Phase I study of cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, combined with cytarabine in patients with refractory leukemia
Phase I study of cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, combined with cytarabine in patients with refractory leukemia
复制标题
DOI：
10.1158/1078-0432.ccr-05-1070
复制
发表时间：
2005-11-01
影响因子：
11.5
通讯作者：
Kantarjian, H
中科院分区：
文献类型：
--
作者：
Giles, F;Verstovsek, S;Kantarjian, H
Purpose: Cloretazine (VNP40101M) is a novel sulfonylhydrazine alkylating agent with significant antileukemia activity. A phase 1 study of cloretazine combined with cytarabine (1-beta-D-arabinofuranosylcytosine, ara-C) was conducted in patients with refractory disease.Design: Ara-C was given i.v. at a fixed dose of 1.5 gm/m(2)/d by continuous infusion for 4 days (patients ages < 65 years at time of diagnosis) or 3 days (patients ages 65 years). Cloretazine was given i.v. over 15 to 60 minutes on day 2 at a starting dose of 200 mg/m(2), with escalation in 100 mg/m(2) increments in cohorts of three to six patients until a maximum tolerated dose was established. The DNA repair enzyme O-6-alkylguanine DNA alkyltransferase (AGT) was measured at baseline.Results: Forty patients, including 32 with acute myeloid leukemia, received 47 courses of treatment. Complete responses were seen at cloretazine dose levels of >= 400 mg/m(2) in 10 of 37 (27%) evaluable patients, and in this patient subset, AGT activity was significantly lower in patients that responded to treatment than in patients who did not (P
