Potentiation of melphalan by systemic hyperthermia in mice: Therapeutic gain for mouse lung microtumours

Abstract

The effect of systemic hyperthermia at 41°C on the response to melphalan (Mel) of KHT and RIF-1 lung microtumours was studied. Mice with KHT micro-tumours were treated on day 3 or 4 after inoculation and mice with RIF-1 microtumours on day 4. Results were compared with previously published data for 300–600 mm³ leg tumours and normal marrow stem cells, and therapeutic ratios (TR) were calculated. Therapeutic gain was found for both tumours but in RIF-1 at higher doses only, with TRs from 1.1 to 1.6 for KHT microtumours and from 0.8 to 1.4 for RIF-1. TR values were rather smaller for lung microtumours than leg tumours but the change in slope of the Mel dose response curve by heat was very similar. The results are discussed in the light of the likely difference of tumour milieu between leg tumours and lung microtumours.

Key Words:

• melphalan
• systemic hyperthermia
• microtumour
• therapeutic gain
• murine