EXPERIMENTAL COMBINATION CHEMOTHERAPY OF PIRARUBICIN WITH VARIOUS ANTITUMOR DRUGS AGAINST P388 MURINE LEUKEMIA

We have examined the therapeutic effects of combination therapy of pir arubicin ((2 '' R)-4'-O-tetrahydropyranyladriamycin, THP) with various antitumor agents against P388 murine leukemia. THP showed a high anti tumor activity in combination with various antitumor drugs, especially with cyclophosphamide (CPM), cisplatin (CDDP), mitomycin C (MMC), eno citabine (BHAC), vindesine (VDS) or methotrexate (MTX). The effects of combination therapy depended on the order of administration of THP an d combined drugs. THP-preceding treatment gave more synergistic effect s in combination with 5-fluorouracil (5-FU) or MTX. THP-preceding or s imultaneous treatment with etoposide (ETP) indicated the higher synerg istic activity than ETP-preceding one. Moreover, THP showed much highe r synergistic effects in any order of the combination with CPM, CDDP, MMC, BHAC, VDS or MTX. These results suggest that THP possesses a ther apeutic usefulness clinically in combination with various antitumor dr ugs, if the selection of drugs combined with THP and the order of admi nistration are suitable.