Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial
Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial
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DOI：
10.1016/s0140-6736(07)61087-3
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发表时间：
2007-07-14
期刊：
影响因子：
168.9
通讯作者：
Stephens, Richard J.
中科院分区：
文献类型：
--
作者：
Seymour, Matthew T.;Maughan, Timothy S.;Stephens, Richard J.
背景在非治愈性环境中，如果患者要获得最长的疾病控制期和最小的不良反应，抗癌药物的使用顺序（单独或联合）可能很重要。我们比较了序贯和联合化疗策略在未经预处理的晚期或转移性结直肠癌患者，谁被认为是不可能治愈的responsibility.Methods，我们研究了晚期结直肠癌患者，开始治疗与非治愈的意图。2135名未经治疗的患者按1：1：1的比例随机分配至三种治疗策略。策略A（对照组）为单药氟尿嘧啶（每2周给予左亚叶酸48小时以上）直至失败，然后单药伊立替康。策略B为氟尿嘧啶治疗失败后联合化疗。策略C从一开始就是联合化疗。在策略B和Q中，患者被随机分配接受氟尿嘧啶+伊立替康（组B-ir和C-ir）或氟尿嘧啶+奥沙利铂（组B-ox和C-ox）作为联合方案。主要终点是总生存期，按意向治疗分析。本研究已注册为国际标准随机对照试验，编号ISRCTN 79877428。结果分配到控制策略A的患者中位生存期为13.9个月。其他各组的中位生存期更长（B-ir 15.0、B-ox 15.2、C-ir 16.7和C-ox 15.4个月）。然而，各组与对照组的对数秩比较显示，仅C-ir（包括伊立替康的一线联合策略）满足优效性的统计学检验（p=0.01）。策略B与策略C的总体比较在预定的HR=1.18或更低的非劣效性边界内（HR=1.06，90%CI 0.97-1.17）。解释我们的数据挑战了这样的假设，即在这种非治愈性环境中，最大耐受治疗必须用于一线。初始单药治疗在需要时升级为联合治疗的阶段性方法不劣于一线联合治疗，是与患者讨论的替代选择。
Background In the non-curative setting, the sequence in which anticancer agents are used, singly or in combination, may be important if patients are to receive the maximum period of disease control with the minimum of adverse effects. We compared sequential and combination chemotherapy strategies in patients with unpretreated advanced or metastatic colorectal cancer, who were regarded as not potentially curable irrespective of response.Methods We studied patients with advanced colorectal cancer, starting treatment with non-curative intent. 2135 unpretreated patients were randomly assigned to three treatment strategies in the ratio 1:1:1. Strategy A (control group) was single-agent fluorouracil (given with levofolinate over 48 h every 2 weeks) until failure, then single-agent irinotecan. Strategy B was fluorouracil until failure, then combination chemotherapy. Strategy C was combination chemotherapy from the outset. Within strategies B and Q patients were randomly assigned to receive, as the combination regimen, fluorouracil plus irinotecan (groups B-ir and C-ir) or fluorouracil plus oxaliplatin (groups B-ox and C-ox). The primary endpoint was overall survival, analysed by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 79877428.Results Median survival of patients allocated to control strategy A was 13.9 months. Median survival of each of the other groups was longer (B-ir 15.0, B-ox 15.2, C-ir 16.7, and C-ox 15.4 months). However, log-rank comparison of each group against control showed that only C-ir - the first-line combination strategy including irinotecan-satisfied the statistical test for superiority (p=0.01). Overall comparison of strategy B with strategy C was within the predetermined non-inferiority boundary of HR=1.18 or less (HR=1.06, 90% CI 0.97-1.17).Interpretation Our data challenge the assumption that, in this non-curative setting, maximum tolerable treatment must necessarily be used first-line. The staged approach of initial single-agent treatment upgraded to combination when required is not worse than first-line combination, and is an alternative option for discussion with patients.