Hyperthermia enhances the response of paclitaxel and radiation in a mouse adenocarcinoma

Purpose: The aim of our study was to investigate if the efficacy of paclitaxel and paclitaxel radiation treatments in vivo could be enhanced by hyperthermia, Materials and Methods: Paclitaxel was administered i.p. in doses from 30 to 60 mg/kg b.w. to (C3D2F1) mice bearing spontaneous mammary carcinoma, Local hyperthermia (41 degrees, 42 degrees, 43 degrees C) was carried out by immersing tumor-bearing legs in a water bath for 1 h, Single X-ray treatments from 10 to 90 Gy were performed, Tumor growth delay (TGD) or tumor control dose (TCD50, radiation dose needed to induce local tumor control in 50% of irradiated animals) were the endpoints, Results: A significant increase of dose-dependent growth delay was observed in paclitaxel and 43 degrees C hyperthermia combined treatments, and a superadditive effect was seen with paclitaxel 45 mg/kg, Combined treatments with hyperthermia at 41 degrees and 42 degrees C were less effective, Administration of paclitaxel 24 h, 4 h, and 15 min before or 15 min and 4 h after hyperthermic treatments produced similar results (TGDs varying from 22.1 to 17 days), and administering paclitaxel 48 h before or 24 h after hyperthermic treatments decreased TGDs (about 10 days), Trimodality treatment (paclitaxel 45 mg/kg, hyperthermia, and X-ray), with a TCD50 of 14.1 Gy, in respect to the TCD50 of 53.1 obtained with X-ray alone, was the most effective. Conclusions: Hyperthermia enhanced the effectiveness of paclitaxel in all the tested protocols. Our results show a superadditive effect of paclitaxel 45 mg/kg combined with a hyperthermic treatment of I h at 43 degrees C, Trimodality treatment, evaluated in terms of percentage of cures, shows a very high enhancement ratio, (C) 1999 Elsevier Science Inc.