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Keywords:

  • carboplatin;
  • leukemia;
  • acute lymphoblastic leukemia;
  • acute myelogenous leukemia

Abstract

Background. Carboplatin is an analogue of cisplatin with less nonhematologic toxicity and a similar spectrum of antineoplastic activity as the parent compound. Although cisplatin has not been found to be an active agent in leukemia, carboplatin induced complete remissions in adults with acute myelogenous leukemia (AML). Therefore, a pediatric Phase I study in acute leukemia was performed.

Methods. Between January 1988 and April 1990, the Childrens Cancer Group performed a Phase I study of carboplatin administered by a 5-day continuous intravenous infusion to children with acute leukemia in bone marrow relapse.

Results. Mild to moderate glomerular and tubular nephrotoxicity was seen in most patients treated at the initial dose level of 336 mg/m2/day. Therefore, patients at the second dose level were treated at 270 mg/m2/day. At this level, one patient died of acute hepatic necrosis and hepatic encephalopathy, and a second patient had presumed hemorrhagic cystitis develop. The third dose level tested, 216 mg/m2/day, was not associated with unacceptable toxic effects and was considered the maximum tolerated dose (dose-limiting toxicity was not observed). Within the confines of this Phase I study, anti-leukemic activity was shown in patients with acute lymphoblastic leukemia (ALL) and AML.

Conclusions. In this pediatric Phase I trial of carboplatin in acute leukemia, glomerular and tubular nephrotoxicity was considered dose-limiting. In addition, hepatotoxicity and hemorrhagic cystitis were observed. Anti-leukemic activity was shown in patients with ALL and AML. The recommended Phase II dose is 216 mg/m2/day by 5-day continuous intravenous infusion.