The effect of whole body hyperthermia on 5-fluorouracil pharmacokinetics in vivo and clonogenicity of mammalian colon cancer cells.

Abstract

In a non-randomized pilot study, 10 patients with histological proof of metastatic colorectal adenocarcinoma were treated by hyperthermia/chemotherapy protocol (41,8 degrees C and 1000 mg 5-FU). Plasma levels of 5-FU were determined after single dose at normothermia and hyperthermia. Plasma concentration time course was consistent with a two-compartment pharmacokinetic open model, with first order kinetic and was significantly altered by hyperthermic treatment. Cytotoxicity of 5-FU was substantially enhanced at hyperthermia (41.8 degrees C) as judged from the clonogenic surviving fractions from established human colon cancer cell lines. Our in vitro and in vivo results suggest that whole body hyperthermia combined with 5-FU is an active combination to develop further in the treatment of colorectal carcinomas.