Gams R A, Ostroy F, Bender J F, Grillo-López A J
Invest New Drugs. 1985;3(4):383-8. doi: 10.1007/BF00170762.
Ametantrone acetate is an intensely blue anthracenedione undergoing clinical trials in man. In this Phase I study, 20 patients received 39 courses of drug as a single IV dose given daily for five days and repeated every three weeks (21 days). Dosage escalations proceeded from 15 mg/m2 to 35 mg/m2. Predictable and reversible leukopenia was the dose limiting toxicity. One previously untreated patient with renal cell carcinoma metastatic to the lungs and right arm experienced a partial response of 51 days duration. Nine patients had pharmacokinetic studies performed during the study. Ametantrone was extensively distributed (apparent volume of distribution, 26.3 l/m2) and demonstrated a short half-life (harmonic mean half-life, 0.38 hour). The maximum tolerated dose in this study was 35 mg/m2. Recommended doses for Phase II trials are 30 mg/m2 in good risk patients and 25 mg/m2 in poor risk patients. Because of the partial response seen in one patient with renal cell carcinoma, Phase II trials should include this tumor category in order to better define the activity of ametantrone in this disease. In addition, since the total amount of drug that could be given to patients receiving the five day schedule (125-150 mg/m2) was approximately the same amount that could be administered as a single dose (140 mg/m2), it would appear that the only advantage of the daily times five day dosage schedule would be in the lower incidence of bluish skin discoloration.
醋酸阿美蒽醌是一种深蓝色蒽二酮，正在进行人体临床试验。在这项I期研究中，20例患者接受了39个疗程的药物治疗，静脉单剂量给药，每日1次，共5天，每3周（21天）重复1次。剂量从15mg/m²逐步递增至35mg/m²。可预测且可逆的白细胞减少是剂量限制性毒性。1例既往未接受过治疗、肺和右臂转移的肾细胞癌患者出现了持续51天的部分缓解。9例患者在研究期间进行了药代动力学研究。阿美蒽醌分布广泛（表观分布容积为26.3l/m²），半衰期短（调和平均半衰期为0.38小时）。本研究中的最大耐受剂量为35mg/m²。II期试验的推荐剂量为，低风险患者30mg/m²，高风险患者25mg/m²。鉴于1例肾细胞癌患者出现了部分缓解，II期试验应纳入该肿瘤类型，以便更好地明确阿美蒽醌在该疾病中的活性。此外，由于接受5天给药方案的患者可给予的药物总量（125 - 150mg/m²）与单剂量给药（140mg/m²）的总量大致相同，因此每日5次给药方案的唯一优势似乎在于皮肤变蓝的发生率较低。
