Williamson Stephen K, McCoy Sheryl A, Gandara David R, Dakhil Shaker R, Yost Kathleen J, Paradelo Jorge C, Atkins James N, Blanke Charles D, Abbruzzese James L
University of Kansas Medical Center, Kansas City, KS, USA.
Am J Clin Oncol. 2006 Apr;29(2):116-22. doi: 10.1097/01.coc.0000199883.10685.2b.
Metastatic esophageal carcinoma is an incurable disease with median survival duration of 6 to 8 months. Based on preclinical data suggesting a dose-dependent synergy between gemcitabine and irinotecan we have conducted a phase II trial in patients with advanced or metastatic esophageal carcinoma.
Patient eligibility included a diagnosis of squamous cell or adenocarcinoma of the esophagus/gastroesophageal (GE) junction, metastatic or recurrent disease, no CNS metastasis, no prior chemotherapy, prior adjuvant/neoadjuvant chemotherapy was allowed, no prior gemcitabine or irinotecan, performance status of 0 to 2 and adequate organ function. Patients received gemcitabine 1000 mg/m2 and irinotecan 100 mg/m2 given day 1 and day 8, every 3 weeks. The primary end point was the 6-month survival rate. The secondary end point was to assess qualitative and quantitative toxicities.
Fifty-seven eligible patients were accrued. There were 4 treatment-related deaths. The primary grade 3 to 4 toxic events were diarrhea, dehydration, neutropenia, thrombocytopenia, anemia, and anorexia; and 4 episodes of grade 3 to 5 febrile neutropenia, 1 fatal. The study was designed to detect a difference between the null hypothesis of 30% 6-month survival and the alternative hypothesis of 50% 6-month survival. The Kaplan-Meier estimate of 6-month survival is 56% (95% CI: 43-69%), with a median of 6.3 months. The median time to progression was 3.7 months. The 6-month progression-free survival estimate is 25% (95% CI: 13-36%).
The length of survival suggests that this combination has benefit similar to platinum containing regimens, however, the toxicity is substantial and is unlikely to prove superior to platinum containing regimens.
转移性食管癌是一种无法治愈的疾病，中位生存期为6至8个月。基于临床前数据表明吉西他滨和伊立替康之间存在剂量依赖性协同作用，我们对晚期或转移性食管癌患者进行了一项II期试验。
患者入选标准包括食管/胃食管（GE）交界处鳞状细胞癌或腺癌诊断、转移性或复发性疾病、无中枢神经系统转移、无既往化疗史（允许既往辅助/新辅助化疗）、无既往吉西他滨或伊立替康使用史、体能状态为0至2且器官功能良好。患者在第1天和第8天接受吉西他滨1000mg/m²和伊立替康100mg/m²，每3周一次。主要终点是6个月生存率。次要终点是评估定性和定量毒性。
共纳入57例符合条件的患者。有4例与治疗相关的死亡。主要的3至4级毒性事件为腹泻、脱水、中性粒细胞减少、血小板减少、贫血和厌食；以及4例3至5级发热性中性粒细胞减少，1例死亡。该研究旨在检测6个月生存率30%的零假设与6个月生存率50%的备择假设之间的差异。6个月生存率的Kaplan-Meier估计值为56%（95%CI：43-69%），中位生存期为6.3个月。中位进展时间为3.7个月。6个月无进展生存率估计值为25%（95%CI：13-36%）。
生存期表明这种联合方案具有与含铂方案相似的益处，然而，毒性较大，不太可能证明优于含铂方案。
