Asmis T, Berry S, Cosby R, Chan K, Coburn N, Rother M
The Ottawa Hospital Cancer Centre, Ottawa, ON.
Sunnybrook Odette Cancer Centre, Toronto, ON.
Curr Oncol. 2014 Dec;21(6):318-28. doi: 10.3747/co.21.2146.
Before the emergence of first-line combination chemotherapy, the standard of care for unresectable metastatic colorectal cancer (mcrc) was first-line monotherapy with modulated 5-fluorouracil. Several large phase iii randomized controlled trials, now completed, have assessed whether a planned sequential chemotherapy strategy-beginning with fluoropyrimidine monotherapy until treatment failure, followed by another regimen (either monotherapy or combination chemotherapy) until treatment failure-could result in the same survival benefit produced with an upfront combination chemotherapy strategy, but with less toxicity for patients.
The medline and embase databases, and abstracts from meetings of the American Society for Clinical Oncology and the European Society for Medical Oncology, were searched for reports comparing a sequential strategy of chemotherapy with an upfront combination chemotherapy in adult patients with mcrc. Publications that reported efficacy or toxicity data (or both) were included.
The five eligible trials that were identified included 4532 patients. A meta-analysis of those trials demonstrates a statistically significant survival advantage for combination chemotherapy (hazard ratio: 0.92; 95% confidence interval: 0.86 to 0.99). However, the median survival advantage (3-6 weeks in most trials) is small and of questionable clinical significance. Three trials reported first-line toxicities. Upfront combination chemotherapy results in significantly more neutropenia, febrile neutropenia, thrombocytopenia, diarrhea, nausea, vomiting, and sensory neuropathy. Sequential chemotherapy results in significantly more hand-foot syndrome.
Given the small survival advantage associated with upfront combination chemotherapy, planned sequential chemotherapy and upfront combination chemotherapy can both be considered treatment strategies. Treatment should be chosen on an individual basis considering patient and tumour characteristics, toxicity of each strategy, and patient preference.
在一线联合化疗出现之前，不可切除转移性结直肠癌（mCRC）的标准治疗方案是采用改良的5-氟尿嘧啶进行一线单药治疗。目前已完成的几项大型III期随机对照试验评估了一种计划性序贯化疗策略——先采用氟嘧啶单药治疗直至治疗失败，然后采用另一种方案（单药治疗或联合化疗）直至治疗失败——是否能产生与 upfront 联合化疗策略相同的生存获益，但对患者的毒性更小。
检索了Medline和Embase数据库以及美国临床肿瘤学会和欧洲医学肿瘤学会会议的摘要，以查找比较mCRC成年患者序贯化疗策略与 upfront 联合化疗的报告。纳入了报告疗效或毒性数据（或两者）的出版物。
确定的五项符合条件的试验共纳入4532例患者。对这些试验的荟萃分析表明，联合化疗具有统计学显著的生存优势（风险比：0.92；95%置信区间：0.86至0.99）。然而，中位生存优势（大多数试验中为3 - 6周）较小且临床意义存疑。三项试验报告了一线毒性。upfront联合化疗导致更多的中性粒细胞减少、发热性中性粒细胞减少、血小板减少、腹泻、恶心、呕吐和感觉神经病变。序贯化疗导致更多的手足综合征。
鉴于 upfront 联合化疗的生存优势较小，计划性序贯化疗和 upfront 联合化疗均可被视为治疗策略。应根据患者个体情况，考虑患者和肿瘤特征、每种策略的毒性以及患者偏好来选择治疗方案。
