Van Echo D A, Chiuten D F, Gormley P E, Lichtenfeld J L, Scoltock M, Wiernik P H
Cancer Res. 1979 Oct;39(10):3881-4.
4'-(9-Acridinylamino)methanesulfon-m-anisidide (m-AMSA, NSC 249992), an acridine derivative, was given to 28 patients with solid tumors and one patient with Hodgkin's disease in a Phase I clinical trial. The dose schedule used was a single dose given every 14 days for three doses. The amount given ranged from 10 to 120 mg/sq m/dose. Dose-limiting toxicity was moderate to severe leukopenia which occurred at and above 70 mg/sq m. Thrombocytopenia was infrequent and did not require transfusion. Nonhematological side effects were mild and included nausea, vomiting, local irritation, and fever. Antineoplastic activity was noted in liposarcoma, adenocarcinoma of unknown primary origin, and squamous carcinoma of unknown primary origin (one patient each). Pharmacokinetics studies were done in 19 patients. Total m-AMSA and free m-AMSA concentrations showed a biphasic distribution with an initial rapid phase of t1/2 = 10 to 15 min for both, and a second slow phase of t1/2 = 8 to 9 hr for total m-AMSA and 3 hr for free m-AMSA. Phase II studies with m-AMSA, in hematological cancers are warranted, since its most consistent effect is on leukocytes. The recommended dosages for solid-tumor Phase II studies are 70 mg/sq m for good-risk patients and 50 mg/sq m for poor-risk patients, given as a single dose every other week, or 120 mg/sq m for poor-risk patients for the single-dose every-3-week schedule.
4'-(9-吖啶基氨基)甲磺酰间茴香胺（m-AMSA，NSC 249992），一种吖啶衍生物，在一项I期临床试验中给予了28例实体瘤患者和1例霍奇金病患者。使用的给药方案是每14天给予单次剂量，共给药三次。给药量范围为10至120mg/平方米/剂量。剂量限制性毒性为中度至重度白细胞减少，发生在70mg/平方米及以上剂量时。血小板减少不常见，无需输血。非血液学副作用较轻，包括恶心、呕吐、局部刺激和发热。在脂肪肉瘤、原发灶不明的腺癌和原发灶不明的鳞状细胞癌（各1例患者）中观察到抗肿瘤活性。对19例患者进行了药代动力学研究。总m-AMSA和游离m-AMSA浓度呈双相分布，两者的初始快速相t1/2 = 10至15分钟，总m-AMSA的第二缓慢相t1/2 = 8至9小时，游离m-AMSA的第二缓慢相t1/2 = 3小时。鉴于m-AMSA对白细胞的作用最为一致，有必要对血液系统癌症进行m-AMSA的II期研究。实体瘤II期研究的推荐剂量为，低风险患者70mg/平方米，高风险患者50mg/平方米，每两周给予单次剂量；或高风险患者每三周单次剂量为120mg/平方米。
