Dose-finding study of valspodar (PSC 833) with daunorubicin and cytarabine to reverse multidrug resistance in elderly patients with previously untreated acute myeloid leukemia

The Hematology Journal : the Official Journal of the European Haematology Association
P SonneveldB Löwenberg

Abstract

This trial was designed to determine the maximum tolerated dose of intravenous daunorubicin (DNR) in combination with valspodar and to test the feasibility of P-glycoprotein modulation using valspodar in elderly patients with previously untreated acute myelogenous leukemia receiving standard induction chemotherapy. Patients > or =60 years of age with previously untreated AML received valspodar (10 mg/kg/24 h by continuous intravenous infusion [CIV] on days 1-4 with a 2-mg/kg loading dose on day 1) in conjunction with two cycles of induction chemotherapy consisting of cytarabine (200 mg/m(2) CIV on days 1-7), and DNR (35 mg/m(2) [cohort 1] or 45 mg/m(2) [cohort 2] on days 1-3, intravenous bolus). Patients were assessed for dose-limiting toxicities (DLT), response rate, event-free and overall survival, and pharmacokinetics of valspodar and DNR. Valspodar was well tolerated at the lower DNR dose level (ie, 35 mg/m(2)) resulting in a 21% rate of DLT and only three toxic deaths. Treatment-related mortality was unacceptably high at the 45 mg/m(2) DNR dose level. The complete response rate was 49% overall and similar in both cohorts. The median overall survival of patients was 333 days in cohort 1 compared to 98 days in cohort 2. At b...Continue Reading

Citations

Jun 13, 2002·Reviews in Clinical and Experimental Hematology·Alan K Burnett
Jun 7, 2003·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·C A RodriguesM Yamamoto
Mar 17, 2001·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·R DorrA F List
Dec 13, 2019·British Journal of Haematology·Alan K BurnettNigel Russell
Mar 18, 2009·British Journal of Haematology·Alan K BurnettUNKNOWN United Kingdom National Cancer Research Institute Haematological Oncology Study Group
Sep 24, 2013·Expert Opinion on Drug Metabolism & Toxicology·Ana Espirito Santo, Rui Medeiros
May 18, 2001·Best Practice & Research. Clinical Haematology·P Sonneveld, A F List

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