Department of Medical Oncology, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, CH, Switzerland.
Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Hirschengraben 84, 8001, Zurich, CH, Switzerland.
BMC Cancer. 2018 Jan 11;18(1):72. doi: 10.1186/s12885-017-3967-0.
Biliary tract cancer (BTC) is a dismal disease, even after curative intent surgery. We conducted this prospective, non-randomized phase II study to evaluate the feasibility and efficacy of cisplatin and gemcitabine as adjuvant treatment in patients with resected BTC.
Patients initially received gemcitabine 1000 mg/m alone on days 1, 8 and 15 every 28-days for a total of six cycles (single agent cohort), and after protocol amendment a combination therapy with gemcitabine 1000 mg/m and cisplatin 25 mg/m on days 1 and 8 was administered every 21 days for a total of eight cycles (combined regimen cohort). Treatment was planned to start within eight weeks after curative intent resection. Adverse events, disease-free survival and overall survival were assessed.
Overall 30 patients were enrolled in the study from August 2008 and last patient was enrolled at 2nd December 2014. The follow-up of the patients ended at 31st December 2016. The first 9 patients received single-agent gemcitabine. The interim analysis met the predefined feasibility criteria and, from September 2010 on, the second group of 21 patients received the combination of cisplatin plus gemcitabine. In the single-agent cohort with gemcitabine the median relative dose intensity (RDI) was 100% (IQR 88.3-100). Patients treated with the combination cisplatin-gemcitabine received an overall median RDI of 100% (IQR 50-100) for cisplatin and 100% (IQR 75-100) for gemcitabine respectively. The most significant non-hematological adverse events (grade 3 or 4) were fatigue (20%), infections during neutropenia (10%), and two cases of biliary sepsis (7%). Abnormal liver function was seen in 10% of the patients. One patient died due to infectious complications during treatment with cisplatin and gemcitabine. The median disease-free survival (DFS) was 14.9 months (95% CI 0-33.8) with a corresponding 3-year DFS of 43.1 ± 9.1%. The median overall survival (OS) was 40.6 months (95% CI 18.8-62.3) with a 3-year OS of 55.7 ± 9.2%. No statistically significant differences in survival were seen between the two treatment cohorts.
Adjuvant chemotherapy with gemcitabine with or without cisplatin was well tolerated and resulted in promising survival of the patients.
The study was retrospectively registered on 25th June 2009 at clinicaltrials.gov ( NCT01073839 ).
胆管癌（BTC）即使在根治性手术后也是一种预后极差的疾病。我们进行了这项前瞻性、非随机的 II 期研究，以评估顺铂和吉西他滨作为 BTC 患者辅助治疗的可行性和疗效。
患者最初接受吉西他滨 1000mg/m2，第 1、8 和 15 天，每 28 天为一个周期，共 6 个周期（单药组），然后根据方案修订，吉西他滨 1000mg/m2 和顺铂 25mg/m2 联合治疗，第 1 和 8 天每 21 天一个周期，共 8 个周期（联合治疗组）。治疗计划在根治性手术后 8 周内开始。评估不良反应、无病生存期和总生存期。
2008 年 8 月至 2014 年 12 月 2 日期间共纳入 30 例患者，最后一名患者于 2016 年 12 月 31 日随访结束。患者的随访于 2016 年 12 月 31 日结束。前 9 例患者接受单药吉西他滨治疗。中期分析符合预定的可行性标准，从 2010 年 9 月开始，第二组 21 例患者接受顺铂加吉西他滨联合治疗。在吉西他滨单药组中，中位相对剂量强度（RDI）为 100%（IQR 88.3-100）。接受顺铂-吉西他滨联合治疗的患者顺铂总体中位 RDI 为 100%（IQR 50-100），吉西他滨中位 RDI 为 100%（IQR 75-100）。最显著的非血液学不良事件（3 级或 4 级）为疲劳（20%）、中性粒细胞减少期间感染（10%）和 2 例胆道败血症（7%）。10%的患者出现肝功能异常。1 例患者因顺铂和吉西他滨治疗期间感染并发症而死亡。无病生存期（DFS）中位数为 14.9 个月（95%CI 0-33.8），相应的 3 年 DFS 为 43.1±9.1%。总生存期（OS）中位数为 40.6 个月（95%CI 18.8-62.3），3 年 OS 为 55.7±9.2%。两组治疗的生存无统计学差异。
吉西他滨联合或不联合顺铂辅助化疗耐受性良好，患者生存获益显著。
该研究于 2009 年 6 月 25 日在 clinicaltrials.gov 进行了回顾性注册（NCT01073839）。
