Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
JAMA. 2013 Oct 9;310(14):1473-81. doi: 10.1001/jama.2013.279201.
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.
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 (Charité 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.
After stratification for tumor stage, nodal status, and resection status, patients were randomly assigned to either adjuvant gemcitabine treatment (1g/m2 d 1, 8, 15, q 4 weeks) for 6 months or to observation alone.
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.
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 < .001). Patients randomized to adjuvant gemcitabine treatment had prolonged overall survival compared with those randomized to observation alone (hazard ratio, 0.76 [95% CI, 0.61-0.95]; P = .01), with 5-year overall survival of 20.7% (95% CI, 14.7%-26.6%) vs 10.4% (95% CI, 5.9%-15.0%), respectively, and 10-year overall survival of 12.2% (95% CI, 7.3%-17.2%) vs 7.7% (95% CI, 3.6%-11.8%).
Among patients with macroscopic complete removal of pancreatic cancer, the use of adjuvant gemcitabine for 6 months compared with observation alone resulted in increased overall survival as well as disease-free survival. These findings provide strong support for the use of gemcitabine in this setting.
isrctn.org Identifier: ISRCTN34802808.
即使进行了以治愈为目的的切除，胰腺癌患者的预后仍然很差。吉西他滨为基础的化疗是晚期胰腺癌的标准治疗方法，但在辅助治疗环境下其对生存的影响尚未得到证实。
分析先前报道的吉西他滨辅助治疗在无病生存期方面的改善是否转化为总生存期的改善。
设计、设置和患者：CONKO-001（Charité Onkologie 001），一项多中心、开放性、三期随机临床试验，旨在评估吉西他滨在完全切除肿瘤的胰腺癌患者中的疗效和毒性。1998 年 7 月至 2004 年 12 月，德国和奥地利的 88 家医院共招募了宏观完全切除的胰腺癌患者入组该研究。随访于 2012 年 9 月结束。
在肿瘤分期、淋巴结状态和切除状态分层后，患者被随机分配至辅助吉西他滨治疗组（1g/m2，第 1、8、15 天，q4 周）6 个月或观察组。
主要终点为无病生存期。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分组日期到死亡的时间。失访患者的随访截止日期为最后一次随访日期。
共随机分配 368 例患者，354 例符合意向治疗分析。截至 2012 年 9 月，308 例（87.0% [95%CI，83.1%-90.1%]）患者复发，316 例（89.3% [95%CI，85.6%-92.1%]）患者死亡。中位随访时间为 136 个月。治疗组无病生存期中位数为 13.4 个月（95%CI，11.6-15.3），观察组为 6.7 个月（95%CI，6.0-7.5）（风险比，0.55 [95%CI，0.44-0.69]；P < 0.001）。与观察组相比，接受辅助吉西他滨治疗的患者总生存期延长（风险比，0.76 [95%CI，0.61-0.95]；P = 0.01），分别为 5 年总生存率 20.7%（95%CI，14.7%-26.6%）和 10.4%（95%CI，5.9%-15.0%），10 年总生存率为 12.2%（95%CI，7.3%-17.2%）和 7.7%（95%CI，3.6%-11.8%）。
在宏观完全切除胰腺癌患者中，与观察组相比，使用吉西他滨辅助治疗 6 个月可提高总生存期和无病生存期。这些发现为吉西他滨在这一领域的应用提供了有力支持。
isrctn.org 标识符：ISRCTN34802808。
