Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: Results from the BICC-C study
Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: Results from the BICC-C study
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DOI：
10.1200/jco.2007.11.3357
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发表时间：
2007-10-20
影响因子：
45.3
通讯作者：
Barrueco, Jose
中科院分区：
文献类型：
--
作者：
Fuchs, Charles S.;Marshall, John;Barrueco, Jose
目的本III期研究比较了以下三种不同的含伊立替康方案在转移性结直肠癌一线治疗中的安全性和疗效：伊立替康+输注氟尿嘧啶（FU）/亚叶酸（LV）（FOLFIRI），伊立替康+推注FU/LV（mIFL），和伊立替康+口服卡培他滨（CapeIRI）患者和方法将430例既往未接受治疗的转移性结直肠癌患者随机分为FOLFIRI组（n = 144）、mIFL组（n = 141）和CapeIRI组（n = 145）。患者同时被随机分配到塞来昔布或安慰剂的双盲治疗。方案修订后，另外117例患者被随机分配至FOLFIRI+贝伐珠单抗组（FOLFIRI Bev; n = 57）或mILF+贝伐珠单抗组（mIFL = Bev; n = 60），而CapeIRI组被中止。主要研究终点为无进展生存期（PFS），次要终点为总生存期（OS）、反应率和毒性。结果FOLFIRI组中位PFS为7.6个月，mIFL组为5.9个月（与FOLFIRI组比较P = 0.004），CapeIRI组为5.8个月（P = 0.015）。FOLFIRI组的中位OS为23.1个月，mIFL组为17.6个月（P = 0.09），CapeIRI组为18.9个月（P = 0.27）。CapeIRI与严重呕吐、腹泻和脱水的发生率较高相关。在添加贝伐珠单抗的修正案后，FOLFIRI+Bev的中位生存时间尚未达到，mIFL+Bev的中位生存时间为19.2个月（P = .007）。FOLFIRI+Bev与≥ 3级高血压的发生率相关性高于mIFL+Bev。结论FOLFIRI和FOLFIRI+Bev具有上级活性，且安全性较高。FU输注方案应是转移性结直肠癌一线治疗的首选伊立替康方案。
Purpose This phase III study compared the safety and efficacy of the following three different irinotecan-containing regimens in the first-line treatment of metastatic colorectal cancer: irinotecan plus infusional fluorouracil (FU)/leucovorin (LV) (FOLFIRI), irinotecan plus bolus FU/LV (mIFL), and irinotecan plus oral capecitabine (CapeIRI).Patients and Methods A total of 430 previously untreated metastatic colorectal cancer patients were randomly assigned to receive FOLFIRI (n = 144), mIFL (n = 141), or CapeIRI (n = 145). Patients were concurrently randomly assigned to a double-blind treatment with celecoxib or placebo. After a protocol amendment, an additional 117 patients were randomly assigned to either FOLFIRI plus bevacizumab (FOLFIRI Bev; n = 57) or mILF plus bevacizumab (mIFL = Bev; n = 60), whereas the CapeIRI arm was discontinued. The primary study end point was progression-free survival (PFS), with secondary end points of overall survival (OS), response rate, and toxicity.Results Median PFS was 7.6 months for FOLFIRI, 5.9 months for mIFL (P = .004 for the comparison with FOLFIRI), and 5.8 months for CapeIRI (P = .015). Median OS was 23.1 months for FOLFIRI, 17.6 months for mIFL (P = .09), and 18.9 months for CapeIRI (P = .27). CapeIRI was associated with higher rates of severe vomiting, diarrhea, and dehydration. After the amendment to add bevacizumab, the median survival time has not yet been reached for FOLFIRI+Bev and was 19.2 months for mIFL+Bev (P = .007). FOLFIRI+Bev was associated with a higher rate of >= grade 3 hypertension than mIFL+Bev.Conclusion FOLFIRI and FOLFIRI+Bev offered superior activity to their comparators and were comparably safe. An infusional schedule of FU should be the preferred irinotecan-based regimen in first-line metastatic colorectal cancer.