RATIONALE FOR DIFFERENT APPROACHES TO COMBINED MELPHALAN AND HYPERTHERMIA IN REGIONAL ISOLATED PERFUSION

The addition of hyperthermia (HT) to regional isolated perfusion (RIP) with Melphalan theoretically has two advantages. Firstly, heat can se lectively kill cells in poorly vascularised areas that are usually not reached by the drug. Secondly, in vitro data have revealed that the e ffect of Melphalan is enhanced at temperatures 39-45 degrees C. Howeve r, for the simultaneous application of Melphalan and HT, as it is give n in most institutes, both normal and tumour tissues within the volume are treated with both modalities. It is unclear whether-for the same heat dose-the cytoxicity of Melphalan is enhanced more in tumour tissu e than in normal tissues. As the applied dose of Melphalan in RIP is s elected on maximum acceptable toxicity, any enhancement of toxicity is undesired. Indeed, Melphalan application at temperatures >41 degrees C has resulted in unacceptable toxicity. In most institutes, the hyper thermia dose is reduced in comparison to application as a single-modal ity treatment, to allow simultaneous combination without unacceptable toxicity. In this review, the rationale for two different approaches i s summarised which may make it possible to improve the benefit from th e theoretical advantage of the use of HT in RIP. It is meant to stimul ate discussion as a possible first step in the design of new treatment protocols. (C) 1997 Elsevier Science Ltd.