Vogler W R, Harrington D P, Winton E F, Lazarus H M, Bennett J M, Cassileth P A, Oken M M
Emory University, Atlanta, GA.
Leukemia. 1992 Oct;6(10):1072-5.
Carboplatin is a second-generation platinum complex drug which has demonstrated activity against a variety of neoplasms including acute leukemia, particularly when given by continuous intravenous (i.v.) infusion. Adults with acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL), either refractory or in first or second relapse, were given a continuous i.v. infusion of carboplatin at a dose of 315 mg/m2 daily for 5 days. A second course was given if the bone marrow at day 14 showed persistent leukemia. If the marrow was hypoplastic, treatment was delayed until marrow recovery was documented. Those with residual leukemia were given a second course. Those achieving complete remission (CR) were given an additional course as consolidation. Of the 46 eligible patients entered (36 AML and 10 ALL) eight achieved CR (17%) of which 6 were AML and 2 ALL. Of nine primary refractory patients, two achieved CR, one AML and one ALL. Excluding the inevaluable patients (protocol violations, patient refused further therapy, early deaths prior to day 14, the CR rate was eight of 28 (29%). All except two CRs required two courses of induction. The non-hematologic toxicity was minimal except for renal and auditory toxicity. Renal toxicity greater than grade 2 was seen in 17 patients and was associated with concomitant use of nephrotoxic antibiotics. In two patients, renal failure was a major factor in the cause of death. Ototoxicity was observed in 11 patients, but was grade 3 in only three. There were 18 deaths during the study. Fourteen died of infection, two died of infection and hemorrhage, one died of hemorrhage while aplastic, and one died of other causes. This trial indicates that carboplatin is an active agent in acute leukemia and warrants further investigation.
卡铂是一种第二代铂类复合药物，已证明对包括急性白血病在内的多种肿瘤具有活性，特别是通过持续静脉输注给药时。患有急性髓性白血病（AML）或急性淋巴细胞白血病（ALL）的成人，无论是难治性的还是处于首次或第二次复发阶段，均接受卡铂持续静脉输注，剂量为315mg/m²，每日1次，共5天。如果第14天的骨髓显示仍有白血病，则给予第二个疗程。如果骨髓发育不全，则推迟治疗，直至记录到骨髓恢复。有残留白血病的患者给予第二个疗程。达到完全缓解（CR）的患者给予额外一个疗程作为巩固治疗。在入组的46例符合条件的患者中（36例AML和10例ALL），8例达到CR（17%），其中6例为AML，2例为ALL。在9例原发性难治性患者中，2例达到CR，1例AML和1例ALL。排除不可评估的患者（违反方案、患者拒绝进一步治疗、第14天之前早期死亡），CR率为28例中的8例（29%）。除2例CR外，所有患者均需要两个疗程的诱导治疗。非血液学毒性最小，除了肾毒性和耳毒性。17例患者出现大于2级的肾毒性，这与同时使用肾毒性抗生素有关。2例患者中，肾衰竭是死亡的主要原因。11例患者观察到耳毒性，但只有3例为3级。研究期间有18例死亡。14例死于感染，2例死于感染和出血，1例在再生障碍时死于出血，1例死于其他原因。该试验表明卡铂在急性白血病中是一种活性药物，值得进一步研究。
