Antitumor activity of hyperthermia alone or in combination with cisplatin and melphalan in primary cultures of human malignant melanoma

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Abstract
The effects of heat and the interaction between hyperthermia and alkylating agents, such as cisplatin (CDDP) and melphalan (L‐PAM) in human malignant melanoma biopsies have been investigated by a short‐term assay based upon the inhibition of H‐thymidine incorporation. Cell suspensions from 50 cutaneous and lymph nodal metastases were heated at 40.5°C or at 42°C for 1 h. There were significant antiproliferative effects due to heat in 10% of the tumors exposed to 40.5°C and 34% to 42°C. Thermal resistance was evident in 73% (at 40.5°C) and 54% (at 43°C) of tumors, and there was significant enhancement of cell growth in 17% and 12% of tumors. The combined effects of hyperthermia and drugs were studied on 36 tumors. Cell suspensions were exposed to different concentrations of CDDP or L‐PAM for 1 h at 40.5°C and 42°C. Synergy between heat and CDDP was observed in 7% of cases treated with the lowest drug dose and 38% of cases treated with the highest (40.5°C), with only a slight increase in the frequency of synergy at 42°C. Synergy between heat and L‐PAM was also observed in 12% to 44% of tumors at 42°C as a function of drug concentration.