Sadowitz P D, Dubowy R, Souid A, Pollock B H, Weinstein H, Parmley R T, Bowman W P, Land V, Vats T, Pratt C
Department of Pediatrics, State University of New York, Health Science Center, Syracuse.
J Clin Oncol. 1994 Sep;12(9):1969-73. doi: 10.1200/JCO.1994.12.9.1969.
The purpose of this phase I study was to determine the toxicities and response to continuous infusion carboplatin in combination with a fixed dose of etoposide (VP-16) in children with refractory acute leukemia.
From January 1989 to February 1992, 20 patients received 28 courses of treatment. Each course of treatment consisted of a 1-hour intravenous (IV) infusion of VP-16 100 mg/m2/d for 5 days, followed by a 23-hour IV infusion of carboplatin each day. The initial, total 5-day dose of carboplatin (1,000 mg/m2) was escalated by 250- to 375-mg increments to a final, total dose of 1,875 mg/m2 over 5 days.
Significant marrow suppression was observed in all patients, with prolonged marrow aplasia at the 1,875-mg/m2 dose level. Grade III diarrhea occurred in three patients; 10 patients experienced life-threatening infection and three had severe thrombocytopenic bleeding. Major marrow responses (two complete remissions and two partial remissions) occurred in four patients (20%).
In view of the apparent antileukemic efficacy and minimal extramedullary toxicity, carboplatin deserves further study in a phase II trial.
本I期研究旨在确定难治性急性白血病患儿连续输注卡铂联合固定剂量依托泊苷（VP - 16）的毒性及反应。
1989年1月至1992年2月，20例患者接受了28个疗程的治疗。每个疗程包括VP - 16 100 mg/m²/d静脉输注1小时，共5天，随后每天进行23小时卡铂静脉输注。卡铂初始5天总剂量（1000 mg/m²）以250至375 mg的增量逐步增加至最终5天总剂量1875 mg/m²。
所有患者均观察到明显的骨髓抑制，在1875 mg/m²剂量水平出现了长期的骨髓再生障碍。3例患者发生III级腹泻；10例患者发生危及生命的感染，3例患者出现严重血小板减少性出血。4例患者（20%）出现主要骨髓反应（2例完全缓解和2例部分缓解）。
鉴于明显的抗白血病疗效和最小的髓外毒性，卡铂值得在II期试验中进一步研究。
