Department of Medical Oncology, Klinikum Grosshadern, University of Munich, Germany.
BMC Cancer. 2011 Aug 23;11:367. doi: 10.1186/1471-2407-11-367.
Several randomized trials have indicated that combination chemotherapy applied in metastatic colorectal cancer (mCRC) does not significantly improve overall survival when compared to the sequential use of cytotoxic agents (CAIRO, MRC Focus, FFCD 2000-05). The present study investigates the question whether this statement holds true also for bevacizumab-based first-line treatment including escalation- and de-escalation strategies.
METHODS/DESIGN: The AIO KRK 0110/ML22011 trial is a two-arm, multicenter, open-label randomized phase III trial comparing the efficacy and safety of capecitabine plus bevacizumab (Cape-Bev) versus capecitabine plus irinotecan plus bevacizumab (CAPIRI-Bev) in the first-line treatment of metastatic colorectal cancer. Patients with unresectable metastatic colorectal cancer, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, will be assigned in a 1:1 ratio to receive either capecitabine 1250 mg/m(2) bid for 14d (d1-14) plus bevacizumab 7.5 mg/kg (d1) q3w (Arm A) or capecitabine 800 mg/m(2) BID for 14d (d1-14), irinotecan 200 mg/m(2) (d1) and bevacizumab 7.5 mg/kg (d1) q3w (Arm B). Patients included into this trial are required to consent to the analysis of tumour tissue and blood for translational investigations. In Arm A, treatment escalation from Cape-Bev to CAPIRI-Bev is recommended in case of progressive disease (PD). In Arm B, de-escalation from CAPIRI-Bev to Cape-Bev is possible after 6 months of treatment or in case of irinotecan-associated toxicity. Re-escalation to CAPIRI-Bev after PD is possible. The primary endpoint is time to failure of strategy (TFS). Secondary endpoints are overall response rate (ORR), overall survival, progression-free survival, safety and quality of life.
The AIO KRK 0110 trial is designed for patients with disseminated, but asymptomatic mCRC who are not potential candidates for surgical resection of metastasis. Two bevacizumab-based strategies are compared: one starting as single-agent chemotherapy (Cape-Bev) allowing escalation to CAPIRI-Bev and another starting with combination chemotherapy (CAPIRI-Bev) and allowing de-escalation to Cape-Bev and subsequent re-escalation if necessary.
ClinicalTrials.gov Identifier NCT01249638 EudraCT-No.: 2009-013099-38.
几项随机试验表明，与细胞毒性药物（CAIRO、MRC Focus、FFCD 2000-05）的序贯使用相比，转移性结直肠癌（mCRC）中的联合化疗并未显著改善总生存期。本研究探讨了在贝伐珠单抗为基础的一线治疗中，包括递增和递减策略，这一说法是否仍然成立。
方法/设计：AIO KRK 0110/ML22011 试验是一项两臂、多中心、开放标签的随机 III 期试验，比较了转移性结直肠癌一线治疗中卡培他滨联合贝伐珠单抗（Cape-Bev）与卡培他滨联合伊立替康联合贝伐珠单抗（CAPIRI-Bev）的疗效和安全性。无法切除的转移性结直肠癌患者，东部肿瘤协作组（ECOG）体能状态 0-1，将以 1:1 的比例随机分配接受卡培他滨 1250mg/m²bid 14d（d1-14）加贝伐珠单抗 7.5mg/kg（d1）q3w（A 组）或卡培他滨 800mg/m²bid 14d（d1-14），伊立替康 200mg/m²（d1）和贝伐珠单抗 7.5mg/kg（d1）q3w（B 组）。纳入本试验的患者需要同意对肿瘤组织和血液进行转化研究分析。在 A 组中，如果疾病进展（PD），建议从 Cape-Bev 递增至 CAPIRI-Bev。在 B 组中，在治疗 6 个月后或在出现伊立替康相关毒性时，可以从 CAPIRI-Bev 递减至 Cape-Bev。在 PD 后可以再次递增至 CAPIRI-Bev。主要终点是策略失败时间（TFS）。次要终点是总缓解率（ORR）、总生存期、无进展生存期、安全性和生活质量。
AIO KRK 0110 试验适用于有播散但无症状的 mCRC 患者，这些患者不是手术切除转移灶的潜在候选者。比较了两种贝伐珠单抗为基础的策略：一种从单药化疗（Cape-Bev）开始，允许递增至 CAPIRI-Bev，另一种从联合化疗（CAPIRI-Bev）开始，允许递减至 Cape-Bev，并在必要时再次递增。
ClinicalTrials.gov 标识符 NCT01249638 EudraCT-No.：2009-013099-38。
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