Phase I trial of homoharringtonine administered as a 5-day continuous infusion.
Homoharringtonine (HHT) has substantial cytotoxic activity against cell lines of experimental tumors. Moreover, the drug has been used extensively in the People's Republic of China for the treatment of patients with acute leukemia. Since rapid injections of HHT can produce serious hypotension and cardiac arrhythmias, we evaluated HHT administered as a continuous infusion for 5 days in patients with advanced cancer. Thirty-one patients were treated with HHT at doses which ranged from 0.2 to 3.75 mg/m2/day. Myelosuppression (both leukopenia and thrombocytopenia) was the dose-limiting toxic reaction. Platelet recovery was delayed in five patients; the median time to platelet nadir was 31 days in patients treated at the highest dose level. Sinus tachycardia occurred frequently, but the relation of this effect to drug administration was uncertain. Serious cardiac arrhythmias and hypotension were not observed using this schedule. We conclude that HHT can be safely administered as a continuous infusion. A daily dose of 3.25 mg/m2 x 5 days is recommended for phase II studies.
D000328:Adult; D000368:Aged; D000470:Alkaloids / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D004341:Drug Evaluation; D006248:Harringtonines / Q000008:administration & dosage* / Q000633:toxicity; D000077863:Homoharringtonine; D006801:Humans; D007263:Infusions, Parenteral; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*
D000470:Alkaloids; D006248:Harringtonines; D000077863:Homoharringtonine