Franklin R, Samson M K, Fraile R J, Abu-Zahra H, O'Bryan R, Baker L H
Cancer. 1980 Sep 1;46(5):1104-8. doi: 10.1002/1097-0142(19800901)46:5<1104::aid-cncr2820460505>3.0.co;2-t.
Maytansine, a new ansa macrolide antitumor antibiotic, was administered to a total of 107 patients in a Phase I-II study. Dose-limiting toxic reactions which occurred at 0.75-1.0 mg/M2 in both Phase I and II were neurologic and consisted primarily of lethargy/weakness (a debilitation syndrome) and paresthesias. Gastrointestinal and neurologic toxic reactions increased in frequency and severity as a function of dose. Myelosuppression, while infrequent, occurred only in previously treated patients. Changes in liver function tests were subclinical. Two partial remissions were observed at a dose-level of 0.5 mg/M2 in Phase I:1 patient with squamous cell carcinoma of the lung responded for five weeks, while the other patient with adenocarcinoma of the lung responded for four weeks. One partial remission, lasting 14 weeks was seen in Phase II in a patient with malignant melanoma treated at dose-level of 1.0 mg/M2. All responses were in heavily pretreated patients. pairs of small bowel biopsy specimen used to define the mitotic index demonstrated peak mitotic arrest at 24 hours in contrast to vinca alkaloids which appear to have a peak mitotic arrest at 12-24 hours.
美登素是一种新型的安莎大环内酯类抗肿瘤抗生素，在一项I-II期研究中对总共107例患者进行了给药。在I期和II期，剂量限制毒性反应发生在0.75-1.0mg/M²，表现为神经毒性，主要包括嗜睡/虚弱（一种衰弱综合征）和感觉异常。胃肠道和神经毒性反应的频率和严重程度随剂量增加而增加。骨髓抑制虽不常见，但仅发生在既往接受过治疗的患者中。肝功能检查的变化为亚临床改变。在I期，0.5mg/M²剂量水平观察到2例部分缓解：1例肺鳞状细胞癌患者缓解了5周，另1例肺腺癌患者缓解了4周。在II期，用1.0mg/M²剂量治疗的1例恶性黑色素瘤患者出现了1次持续14周的部分缓解。所有缓解均出现在预处理程度较高的患者中。用于确定有丝分裂指数的成对小肠活检标本显示，与长春花生物碱在12-24小时出现有丝分裂高峰阻滞不同，美登素在24小时出现有丝分裂高峰阻滞。
