Kane R C, Cashdollar M R, Bernath A M
Cancer Treat Rep. 1978 Oct;62(10):1521-5.
Thirty-six patients with advanced colorectal carcinoma who had not received prior chemotherapy and had tumor sites measurable or evaluable for response received methyl-CCNU at a dose of 175 mg/m2 orally on Day 1 plus 5-fluorouracil at a dose of 30 mg/kg/24 hours by continuous iv infusion for 120 hours (Days 1-5). Doses were chosen to approach the maximum which could be administered in combination. The cycle was repeated 6 weeks later. Objective partial responses occurred in six patients (17%), with five responses apparent after the first cycle and one additional response after the second cycle. The response duration ranged from 1.5 to 18+ months (median, 5 months). Dose-limiting toxic effects included mucositis in 18 patients (50%) and dermatitis in nine patients (25%), while leukopenia (less than 4000 cells/mm3) and thrombocytopenia (less than 100,000 platelets/mm3) were observed on at least one occasion during therapy in 52% and 46% of patients, respectively. 5-Fluorouracil administration by infusion avoided overlapping myelosuppression and allowed a higher total dose to be given with methyl-CCNU. However, the response to the combination did not exceed the results anticipated for the use of either drug alone.
36例未接受过前期化疗且肿瘤部位可测量或可评估反应的晚期结直肠癌患者，于第1天口服甲基环己亚硝脲，剂量为175mg/m²，同时持续静脉输注5-氟尿嘧啶，剂量为30mg/kg/24小时，持续120小时（第1 - 5天）。选择这些剂量以接近联合用药时可给予的最大剂量。6周后重复该周期。6例患者（17%）出现客观部分缓解，5例在第一个周期后出现缓解，1例在第二个周期后出现额外缓解。缓解持续时间为1.5至18 +个月（中位值为5个月）。剂量限制性毒性反应包括18例患者（50%）出现黏膜炎，9例患者（25%）出现皮炎，而分别有52%和46%的患者在治疗期间至少有一次观察到白细胞减少（低于4000个细胞/mm³）和血小板减少（低于100,000个血小板/mm³）。通过输注给予5-氟尿嘧啶避免了骨髓抑制的重叠，并允许与甲基环己亚硝脲联合给予更高的总剂量。然而，联合用药的反应并未超过单独使用任何一种药物预期的结果。
