Homoharringtonine - History, current research, and future directions

BACKGROUND. Cephalotoxine esters, including homoharringtonine (HHT), have s hown encouraging activity in leukemia in initial studies in China and in la ter studies in the U.S. METHODS. The authors conducted a review of the literature to examine the st udies pertinent to HHT in relation to preclinical studies and Phase I-II tr ials in patients with hematologic malignancies and solid tumors. RESULTS. HHT and analogues appear to induce differentiation and apoptosis. Studies from China reported high response rates in patients with leukemia. Trials in the U.S. using short HHT infusions (3-4 mg/m(2) daily for 5 days) resulted in a high incidence of cardiovascular complications that were red uced using continuous infusion schedules of 3-7 mg/m(2) daily for 5-7 days initially, and later lower dose schedules of 2.5 mg/m(2) daily for 7-14 day s. Results in solid tumors were negative. However encouraging results were reported in patients with acute myeloid leukemia, myelodysplastic syndrome, acute promyelocytic leukemia, and, most important, chronic myeloid leukemi a (CML). In CML patients, HHT has been investigated alone and in combinatio n with interferon-a and low-dose cytarabine in late and early chronic phase s, with positive results. Additional areas of interest include the potentia l use of HHT for the treatment of central nervous system leukemia, polycyth emia vera, and other nonmalignant conditions such as malaria. New semisynth etic preparations and HHT derivatives that bypass multidrug resistance may improve the efficacy and toxicity profiles, and broaden the range of antitu mor efficacy. CONCLUSIONS. HHT and its derivatives appear to have promising activity in h ematologic malignancies, a finding that needs to be pursued. (C) 2001 Ameri can Cancer Society.