Schedule-dependent combined sensitivity testing of anti-cancer agents in human gastric carcinoma cell lines

The efficacy of combination chemotherapy for gastric carcinoma has been uns atisfactory, although the prognosis of advanced and recurrent disease has i mproved with the introduction of cisplatin (CDDP). This study examines the effect of the anti-cancer therapies CDDP, doxorubicin (ADM) and etoposide ( VP-16) on the cell cycle and their cytotoxicity against two gastric carcino ma cell lines: MKN-28 (well differentiated) and MKN-45 (poorly differentiat ed). The treatments have different cytocidal mechanisms, and they were stud ied in dual combinations. For all combinations studied, cytotoxicity agains t MKN-45 was higher than against MKN-28. for ADM plus CDDP, or ADM plus VP- 16, cytotoxicity was higher in patients pretreated with ADM than other regi mens. The highest anti-tumour activity against both cell lines was obtained with ADM followed by CDDP (we have obtained good clinical results with thi s regimen). Schedule-dependent combined sensitivity testing of anti-cancer agents will be useful for the clinical application of therapies.