否更具合理性，这一问题有待进一步评估。
