Altman S J, Fletcher W S, Andrews N C, Wilson W L, Pischer T
Cancer. 1975 Apr;35(4):1145-7. doi: 10.1002/1097-0142(197504)35:4<1145::aid-cncr2820350419>3.0.co;2-p.
Yoshi 864 was given i.v. push daily times 5 with 6 weeks' followup. Dose escalation was from 0.25 mg/kg to 2.7 mg/kg. Toxicity and effectiveness were first seen at 1.5 mg/kg. Twenty-five courses were given to 16 patients at or above this level. In 16 of 22 courses, exclusive of CML, thrombopenia and/or leukopenia occurred. Mean platelet and WBC nadirs occurred on day 24 and 29 with recovery taking 1-2 weeks and 2-3 weeks respectively. Hb fell in 11 courses. At 2.7 mg/kg, nausea and vomiting lasting 6-12 days occurred in 3 of 7 courses; during 5 coures patients slept 20 hours a day, and 1 was comatose for 2 days. Two patients with squamous cell carcinoma and 1 with an unknown primary responded. Both patients with CML had clinical remissions. It is recommended that a cooperative Phase II Study in a broad spectrum of human solid tumors including lymphomas and chronic myelocytic leukemia be undertaken at a dose level of 2 mg/kg.
给Yoshi 864每日静脉推注，共5次，随访6周。剂量从0.25毫克/千克逐步增加至2.7毫克/千克。在1.5毫克/千克时首次观察到毒性和疗效。16名患者在该剂量水平及以上接受了25个疗程的治疗。在22个疗程中的16个（不包括慢性粒细胞白血病），出现了血小板减少和/或白细胞减少。平均血小板最低点和白细胞最低点分别出现在第24天和第29天，恢复分别需要1 - 2周和2 - 3周。11个疗程中血红蛋白下降。在2.7毫克/千克时，7个疗程中的3个出现了持续6 - 12天的恶心和呕吐；5个疗程中患者每天睡20小时，1名患者昏迷2天。2例鳞状细胞癌患者和1例原发灶不明的患者有反应。2例慢性粒细胞白血病患者均有临床缓解。建议在2毫克/千克的剂量水平上，对包括淋巴瘤和慢性粒细胞白血病在内的广泛人类实体瘤进行合作的II期研究。
