Evaluation of hypoxia and acidosis on the cytotoxicity of the stereoisomers of tetraplatin at normal and hyperthermic temperatures

Abstract

Tetraplatin is a second-generation platinum analogue that will be introduced into clinical trials during 1990. We have evaluated the cytotoxicity of tetraplatin and its stereoisomers under a variety of conditions in a human solid tumour cell line (A549). The d-trans stereoisomer of tetraplatin is the most cyutotoxic form of the drug under all conditions examined. Simultaneous treatment with hyperthermia (43°C) resulted in a greater than 1 log increase in cytotoxicity over tetraplatin (10 ä;g/ml) alone. Lowering the pH of the media from 7.4 to 6.4 did not significantly modify the cytotoxicity of tetraplatin at 37°C or at 43°C. Under acidic pH (6.4) hypoxia did not alter the cytotoxicity of tetraplatin at 37°C or 43°C. These results indicate a potential therapeutic advantage of combining tetraplatin chemotherapy with hyperthermia, which appears to be uneffected by acidic andlor hypoxic conditions.

Key Words:

• Hyperthermia
• tetraplatin
• hypoxia
• thermochemotherapy