Di Bartolomeo Maria, Ciarlo Andrea, Bertolini Alessandro, Barni Sandro, Verusio Claudio, Aitini Enrico, Pietrantonio Filippo, Iacovelli Roberto, Dotti Katia Fiorella, Maggi Claudia, Perrone Federica, Bajetta Emilio
Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Ospedale Misericordia e Dolce, Prato, Italy.
Eur J Cancer. 2015 Mar;51(4):473-481. doi: 10.1016/j.ejca.2014.12.020. Epub 2015 Jan 27.
A dose-finding phase I/II trial that evaluated the maximum tolerated doses of a combination of three drugs with irinotecan, oxaliplatin and capecitabine (COI regimen) has been conducted in patients with metastatic colorectal cancer (mCRC). In this study the safety and activity of the combination of COI regimen plus bevacizumab (COI-B) were assessed.
Patients judged to be unresectable for metastatic disease, were enrolled in a phase II, open-label study and treated with the combination of bevacizumab (5mg/kg on day 1) and COI regimen (irinotecan 180mg/mq on day 1, oxaliplatin 85mg/mq on day 2, capecitabine 2000mg d2-6; q14) as first-line treatment. Induction treatment was administered for a maximum of 8 cycles, followed by maintenance treatment with bevacizumab (7.5mg/kg on d1, q21) until progression.
Fifty-one patients were enrolled in six Italian centres. The primary end-point of overall response rate was met, reaching the value of 62% in the per-protocol population and 57% in the intent-to-treat population, patients with stable disease were also taken into account, the clinical benefit rate was 94%. In the intention-to-treat population, median progression-free and overall survivals were 10.3 and 22 months, respectively. Toxicity was different from 5-fluorouracil-based triplet regimens, with 31% of severe diarrhoea, but a low incidence of grade 3/4 neutropenia (6%) and mucositis (4%).
Our results show the feasibility and promising activity of the combination of capecitabine, oxaliplatin, irinotecan and bevacizumab.
一项剂量探索性I/II期试验评估了三种药物与伊立替康、奥沙利铂和卡培他滨联合使用（COI方案）的最大耐受剂量，该试验已在转移性结直肠癌（mCRC）患者中开展。本研究评估了COI方案联合贝伐单抗（COI-B）的安全性和活性。
判定为转移性疾病不可切除的患者参加了一项II期开放标签研究，接受贝伐单抗（第1天5mg/kg）和COI方案（第1天伊立替康180mg/m²，第2天奥沙利铂85mg/m²，卡培他滨2000mg第2 - 6天；每14天一次）联合治疗作为一线治疗。诱导治疗最多进行8个周期，随后用贝伐单抗（第1天7.5mg/kg，每21天一次）进行维持治疗直至疾病进展。
51名患者在六个意大利中心入组。达到了总缓解率这一主要终点，符合方案人群中的缓解率为62%，意向性治疗人群中的缓解率为57%，稳定疾病患者也被纳入计算，临床获益率为94%。在意向性治疗人群中，无进展生存期和总生存期的中位数分别为10.3个月和22个月。毒性与基于5-氟尿嘧啶的三联方案不同，严重腹泻发生率为31%，但3/4级中性粒细胞减少（6%）和黏膜炎（4%）的发生率较低。
我们的结果显示了卡培他滨、奥沙利铂、伊立替康和贝伐单抗联合使用的可行性和有前景的活性。
