homoharringtonine and Hyperglycemia

Homoharringtonine (HHT) has been reported to induce hyperglycemia. This report describes a study conducted to characterize the effect of HHT on insulin production and action. Our data indicate that HHT-induced hyperglycemia results from the development of insulin resistance. A review of the literature suggests that patients receiving HHT continuous infusions of 5 mg/m2/d or greater and patients greater than 10 years of age may be at increased risk for the development of HHT-induced hyperglycemia. We recommend that patients with these risk factors, as well as diabetic patients and patients concurrently receiving asparaginase and/or prednisone, have their blood glucoses routinely monitored for hyperglycemia.

Topics: Acute Disease; Alkaloids; Antineoplastic Agents, Phytogenic; Blood Glucose; C-Peptide; Drug Evaluation; Harringtonines; Homoharringtonine; Humans; Hyperglycemia; Infusions, Intravenous; Insulin; Insulin Resistance; Leukemia; Risk Factors; Time Factors

Homoharringtonine (HHT) is a new plant alkaloid originally isolated in the People's Republic of China. Preliminary studies have suggested antitumor activity in several neoplastic diseases. We treated 49 patients with relapsed or resistant acute leukemia with escalating doses of homoharringtonine administered by continuous infusion. Three dose levels were examined: 5 mg/m2 for seven days, 7 mg/m2 for seven days, and 5 mg/m2 for nine days. Of 28 patients with acute nonlymphoblastic leukemia who received cumulative doses of 45 to 49 mg/m2, seven patients (25%) achieved complete remission. Four of these remissions occurred in a subset of ten patients previously resistant to two or more induction attempts with conventional chemotherapy. There were no remissions in three patients with secondary leukemia or in seven patients with acute lymphoblastic leukemia. Reversible hypotension, fluid retention, diarrhea, and tumor lysis syndrome were the major toxic effects of this treatment. Our results indicate that homoharringtonine is an effective new drug for the treatment of acute nonlymphoblastic leukemia and that this drug does not share cross-resistance with conventional antileukemic agents. The recommended dose is 5 mg/m2/d administered by continuous infusion for nine days.

Topics: Acute Disease; Adolescent; Adult; Aged; Alkaloids; Antineoplastic Agents; Bone Marrow; Bone Marrow Transplantation; Drug Evaluation; Harringtonines; Homoharringtonine; Humans; Hyperglycemia; Hypotension; Infusions, Parenteral; Leukemia; Leukocyte Count; Middle Aged; Platelet Count