RESPONSE OF PERITONEAL SOLID TUMORS AFTER INTRAPERITONEAL CHEMOHYPERTHERMIA TREATMENT WITH CISPLATIN OR CARBOPLATIN

The combination of heat and chemotherapy was studied in an intraperito neal tumour model. Rats bearing peritoneal CC531 tumours (2-6 mm) were treated i.p. with cDDP or CBDCA [maximal tolerated dose (MTD)] in com bination with regional hyperthermia (41.5 degrees C, 1 h) of the perit oneal cavity. The addition of hyperthermia to the i.p. treatment led t o a decrease in the MTD of cDDP by 33.3% at 41.5 degrees C. This was d ue to increased nephrotoxicity. The MTD of CBDCA did not change as a r esult of hyperthermia treatment. The chemo-hyperthermia treatment resu lted in more cDDP or CBDCA DNA adducts in peritoneal tumours after the combined treatment than after chemotherapy alone. The increased tumou r platinum concentrations, rising from 1.3 mu g Pt g(-1) tumour at 37 degrees C to 5.4 mu g Pt g(-1) tumour at 41.5 degrees C for cDDP and f rom 0.2 mu g Pt g(-1) tumor to 0.7 mu g Pt g(-1) tumour at 41.5 degree s C for CBDCA, contributed considerably to the enhanced numbers of cDD P or CBDCA DNA adducts. As a result of the latter, i.p. chemotherapy c ombined with regional hyperthermia led to an increase in tumour growth delay (TGD) after increasing the temperature to 41.5 degrees C for cD DP and CBDCA (by 40 days for cDDP, 22 days for CBDCA). These data were in agreement with the in vitro findings, i.e. that higher temperature s led to increased cytotoxicity.