The variability of individual tolerance to methotrexate in cancer patients.
The variability of individual tolerance to methotrexate in cancer patients.
复制标题
DOI：
10.1038/bjc.1971.38
复制
发表时间：
1971-06
影响因子：
8.8
通讯作者：
McCall, C B
中科院分区：
文献类型：
--
作者：
Hansen, H H;Selawry, O S;Holland, J F;McCall, C B
研究了49例血清肌酐和/或血尿素氮正常的晚期癌症患者对单次或大间隔剂量甲氨蝶呤的个体耐受性。甲氨蝶呤静脉输注1小时，初始剂量为80-120 mg./m2体表面积。剂量每2周增加50%，直到出现中度毒性，任意定义为白细胞减少<5000/mm。3、血小板减少症<100,000/mm。3、口腔黏膜或肠道出现毒性。产生毒性初步证据所需的个体剂量在50至900毫克/平方米之间变化18倍。起始剂量超过80毫克/平方米就有潜在危险。剂量限制性毒性包括81%的患者伴或不伴口炎的白细胞减少，19%的患者伴白细胞减少的口炎。19%的患者有血小板减少症，但绝不是单独的剂量限制因素。白细胞减少总是先于血小板减少。白细胞和血小板的血液学毒性最低点分别在5-15天和9-14天之间变化很大，而口腔溃疡发生时，通常在给药后3-6天开始。其他毒性表现包括皮肤改变8例，肝功能障碍7例，结膜炎7例，恶心呕吐6例，脱发4例，腹泻3例。预测毒性的唯一因素是病人的年龄。药物耐受性与以前的化疗或放疗、体重减轻、血清白蛋白或预处理血清叶酸水平无关。
Individual tolerance to single or widely spaced doses of methotrexate was explored in 49 patients with advanced cancer with normal serum creatinine and/or blood urea nitrogen. Methotrexate was given as an intravenous infusion over 1 hour at initial doses of 80-120 mg./m2 body surface area. The doses were increased by 50% increments every 2 weeks until moderate toxicity occurred, arbitrarily defined as leukopenia <5000/mm.3, and/or thrombocytopenia <100,000/mm.3, and/or the appearance of oral mucous or intestinal toxicity. The individual dose required to produce initial evidence of toxicity varied by a factor of 18 between 50 and 900 mg./m2. Starting doses above 80 mg./m2 were potentially hazardous. Dose limiting toxicity consisted of leukopenia with or without stomatitis in 81% of the patients, and stomatitis without leukopenia, in 19%. Thrombocytopenia was seen in 19% of the patients, but was never a dose limiting factor alone. Leukopenia always preceded thrombocytopenia. The nadir for haematologic toxicity varied considerably between day 5-15 and 9-14 for leukocytes and platelets, respectively, while oral ulcerations, when they occurred, consistently began between days 3-6 after drug administration. Other toxic manifestations included dermatologic changes in 8 patients, hepatic dysfunction in 7, conjunctivitis in 7, nausea and vomiting in 6, alopecia in 4, and diarrhea in 3 patients. The only factor which predicted toxicity was the patient's age. Drug tolerance was independent of previous chemotherapy or radiotherapy, weight loss, serum albumin or pretreatment serum folic acid levels.