DRUG-INTERACTIONS OF 5-FLUOROURACIL WITH EITHER CISPLATIN OR LOBAPLATIN - A NEW, CLINICALLY ACTIVE PLATINUM ANALOG IN ESTABLISHED HUMAN CANCER CELL-LINES

Lobaplatin [1,2-diaminomethylcyclobutane platinum(II)-lactate] is a ne w platinum compound which appears to possess incomplete cross-resistan ce to cisplatin and might have a favorable pattern of side effects. Si nce lobaplatin has activity in esophageal cancer, combination protocol s with 5-fluorouracil (5-FU) are evaluated, In order to assess the mod e of action of lobaplatin when combined with 5-FU, two human cancer ce ll lines were treated with various combinations of 5-FU given for eith er 2 or 24 h and lobaplatin. Drug interactions were evaluated by isobo logram analysis, Lobaplatin showed basically the same interaction patt ern when combined with 5-FU as cisplatin. The combination of either pl atinum analog with a 24 h exposure to 5-FU was superior to a short-ter m 5-FU exposure, Furthermore, when 5-FU was given for 24 h, no additio nal effect of folinic acid was seen. From these data we conclude that cisplatin and lobaplatin show similar interactions with 5-FU. Protract ed infusion schedules of 5-FU appear to be more active than bolus appl ication.