A phase II study employing combination regimens containing KRN8602 in drug-resistant acute myeloid leukemia and acute lymphoblastic leukemia

We conducted a phase II multicenter study in order to evaluate the efficacy and toxicity of two combination regimens containing KRN8602 (MX2) for drug -resistant acute myeloid leukemia (AML) and acute lymphoblastic leukemia (A LL), AML was treated with KRN8602, 15 mg/m(2) i.v. push for 5 days, and cyt arabine (AraC), 100 mg/m(2) by 24 h coutinuous infusion for 7 days. ALL was treated with KRN8602, 15 mg/m(2) i.v, push for 5 days, vincristine (VCR), 1.4 mg/m(2) i.v. push, once weekly, and prednisolone (PSL), 40 mg/m2, 3 h i nfusion for 5 days. In AML and ALL, the complete remission (CR) rate was 36 .4% (16 of 44) and 24.1% (seven of 29), and the overall response rate (CR+P R) was 52.3% (23 of 44) and 51.7% (15 of 29), respectively. Among the 29 re lapsed cases of AML, a higher CR rate, 51.7% (15 of 29), was obtained. A hi gh incidence of nausea/vomiting and anorexia was observed, and some patient s experienced central nervous system disorders and peripheral neuropathy. T here was a low incidence of severe neurotoxicities; all other toxicities we re manageable, KRN8602 was found to overcome drug resistance clinically, co nfirming results based on the preclinical studies. We conclude that KRN8602 is an effective novel anthracycline for drug-resistant acute leukemias. [( C) 1999 Lippincott Williams & Wilkins.]