Antitumour efficacy of two paclitaxel formulations for hyperthermic intraperitoneal chemotherapy (HIPEC) in an in vivo rat model.

PURPOSE: To evaluate the tumour growth delay of a peritoneal carcinomatosis (PC) of colorectal origin after intraperitoneal chemotherapy with paclitaxel/randomly-methylated-ß-cyclodextrin (Pac/RAME-ß-CD) versus Taxol® at normo- and hyperthermic conditions in rats. METHODS: Hyperthermic intraperitoneal chemotherapy (HIPEC) was performed 7 days post implantation of the tumour with both formulations at a Pac concentration of 0.24 mg/ml. Tumour evaluation was performed via positron emission tomography (PET) and magnetic resonance imaging (MRI) imaging, measuring tumour activity and tumour volume, respectively. Scans were taken at 2 and 7 days post treatment. RESULTS: PET and MRI data showed a significant reduction in tumour activity and tumour volume for rats treated with Pac/RAME-ß-CD (at normo- and hyperthermic conditions), compared to the control group. Treatment with Taxol® did not result in a significant reduction of tumour activity and tumour volume. No significant differences between the normo- and hyperthermic conditions were observed for both formulations, indicating that hyperthermia and paclitaxel were not synergistic despite the direct cytotoxic effect of hyperthermia. CONCLUSION: Monitoring tumour growth via PET and MRI indicated that Pac/RAME-ß-CD inclusion complexes had a significantly higher efficacy compared to Taxol® in a rat model for peritoneal carcinomatosis.