title: Rationale for different approaches to combined melphalan and hyperthermia in regional isolated perfusion.
abstract: The addition of hyperthermia (HT) to regional isolated perfusion (RIP) with Melphalan theoretically has two advantages. Firstly, heat can selectively kill cells in poorly vascularised areas that are usually not reached by the drug. Secondly, in vitro data have revealed that the effect of Melphalan is enhanced at temperatures 39-45 degrees C. However, for the simultaneous application of Melphalan and HT, as it is given 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 cytotoxicity of Melphalan is enhanced more in tumour tissue than in normal tissues. As the applied dose of Melphalan in RIP is selected 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 hyperthermia dose is reduced in comparison to application as a single-modality treatment, to allow simultaneous combination without unacceptable toxicity. In this review, the rationale for two different approaches is summarised which may make it possible to improve the benefit from the theoretical advantage of the use of HT in RIP. It is meant to stimulate discussion as a possible first step in the design of new treatment protocols.
authors.affiliation: Department of Hyperthermia, University Hospital Rotterdam/Dr Daniel den Hoed Cancer Center, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: van der Zee
authors.forename: B B
authors.initials: BB
authors.lastname: Kroon
authors.forename: O E
authors.initials: OE
authors.lastname: Nieweg
authors.forename: S A
authors.initials: SA
authors.lastname: van de Merwe
authors.forename: H H
authors.initials: HH
authors.lastname: Kampinga
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D010478:Chemotherapy, Cancer, Regional Perfusion; D003131:Combined Modality Therapy; D006801:Humans; D006979:Hyperthermia, Induced; D008545:Melanoma / Q000188:drug therapy / Q000628:therapy*; D008558:Melphalan / Q000627:therapeutic use*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan