一项比较伊立替康、亚叶酸钙和氟尿嘧啶与亚叶酸钙和氟尿嘧啶辅助化疗用于 II 期和 III 期结肠癌的随机 III 期试验：希腊肿瘤协作组研究。
A randomized phase III trial of adjuvant chemotherapy with irinotecan, leucovorin and fluorouracil versus leucovorin and fluorouracil for stage II and III colon cancer: a Hellenic Cooperative Oncology Group study.
机构信息
Department of Clinical Therapeutics, Alexandra Hospital, University of Athens School of Medicine, Athens, Greece.
出版信息
BMC Med. 2011 Jan 31;9:10. doi: 10.1186/1741-7015-9-10.
BACKGROUND
Colon cancer is a public health problem worldwide. Adjuvant chemotherapy after surgical resection for stage III colon cancer has been shown to improve both progression-free and overall survival, and is currently recommended as standard therapy. However, its value for patients with stage II disease remains controversial. When this study was designed 5-fluorouracil (5FU) plus leucovorin (LV) was standard adjuvant treatment for colon cancer. Irinotecan (CPT-11) is a topoisomerase I inhibitor with activity in metastatic disease. In this multicenter adjuvant phase III trial, we evaluated the addition of irinotecan to weekly 5FU plus LV in patients with stage II or III colon cancer.
METHODS
The study included 873 eligible patients. The treatment consisted of weekly administration of irinotecan 80 mg/m2 intravenously (i.v.), LV 200 mg/m2 and 5FU 450 mg/m2 bolus (Arm A) versus LV 200 mg/m2 and 5FU 500 mg/m2 i.v. bolus (Arm B). In Arm A, treatments were administered weekly for four consecutive weeks, followed by a two-week rest, for a total of six cycles, while in Arm B treatments were administered weekly for six consecutive weeks, followed by a two-week rest, for a total of four cycles. The primary end-point was disease-free survival (DFS) at three years.
RESULTS
The probability of overall survival (OS) at three years was 0.88 for patients in Arm A and 0.86 for those in Arm B, while the five-year OS probability was 0.78 and 0.76 for patients in Arm A and Arm B, respectively (P = 0.436). Furthermore, the probability of DFS at three years was 0.78 and 0.76 for patients in Arm A and Arm B, respectively (P = 0.334). With the exception of leucopenia and neutropenia, which were higher in patients in Arm A, there were no significant differences in Grades 3 and 4 toxicities between the two regimens. The most frequently recorded Grade 3/4 toxicity was diarrhea in both treatment arms.
CONCLUSIONS
Irinotecan added to weekly bolus 5FU plus LV did not result in improvement in disease-free or overall survival in stage II or III colon cancer, but did increase toxicity.
TRIAL REGISTRATION
Australian New Zealand Clinical Trials Registry: ACTRN12610000148077.
背景
结肠癌是一个全球性的公共卫生问题。手术切除 III 期结肠癌后的辅助化疗已被证明可改善无病生存期和总生存期，目前被推荐为标准治疗。然而，对于 II 期疾病患者，其价值仍存在争议。在本研究设计时，氟尿嘧啶（5FU）加亚叶酸（LV）是结肠癌的标准辅助治疗。伊立替康（CPT-11）是一种拓扑异构酶 I 抑制剂，在转移性疾病中具有活性。在这项多中心辅助 III 期试验中，我们评估了在 II 期或 III 期结肠癌患者中添加伊立替康到每周 5FU 加 LV。
方法
该研究纳入了 873 名符合条件的患者。治疗包括每周静脉注射伊立替康 80mg/m2（A 组）或静脉注射 LV 200mg/m2 和 5FU 500mg/m2（B 组）。在 A 组中，连续四周每周给予治疗，然后休息两周，共六个周期，而在 B 组中，连续六周每周给予治疗，然后休息两周，共四个周期。主要终点是三年无病生存期（DFS）。
结果
A 组患者的总生存（OS）概率为 0.88，B 组为 0.86，而五年 OS 概率分别为 0.78 和 0.76（P=0.436）。此外，A 组和 B 组患者的三年 DFS 概率分别为 0.78 和 0.76（P=0.334）。除了白细胞减少和中性粒细胞减少，A 组患者发生率较高外，两种方案之间的 3 级和 4 级毒性无显著差异。最常记录的 3/4 级毒性是两组治疗中均出现的腹泻。
结论
伊立替康联合每周 5FU 加 LV 并未改善 II 期或 III 期结肠癌患者的无病生存期或总生存期，但增加了毒性。
试验注册
澳大利亚新西兰临床试验注册处：ACTRN12610000148077。
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