Vats T, Kamen B, Krischer J P
University of Kansas Medical School, Kansas City.
Invest New Drugs. 1991 Nov;9(4):333-7. doi: 10.1007/BF00183575.
ICRF-187 is the (+) enantiomer of the racemic mixture razoxane (ICRF-159). This compound is much more water soluble and thus could be formulated for parental use. The maximum tolerated dose in children after phase I trials was determined to be 3500 mg/M2/day x 3 days. A phase II trial of ICRF-187 was done in 21 children with solid tumors and 35 children with acute leukemia. All these patients were less than 21 years of age, had recovered from previous chemotherapy, had normal liver and kidney functions, and had a life expectancy of greater than 4 weeks. ICRF-187 was administered at a dose of 3 g/M2/day for 3 days as a 4 hour infusion each day. In patients with leukemia, no objective response was seen in the bone marrow although a few patients had a decrease in peripheral blast count. There were no measurable responses seen in patients with a solid tumor. ICRF-187 was well tolerated. The major toxicity was hematopoietic depression. Significant but rare toxicities included moderate to severe nausea and vomiting, and elevation of bilirubin and transaminases. Although inactive in the current study, ICRF-187 might be more active in another schedule.
ICRF - 187是消旋混合物丙亚胺（ICRF - 159）的（+）对映体。该化合物的水溶性更强，因此可配制成供肠胃外使用的剂型。I期试验后确定儿童的最大耐受剂量为3500mg/M²/天，共3天。对21例实体瘤患儿和35例急性白血病患儿进行了ICRF - 187的II期试验。所有这些患者年龄均小于21岁，已从先前的化疗中恢复，肝肾功能正常，预期寿命超过4周。ICRF - 187以3g/M²/天的剂量给药，共3天，每天静脉输注4小时。在白血病患者中，尽管有少数患者外周原始细胞计数下降，但骨髓中未观察到客观缓解。实体瘤患者中未观察到可测量的缓解。ICRF - 187耐受性良好。主要毒性为造血抑制。显著但罕见的毒性包括中度至重度恶心和呕吐，以及胆红素和转氨酶升高。尽管在当前研究中无活性，但ICRF - 187在另一种给药方案中可能更具活性。
