Response of peritoneal solid tumours after intraperitoneal chemohyperthermia treatment with cisplatin or carboplatin.
The combination of heat and chemotherapy was studied in an intraperitoneal tumour model. Rats bearing peritoneal CC531 tumours (2-6 mm) were treated i.p. with cDDP or CBDCA [maximal tolerated dose (MTD)] in combination with regional hyperthermia (41.5 degrees C, 1 h) of the peritoneal cavity. The addition of hyperthermia to the i.p. treatment led to a decrease in the MTD of cDDP by 33.3% at 41.5 degrees C. This was due to increased nephrotoxicity. The MTD of CBDCA did not change as a result of hyperthermia treatment. The chemo-hyperthermia treatment resulted in more cDDP or CBDCA DNA adducts in peritoneal tumours after the combined treatment than after chemotherapy alone. The increased tumour platinum concentrations, rising from 1.3 micrograms Pt g-1 tumour at 37 degrees C to 5.4 micrograms Pt g-1 tumour at 41.5 degrees C for cDDP and from 0.2 microgram Pt g-1 tumor to 0.7 microgram Pt g-1 tumour at 41.5 degrees C for CBDCA, contributed considerably to the enhanced numbers of cDDP or CBDCA DNA adducts. As a result of the latter, i.p. chemotherapy combined with regional hyperthermia led to an increase in tumour growth delay (TGD) after increasing the temperature to 41.5 degrees C for cDDP 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 temperatures led to increased cytotoxicity.
Los
G
G
The Netherlands Cancer Institute, Division of Experimental Therapy, Amsterdam.
van Vugt
M J
MJ
Pinedo
H M
HM
D000230:Adenocarcinoma / Q000378:metabolism / Q000628:therapy*; D000818:Animals; D016190:Carboplatin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002945:Cisplatin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000378:metabolism / Q000628:therapy; D003131:Combined Modality Therapy; D003404:Creatinine / Q000097:blood; D006979:Hyperthermia, Induced; D008297:Male; D010534:Peritoneal Neoplasms / Q000378:metabolism / Q000628:therapy*; D051381:Rats; D013696:Temperature; D014407:Tumor Cells, Cultured
D003404:Creatinine; D016190:Carboplatin; D002945:Cisplatin