Harringtonine (HT) is a new antitumor agent reported to be active in patients with leukemia and lymphoma. The interaction of HT with various antitumor agents was studied in vitro using a human acute myelogenous leukemia cell line KG-1. For the analysis of the drug - drug interaction at the cellular level, Steel proposed the concept of an envelope of additivity. Using this concept, the effect of a two drug combination can be classified as supraadditive (enhancement of the effect), non-interactive (additive), subadditive, and protective (antagonistic). Combination of HT and cytosine arabinoside or HT and dexamethasone produced only additive effects. Combination of HT and methotrexate was subadditive. For HT plus adriamycin or HT plus 5-fluorouracil, data points indicated both subadditive and protective interaction. HT plus acivicin or HT plus L-asparaginase combinations were found to be protective of each other. None of the seven agents produced supraadditive interaction. These results may provide the basis for selecting sequential rather than concurrent combinations which include HT for the treatment of leukemia in man.
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