Effects of carboplatin in combination with other anticancer agents on human leukemia cell lines

Abstract

In vitro studies with drug combinations of carboplatin and other anticancer agents were carried out in MOLT-3 human lymphoblastic leukemia and HL-60 human promyelocytic leukemia cell lines. Cells were incubated for 3 days in the presence of various concentrations of carboplatin and other drugs and cell growth inhibition was determined by MTT assay. The antitumor effects of the drug combinations at id 50 were analyzed using an improved isobologram. In MOLT-3 cells, supra-additive (synergistic) effects were observed for carboplatin in combination with cytosine arabinoside, mitoxantrone and CPT-11. Additive effects were observed for combinations of carboplatin with bleomycin, daunorubicin, doxorubicin, etoposide, 6-mercaptopurine, and vincristine. Sub-additive and protective (antagonistic) effects were observed with methotrexate. Synergistic or antagonistic effects for combinations of carboplatin and CPT-11, cytosine arabinoside, mitoxantrone and methotrexate were also observed in HL-60 cells. These findings suggest that carboplatin has additive or synergistic cytotoxic effects with most of the agents tested. Determination of the usefulness of these drug combinations awaits appropriate in vivo experiments that should assess both tumorcidal effects and possible increased toxicity. The simultaneous administration of carboplatin and methotrexate would be of little effect. To find optimal schedules for this combination, further pre-clinical studies of various combinations schedule would appear to be warranted.