Van Cutsem E, Hoff P M, Harper P, Bukowski R M, Cunningham D, Dufour P, Graeven U, Lokich J, Madajewicz S, Maroun J A, Marshall J L, Mitchell E P, Perez-Manga G, Rougier P, Schmiegel W, Schoelmerich J, Sobrero A, Schilsky R L
University Hospital Gasthuisberg, Leuven, Belgium.
Br J Cancer. 2004 Mar 22;90(6):1190-7. doi: 10.1038/sj.bjc.6601676.
This study evaluates the efficacy of capecitabine using data from a large, well-characterised population of patients with metastatic colorectal cancer (mCRC) treated in two identically designed phase III studies. A total of 1207 patients with previously untreated mCRC were randomised to either oral capecitabine (1250 mg m(-2) twice daily, days 1-14 every 21 days; n=603) or intravenous (i.v.) bolus 5-fluorouracil/leucovorin (5-FU/LV; Mayo Clinic regimen; n=604). Capecitabine demonstrated a statistically significant superior response rate compared with 5-FU/LV (26 vs 17%; P<0.0002). Subgroup analysis demonstrated that capecitabine consistently resulted in superior response rates (P<0.05), even in patient subgroups with poor prognostic indicators. The median time to response and duration of response were similar and time to progression (TTP) was equivalent in the two arms (hazard ratio (HR) 0.997, 95% confidence interval (CI) 0.885-1.123, P=0.95; median 4.6 vs 4.7 months with capecitabine and 5-FU/LV, respectively). Multivariate Cox regression analysis identified younger age, liver metastases, multiple metastases and poor Karnofsky Performance Status as independent prognostic indicators for poor TTP. Overall survival was equivalent in the two arms (HR 0.95, 95% CI 0.84-1.06, P=0.48; median 12.9 vs 12.8 months, respectively). Capecitabine results in superior response rate, equivalent TTP and overall survival, an improved safety profile and improved convenience compared with i.v. 5-FU/LV as first-line treatment for MCRC. For patients in whom fluoropyrimidine monotherapy is indicated, capecitabine should be strongly considered. Following encouraging results from phase I and II trials, randomised trials are evaluating capecitabine in combination with irinotecan, oxaliplatin and radiotherapy. Capecitabine is a suitable replacement for i.v. 5-FU as the backbone of colorectal cancer therapy.
本研究利用两项设计相同的III期研究中大量特征明确的转移性结直肠癌（mCRC）患者的数据，评估了卡培他滨的疗效。共有1207例既往未接受过治疗的mCRC患者被随机分为口服卡培他滨组（1250 mg/m²，每日2次，第1 - 14天，每21天为一周期；n = 603）或静脉推注5-氟尿嘧啶/亚叶酸钙（5-FU/LV；梅奥诊所方案；n = 604）。与5-FU/LV相比，卡培他滨显示出具有统计学意义的更高缓解率（26%对17%；P < 0.0002）。亚组分析表明，即使在预后指标较差的患者亚组中，卡培他滨也始终能带来更高的缓解率（P < 0.05）。两组的中位缓解时间和缓解持续时间相似，疾病进展时间（TTP）相当（风险比（HR）0.997，95%置信区间（CI）0.885 - 1.123，P = 0.95；卡培他滨组和5-FU/LV组的中位TTP分别为4.6个月和4.7个月）。多因素Cox回归分析确定年龄较小、肝转移、多发转移以及卡氏功能状态较差是TTP不良的独立预后指标。两组的总生存期相当（HR 0.95，95% CI 0.84 - 1.06，P = 0.48；中位总生存期分别为12.9个月和12.8个月）。作为mCRC的一线治疗，与静脉注射5-FU/LV相比，卡培他滨缓解率更高、TTP和总生存期相当、安全性更好且便利性更佳。对于适合氟嘧啶单药治疗的患者，应强烈考虑使用卡培他滨。在I期和II期试验取得令人鼓舞的结果后，随机试验正在评估卡培他滨与伊立替康、奥沙利铂及放疗联合应用的情况。卡培他滨是静脉注射5-FU作为结直肠癌治疗基础用药的合适替代药物。
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