Phase I pharmacokinetic study of DUP-937, a new anthrapyrazole.
DUP-937 is a new anthrapyrazole intercalator that inhibits DNA synthesis. A phase I trial was conducted in which DUP-937 was given in an intravenous bolus weekly for 3 weeks. Cycles were repeated every 5 weeks. Twenty men and 13 women with median ECOG performance status of 1 completed 74 cycles. The starting dose was 0.55 mg/m2/week and doses were escalated to 16 mg/m2/week. Non-hematological toxicity was generally mild or moderate and consisted mainly of gastro-intestinal effects, fatigue, alopecia and local reactions. Grade 3 neutropenia was first documented at 7.36 mg/m2 and became more common at higher dose levels. Three of four patients had > or = grade 3 neutropenia at the 16 mg/m2 dose level. Thrombocytopenia was minimal. The dose-limiting toxicity was neutropenia and the maximum tolerated dose was 16 mg/m2 weekly for 3 weeks. Mean area under the curve (AUC) values increased with dose. Linear pharmacokinetics were observed as total body clearance (CLtb), half-life (t1/2) and volume of distribution (Vss) did not change with increasing doses. One partial remission in a patient with prostate carcinoma was documented.
Bélanger
K
K
Department of Medicine, Hôpital Notre-Dame, University of Montréal, Canada.
Jolivet
J
J
Maroun
J
J
Stewart
D
D
Grillo-Lopez
A
A
Whitfield
L
L
Wainman
N
N
Eisenhauer
E
E
D000328:Adult; D000368:Aged; D000880:Anthraquinones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006403:Hematologic Tests; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy*; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*
D000880:Anthraquinones; D000970:Antineoplastic Agents; D011720:Pyrazoles; C046658:teloxantrone