Adjuvant Chemotherapy With Gemcitabine and Long-term Outcomes Among Patients With Resected Pancreatic Cancer The CONKO-001 Randomized Trial
Adjuvant Chemotherapy With Gemcitabine and Long-term Outcomes Among Patients With Resected Pancreatic Cancer The CONKO-001 Randomized Trial
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DOI：
10.1001/jama.2013.279201
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发表时间：
2013-10-09
影响因子：
120.7
通讯作者：
Riess, Hanno
中科院分区：
文献类型：
--
作者：
Oettle, Helmut;Neuhaus, Peter;Riess, Hanno
胰腺癌患者的预后很差，即使在根治性切除后。以吉西他滨为基础的化疗是晚期胰腺癌的标准治疗方法，但其对辅助治疗中生存率的影响尚未得到证实。目的分析既往报道的吉西他滨辅助治疗改善无病生存率是否转化为改善总生存率。设计、设置和患者CONKO-001（Charite Onkologie 001），一项多中心、开放标签、III期随机试验，旨在评价吉西他滨在胰腺癌患者肿瘤完全切除术后的疗效和毒性。在1998年7月至2004年12月期间，在德国和奥地利的88家医院中，肉眼完全切除胰腺癌的患者进入研究。随访于2012年9月结束。干预在根据肿瘤分期、淋巴结状态和切除状态分层后，患者被随机分配到辅助吉西他滨治疗组（1g/m2，第1、8、15天，每4周1次）或单独观察组。次要终点包括治疗安全性和总生存期，总生存期定义为从随机化日期到死亡的时间。失访的患者在其最后一次随访的日期进行审查。结果共有368例患者被随机分组，354例符合意向治疗分析。截至2012年9月，308例患者（87.0% [95% CI，83.1%-90.1%]）复发，316例患者（89.3% [95% CI，85.6%-92.1%]）死亡。中位随访时间为136个月。治疗组中位无病生存期为13.4（95%CI，11.6-15.3）个月，观察组为6.7（95%CI，6.0-7.5）个月（风险比，0.55 [95%CI，0.44-0.69]; P
IMPORTANCE The prognosis for patients with pancreatic cancer is poor, even after resection with curative intent. Gemcitabine-based chemotherapy is standard treatment for advanced pancreatic cancer, but its effect on survival in the adjuvant setting has not been demonstrated.OBJECTIVE To analyze whether previously reported improvement in disease-free survival with adjuvant gemcitabine therapy translates into improved overall survival.DESIGN, SETTING, AND PATIENTS CONKO-001 (Charite Onkologie 001), a multicenter, open-label, phase 3 randomized trial to evaluate the efficacy and toxicity of gemcitabine in patients with pancreatic cancer after complete tumor resection. Patients with macroscopically completely removed pancreatic cancer entered the study between July 1998 and December 2004 in 88 hospitals in Germany and Austria. Follow-up ended in September 2012.INTERVENTIONS After stratification for tumor stage, nodal status, and resection status, patients were randomly assigned to either adjuvant gemcitabine treatment (1g/m(2) d 1, 8, 15, q 4 weeks) for 6 months or to observation alone.MAIN OUTCOMES AND MEASURES The primary end point was disease-free survival. Secondary end points included treatment safety and overall survival, with overall survival defined as the time from date of randomization to death. Patients lost to follow-up were censored on the date of their last follow-up.RESULTS A total of 368 patients were randomized, and 354 were eligible for intention-to-treat-analysis. By September 2012, 308 patients (87.0% [95% CI, 83.1%-90.1%]) had relapsed and 316 patients (89.3% [95% CI, 85.6%-92.1%]) had died. The median follow-up time was 136 months. The median disease-free survival was 13.4 (95% CI, 11.6-15.3) months in the treatment group compared with 6.7 (95% CI, 6.0-7.5) months in the observation group (hazard ratio, 0.55 [95% CI, 0.44-0.69]; P