Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma - A randomized controlled trial
Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma - A randomized controlled trial
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DOI：
10.1001/jama.299.9.1019
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发表时间：
2008-03-05
影响因子：
120.7
通讯作者：
Rich, Tyvin A.
中科院分区：
文献类型：
--
作者：
Regine, William F.;Winter, Kathryn A.;Rich, Tyvin A.
背景 在局部晚期转移性胰腺癌患者中，与氟尿嘧啶相比，吉西他滨已被证明可以改善预后。 目的 确定在辅助氟尿嘧啶放化疗（化疗加放疗）中添加吉西他滨是否可以改善已切除胰腺腺癌患者的生存率。 设计、设置和参与者 随机对照 3 期试验 1998 年 7 月至 2002 年 7 月期间，在美国和加拿大的 164 家机构中，进行了完全肉眼完全切除的胰腺腺癌且既往未接受放疗或化疗，随访至 2006 年 8 月 18 日的患者。 干预化疗，采用氟尿嘧啶（每天持续输注 250 mg/m(2)；n= 230）或吉西他滨（30 分钟输注 1000 毫克） mg/m(2) 每周一次； n= 221) 放化疗前 3 周和放化疗后 12 周。所有患者均采用连续输注氟尿嘧啶（每天 250 mg/m(2)）进行放化疗（50.4 Gy）。 主要结果指标 所有患者的生存期和胰头肿瘤患者的生存期是主要终点。次要终点包括毒性。结果 共有 451 名患者被随机分组、符合条件且可分析。胰头肿瘤患者 (n= 388) 吉西他滨组的中位生存期为 20.5 个月，3 年生存率为 31%，而氟尿嘧啶组的中位生存期为 16.9 个月，3 年生存率为 22%（风险比，0.82 [95% 置信区间，0.65-1.03]；P=.09）。多变量分析显示治疗效果得到加强（风险比，0.80 [ 95% 置信区间，0.63-1.00]；P=.05）。 4级血液学毒性在氟尿嘧啶组为1%，在吉西他滨组为14%（P<85%）。结论在基于氟尿嘧啶的辅助放化疗中添加吉西他滨与切除胰腺癌患者的生存获益相关，尽管这种改善不具有统计学意义。试验注册临床试验。政府标识符：NCT00003216。
Context Among patients with locally advanced metastatic pancreatic adenocarcinoma, gemcitabine has been shown to improve outcomes compared with fluorouracil.Objective To determine if the addition of gemcitabine to adjuvant fluorouracil chemoradiation ( chemotherapy plus radiation) improves survival for patients with resected pancreatic adenocarcinoma.Design, Setting, and Participants Randomized controlled phase 3 trial of patients with complete gross total resection of pancreatic adenocarcinoma and no prior radiation or chemotherapy enrolled between July 1998 and July 2002 with follow- up through August 18, 2006, at 164 US and Canadian institutions.Intervention Chemotherapy with either fluorouracil ( continuous infusion of 250 mg/m(2) per day; n= 230) or gemcitabine ( 30- minute infusion of 1000 mg/m(2) once per week; n= 221) for 3 weeks prior to chemoradiation therapy and for 12 weeks after chemoradiation therapy. Chemoradiation with a continuous infusion of fluorouracil ( 250 mg/m(2) per day) was the same for all patients ( 50.4 Gy).Main Outcome Measures Survival for all patients and survival for patients with pancreatic head tumors were the primary end points. Secondary end points included toxicity.Results A total of 451 patients were randomized, eligible, and analyzable. Patients with pancreatic head tumors ( n= 388) had a median survival of 20.5 months and a 3- year survival of 31% in the gemcitabine group vs a median survival of 16.9 months and a 3- year survival of 22% in the fluorouracil group ( hazard ratio, 0.82 [ 95% confidence interval, 0.65- 1.03]; P=. 09). The treatment effect was strengthened on multivariate analysis ( hazard ratio, 0.80 [ 95% confidence interval, 0.63- 1.00]; P=. 05). Grade 4 hematologic toxicity was 1% in the fluorouracil group and 14% in the gemcitabine group ( P 85%).Conclusions The addition of gemcitabine to adjuvant fluorouracil- based chemoradiation was associated with a survival benefit for patients with resected pancreatic cancer, although this improvement was not statistically significant.Trial Registration clinicaltrials. gov Identifier: NCT00003216.