Bolli E, Saccomanno S, Mondini G, Aschele C, Guglielmi A, Ligas B, Connio M, Mori A, Rosso R, Sobrero A
Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Cancer Chemother Pharmacol. 1995;35(4):339-42. doi: 10.1007/BF00689455.
A total of 20 patients with advanced pancreatic adenocarcinoma were enrolled in a phase II trial testing the activity of 5-fluorouracil given at 370 mg/m2 as a rapid i.v. bolus for 5 consecutive days, preceded by a rapid i.v. bolus of 200 mg/m2 5-methyltetrahydrofolic acid. The treatment was repeated every 4 weeks. The median age of the patients was 68 years and their median Eastern Cooperative Oncology Group (ECOG) performance status was 1. There were 7 patients with locally advanced disease and 13 with distant metastases (median, 2 sites). A median of 3 monthly cycles of treatment (range, 1-7) were given, with a corresponding dose intensity of 396 mg/m2 per week (86% of that planned). No complete response, 1 partial response, and 8 cases of disease stabilization were obtained. In general the regimen was well tolerated, with only 2 patients suffering from grade 3 stomatitis or diarrhea; the most common toxicity was nausea, which was experienced by almost 50% of the patients. The combination of 5-methyltetrahydrofolate plus 5-fluorouracil appears as little effective in this disease as 5-fluorouracil plus 5-formyltetrahydrofolate (leucovorin). It is suggested that bolus 5-fluorouracil is so inactive as an "effector agent" against pancreatic cancer that its biochemical modulation with exogenous high-dose reduced folates cannot improve the therapeutic outcome produced by the fluoropyrimidine in these patients.
共有20例晚期胰腺腺癌患者参加了一项II期试验，该试验测试了以370mg/m²的剂量快速静脉推注5-氟尿嘧啶，连续5天给药，给药前先快速静脉推注200mg/m²的5-甲基四氢叶酸。每4周重复一次治疗。患者的中位年龄为68岁，其中位东部肿瘤协作组（ECOG）体能状态评分为1分。有7例局部晚期疾病患者和13例远处转移患者（中位转移部位为2个）。患者接受治疗的中位周期数为3个周期（范围1 - 7个周期），相应的剂量强度为每周396mg/m²（为计划剂量强度的86%）。未获得完全缓解，1例部分缓解，8例疾病稳定。总体而言，该方案耐受性良好，仅有2例患者出现3级口腔炎或腹泻；最常见的毒性反应是恶心，近50%的患者出现该症状。5-甲基四氢叶酸联合5-氟尿嘧啶在该疾病中的疗效似乎与5-氟尿嘧啶联合5-甲酰四氢叶酸（亚叶酸钙）一样差。提示静脉推注5-氟尿嘧啶作为一种抗胰腺癌的“效应剂”活性很低，以至于其与外源性高剂量还原型叶酸的生化调节不能改善这些患者中氟嘧啶产生的治疗效果。
