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

Int J Hyperthermia. 1992 Nov-Dec;8(6):783-94. doi: 10.3109/02656739209005026.

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 degrees C) 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 degrees C, 30 min) produced greater potentiation of the cytotoxicity of three platinum complexes than did whole-body hyperthermia (42 degrees C, 60 min). Only the complete treatments including whole-body hyperthermia/etanidazole 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Combined Modality Therapy
  • Creatinine / blood
  • Etanidazole / administration & dosage
  • Etanidazole / therapeutic use
  • Fibrosarcoma / drug therapy*
  • Fibrosarcoma / therapy*
  • Hyperthermia, Induced* / adverse effects
  • Kidney / drug effects
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / secondary
  • Lung Neoplasms / therapy*
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / therapeutic use*
  • Organoplatinum Compounds / toxicity

Substances

  • Organoplatinum Compounds
  • Etanidazole
  • Creatinine