Thermochemotherapy with cis-platinum, CCNU, BCNU, chlorambucil and melphalan on murine marrow and two tumours: therapeutic gain for melphalan only

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Abstract
The magnitude of potentiation by whole body hyperthermia (45 min at 41.degree. C) of cis-platinum (DDP), CCNU [Lomustine], BCNU [carmustine], chlorambucil and melphalan (Mel) on 2 tumors was compared with that on marrow in C3H mice. Drug damage was assayed in the KHT tumor by growth delay and in the RIF-1 tumor by clonogenic cell survival 24 h after treatment and/or by growth delay. Toxicity to marrow stem cells was assayed 24 h after treatment, by the spleen colony technique. When drug was given at the start of heating, all drugs were potentiated both in tumor and marrow to varying degrees. However, there was no therapeutic gain for the combined treatment with DDP on RIF-1, with CCNU or BCNU on KHT, or with CHL on either RIF-1 or KHT. Therapeutic ratios for Mel of 1.9-2.0 for KHT and of 1.1-1.8 in RIF-1 were measured over the dose range 7.5-15.0 mg/kg in unheated animals, indicating net therapeutic gain under these conditions. An absolute therapeutic gain was found for Mel in KHT when Mel was given 30 min before the start of heat.