Christie Hospital, Manchester, United Kingdom.
N Engl J Med. 2010 Apr 8;362(14):1273-81. doi: 10.1056/NEJMoa0908721.
There is no established standard chemotherapy for patients with locally advanced or metastatic biliary tract cancer. We initially conducted a randomized, phase 2 study involving 86 patients to compare cisplatin plus gemcitabine with gemcitabine alone. After we found an improvement in progression-free survival, the trial was extended to the phase 3 trial reported here.
We randomly assigned 410 patients with locally advanced or metastatic cholangiocarcinoma, gallbladder cancer, or ampullary cancer to receive either cisplatin (25 mg per square meter of body-surface area) followed by gemcitabine (1000 mg per square meter on days 1 and 8, every 3 weeks for eight cycles) or gemcitabine alone (1000 mg per square meter on days 1, 8, and 15, every 4 weeks for six cycles) for up to 24 weeks. The primary end point was overall survival.
After a median follow-up of 8.2 months and 327 deaths, the median overall survival was 11.7 months among the 204 patients in the cisplatin-gemcitabine group and 8.1 months among the 206 patients in the gemcitabine group (hazard ratio, 0.64; 95% confidence interval, 0.52 to 0.80; P<0.001). The median progression-free survival was 8.0 months in the cisplatin-gemcitabine group and 5.0 months in the gemcitabine-only group (P<0.001). In addition, the rate of tumor control among patients in the cisplatin-gemcitabine group was significantly increased (81.4% vs. 71.8%, P=0.049). Adverse events were similar in the two groups, with the exception of more neutropenia in the cisplatin-gemcitabine group; the number of neutropenia-associated infections was similar in the two groups.
As compared with gemcitabine alone, cisplatin plus gemcitabine was associated with a significant survival advantage without the addition of substantial toxicity. Cisplatin plus gemcitabine is an appropriate option for the treatment of patients with advanced biliary cancer. (ClinicalTrials.gov number, NCT00262769.)
局部晚期或转移性胆道癌患者尚无既定的标准化疗方案。我们最初对 86 例患者进行了一项随机、2 期研究，比较顺铂联合吉西他滨与吉西他滨单药治疗的效果。在观察到无进展生存期改善后，我们将该试验扩展至本文报告的 3 期试验。
我们将 410 例局部晚期或转移性胆管癌、胆囊癌或壶腹癌患者随机分为两组，分别接受顺铂（25mg/平方米体表面积）联合吉西他滨（1000mg/平方米，第 1 和第 8 天用药，每 3 周为一个周期，共 8 个周期）或吉西他滨单药治疗（1000mg/平方米，第 1、8 和 15 天用药，每 4 周为一个周期，共 6 个周期），最长用药 24 周。主要终点为总生存期。
中位随访 8.2 个月后，204 例接受顺铂-吉西他滨治疗的患者中有 327 例死亡，中位总生存期为 11.7 个月；206 例接受吉西他滨单药治疗的患者中有 327 例死亡，中位总生存期为 8.1 个月（风险比，0.64；95%置信区间，0.52 至 0.80；P<0.001）。顺铂-吉西他滨组中位无进展生存期为 8.0 个月，吉西他滨单药组为 5.0 个月（P<0.001）。此外，顺铂-吉西他滨组的肿瘤控制率显著提高（81.4%比 71.8%，P=0.049）。两组的不良反应相似，除顺铂-吉西他滨组中性粒细胞减少症发生率较高外（P=0.049），两组中性粒细胞减少症相关感染发生率相似。
与吉西他滨单药治疗相比，顺铂联合吉西他滨治疗可显著提高生存获益，且未增加明显毒性。顺铂联合吉西他滨是治疗晚期胆道癌的一种合理选择。（临床试验.gov 注册号，NCT00262769）。
