Earhart R H, Koeller J M, Davis H L
Cancer Treat Rep. 1982 May;66(5):1215-7.
6-Diazo-5-oxo-L-norleucine (DON), an L-glutamine antagonist, was administered to 25 evaluable patients with refractory advanced solid tumors in a phase I trial. A total of 58 evaluable courses of five daily iv injections every 3-4 weeks were given, at doses ranging from 7.5 to 90 mg/m2/day. The major dose-limiting toxicity was a syndrome of nausea, vomiting, malaise, and anorexia, which became severe at doses greater than 52.5 mg/m2/day. Diarrhea and stomatitis were less frequent. Hematologic toxicity included mild leukopenia with nadir on Day 6-8 and mild thrombocytopenia with nadir on Day 7-12. Transient decreases in serum calcium to 8.5--8.9 mg/dl were seen in seven of 12 patients receiving greater than or equal to 67.5 mg/m2/day. Dose reduction was required for all patients who received a course of DON at greater than 67.5 mg/m2/day, and a maximum tolerated total dose of 250 mg/m2 (50 mg/m2/day x 5) is suggested for this schedule. Mixed responses were seen in one patient with bladder carcinoma and in one with pulmonary adenocarcinoma.
6-重氮-5-氧代-L-正亮氨酸（DON）是一种L-谷氨酰胺拮抗剂，在一项I期试验中给予了25例可评估的难治性晚期实体瘤患者。每3 - 4周进行一次，共给予58个可评估疗程，每天静脉注射5次，剂量范围为7.5至90毫克/平方米/天。主要剂量限制性毒性是恶心、呕吐、不适和厌食综合征，在剂量大于52.5毫克/平方米/天时会变得严重。腹泻和口腔炎较少见。血液学毒性包括第6 - 8天出现最低点的轻度白细胞减少和第7 - 12天出现最低点的轻度血小板减少。在接受大于或等于67.5毫克/平方米/天的12例患者中，有7例出现血清钙短暂降至8.5 - 8.9毫克/分升。所有接受大于67.5毫克/平方米/天疗程DON的患者都需要减量，对于该方案，建议最大耐受总剂量为250毫克/平方米（50毫克/平方米/天×5）。在1例膀胱癌患者和1例肺腺癌患者中观察到混合反应。
