Whole-body hyperthermia as an adjuvant to treatment with platinum complexes with or without etanidazole in mice bearing the Lewis lung carcinoma or the FSaLL fibrosarcoma

Abstract

The response of s.c. primary and metastatic Lewis lung carcinoma to five antitumour platinum complexes with or without tolerable whole-body hyperthermia (60 min to reach temperature then 60 min at 42°) was examined. The whole-body hyperthermia treatment produced about 2.8 days of tumour growth delay in the s.c. tumours. The addition of whole-body hyperthermia to treatment with each of the platinum complexes was well tolerated by the animals and increases of 1.6–2.0-fold in tumour growth delay resulted with the combined treatment compared with the platinum complexes alone. The combination of etanidazole (1 g/kg) and the platinum complexes followed by whole-body hyperthermia produced marked increases in tumour growth delay ranging from 2.5– to 3.6-fold over the growth delays obtained with the platinum complexes alone. FSaLLC tumour cell survival and bone marrow CFU-GM experiments indicated that local hyperthermia (43°, 30 min) produced greater potentiation of the cytotoxicity of three platinum complexes than did whole-body hyperthermia (42°, 60 min). Only the complete treatments including whole-body hyperthermidetanidaole and the platinum complexes were effective in significantly reducing the numbers of lung metastases formed from s.c. primary tumours. Serum urea nitrogen and creatinine levels were monitored over a time-course post-treatment. Although some treatment combinations caused elevations in these normal tissue parameters by day 12 post-treatment both serum urea nitrogen and serum creatinine returned to the levels of the untreated control animals.

Key Words:

• Whole-body hyperthermia
• platinum complexes
• etanidazole
• lung metastases