Homoharringtonine in combination with cytarabine for patients with acute myelogenous leukemia.
Homoharringtonine (HHT) is one of several cephalotaxine alkaloids that has shown clinical efficacy in patients with acute myelogenous leukemia (AML). In a phase I trial we evaluated cytarabine 100 mg/m2 by continuous infusion daily for 7 days in combination with four dose levels of HHT ranging from 1.5-5 mg/m2 by continuous infusion daily for 7 days to see if an effective regimen could be developed. Twenty-two patients with relapsed and/or primary refractory AML were treated. Seventeen males and five females were treated, with a median age of 40 years (range 19-63). There were five remissions in 14 patients with relapsed AML and none of eight responders in patients with primary refractory AML. None of the three patients treated at 1.5 mg/m2 dose level of HHT responded. Of three patients treated at the 3 mg/m2 dose level, there was one complete remission. At both 4 mg/m2 and 5 mg/m2, two of eight patients achieved complete remission. Four of the five remissions occurred in patients with acute promyelocytic leukemia. Drug induced pancytopenia was universal, and hypotension and fluid retention were more common at the higher dose levels. Other toxicity was mild and included nausea, vomiting, diarrhea, and mucositis. No significant hepatic, renal, or cardiac toxicity was seen. We conclude that the dose of HHT 4 mg/m2 for 7 days by continuous infusion in combination with cytarabine is safe for patients with AML; and this combination is appropriate for a phase II evaluation.
Feldman
E
E
New York Medical College, Department of Medicine, Valhalla 10595.
Arlin
Z
Z
Ahmed
T
T
Mittelman
A
A
Puccio
C
C
Chun
H
H
Cook
P
P
Baskind
P
P
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols; D003561:Cytarabine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006248:Harringtonines / Q000008:administration & dosage*; D000077863:Homoharringtonine; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012008:Recurrence
D006248:Harringtonines; D003561:Cytarabine; D000077863:Homoharringtonine