Seymour Matthew T, Maughan Timothy S, Ledermann Jonathan A, Topham Clare, James Roger, Gwyther Stephen J, Smith David B, Shepherd Stephen, Maraveyas Anthony, Ferry David R, Meade Angela M, Thompson Lindsay, Griffiths Gareth O, Parmar Mahesh Kb, Stephens Richard J
Cookridge Hospital, Leeds, UK.
Velindre Hospital, Cardiff, UK.
Lancet. 2007 Jul 14;370(9582):143-152. doi: 10.1016/S0140-6736(07)61087-3.
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.
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 C, 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.
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).
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.
在无法治愈的情况下，如果患者想要在不良反应最小的情况下获得最长的疾病控制期，那么单独或联合使用抗癌药物的顺序可能很重要。我们比较了序贯化疗和联合化疗策略在未经治疗的晚期或转移性结直肠癌患者中的效果，这些患者无论治疗反应如何都被视为无法治愈。
我们研究了晚期结直肠癌患者，开始进行非治愈性治疗。2135名未经治疗的患者被随机分配到三种治疗策略中，比例为1:1:1。策略A（对照组）是单药氟尿嘧啶（每2周静脉滴注48小时，并同时给予亚叶酸钙），直至病情进展，然后使用单药伊立替康。策略B是先使用氟尿嘧啶，直至病情进展，然后进行联合化疗。策略C是从一开始就进行联合化疗。在策略B和C中，患者被随机分配接受以下联合方案：氟尿嘧啶加伊立替康（B-ir组和C-ir组）或氟尿嘧啶加奥沙利铂（B-ox组和C-ox组）。主要终点是总生存期，采用意向性分析。本研究已注册为国际标准随机对照试验，编号为ISRCTN 79877428。
分配到对照策略A的患者的中位生存期为13.9个月。其他各组的中位生存期更长（B-ir组为15.0个月，B-ox组为15.2个月，C-ir组为16.7个月，C-ox组为15.4个月）。然而，将每组与对照组进行对数秩检验比较发现，只有C-ir组（包括伊立替康的一线联合策略）满足优越性统计检验（p=0.01）。策略B与策略C的总体比较在预先设定的非劣效性边界HR=1.18或更低范围内（HR=1.06，90%CI 0.97-1.17）。
我们的数据挑战了这样一种假设，即在这种无法治愈的情况下，必须首先使用最大耐受治疗。初始单药治疗并在需要时升级为联合治疗的分阶段方法并不比一线联合治疗差，是与患者讨论的另一种选择。
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