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

Anna Cividalli D.sc, Giorgio Cruciani, Esther Livdi, Patrizio Pasqualetti, Donatella Tirindelli Danesi

Research output: Contribution to journalArticle

Abstract

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°, 42°, 43°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°C hyperthermia combined treatments, and a superadditive effect was seen with paclitaxel 45 mg/kg. Combined treatments with hyperthermia at 41°and 42°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 1 h at 43°C. Trimodality treatment, evaluated in terms of percentage of cures, shows a very high enhancement ratio.

Original languageEnglish
Pages (from-to)407-412
Number of pages6
JournalInternational Journal of Radiation Oncology Biology Physics
Volume44
Issue number2
DOIs
Publication statusPublished - May 1999

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Keywords

  • Hyperthermia
  • Mammary carcinoma
  • Mouse
  • Paclitaxel
  • Radiation

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

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