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 unsatisfactory, although the prognosis of advanced and recurrent disease has improved 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 carcinoma cell lines: MKN-28 (well differentiated) and MKN-45 (poorly differentiated). The treatments have different cytocidal mechanisms, and they were studied in dual combinations. For all combinations studied, cytotoxicity against 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 regimens. The highest anti-tumour activity against both cell lines was obtained with ADM followed by CDDP (we have obtained good clinical results with this regimen). Schedule-dependent combined sensitivity testing of anti-cancer agents will be useful for the clinical application of therapies.