Goldsmith M A, Bhardwaj S, Ohnuma T, Greenspan E M, Holland J F
Cancer Clin Trials. 1980 Fall;3(3):197-202.
m-AMSA is a synthetic aminoacridine DNA intercalator found to have experimental murine antitumor activity. A phase I investigation was undertaken in 71 patients with solid tumors and acute leukemia. Using an intermittent every 3-week schedule in solid tumors, toxicity encountered was primarily hematologic, predominantly leukopenia with relative platelet sparing. The recommended dose for phase II evaluation in patients with solid tumors is 90 mg/m2 every 3 weeks; patients with minimal prior therapy could be treated at 120 mg/m2 and patients with hepatic dysfunction or marginal bone marrow reserve should have an initial dose reduction to 70 mg/m2. Therapeutic activity was seen in Hodgkin's disease, hepatoma, and epidermoid carcinoma of the esophagus. Various dose schedules were studied in leukemia. The recommended dose for phase II evaluation is 120 mg/m2 daily for 5 days as a daily 30-minute infusion. At this dose, nausea, vomiting, mucositis, alopecia, and hepatic toxicity were noted. Therapeutic activity was seen in AML, blastic CML, and CLL. Further clinical trials with this agent are warranted.
m-AMSA是一种合成氨基吖啶DNA嵌入剂，已发现其具有实验性小鼠抗肿瘤活性。对71例实体瘤和急性白血病患者进行了I期研究。在实体瘤中采用每3周一次的间歇给药方案，所遇到的毒性主要是血液学毒性，主要为白细胞减少，相对血小板受影响较小。实体瘤患者II期评估的推荐剂量为每3周90mg/m²；既往治疗较少的患者可采用120mg/m²治疗，肝功能不全或骨髓储备临界的患者初始剂量应减至70mg/m²。在霍奇金病、肝癌和食管表皮样癌中观察到治疗活性。在白血病中研究了各种给药方案。II期评估的推荐剂量为每日120mg/m²，持续5天，每日30分钟输注。在此剂量下，观察到恶心、呕吐、粘膜炎、脱发和肝毒性。在急性髓性白血病、急变期慢性粒细胞白血病和慢性淋巴细胞白血病中观察到治疗活性。有必要对该药物进行进一步的临床试验。
