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

Pharm Res. 2011 Jul;28(7):1653-60. doi: 10.1007/s11095-011-0401-1. Epub 2011 Mar 18.

Abstract

Purpose: To evaluate the tumour growth delay of a peritoneal carcinomatosis (PC) of colorectal origin after intraperitoneal chemotherapy with paclitaxel/randomly-methylated-β-cyclodextrin (Pac/RAME-β-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-β-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-β-CD inclusion complexes had a significantly higher efficacy compared to Taxol® in a rat model for peritoneal carcinomatosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Cell Line, Tumor
  • Colorectal Neoplasms / drug therapy*
  • Combined Modality Therapy
  • Disease Models, Animal
  • Hyperthermia, Induced*
  • Injections, Intraperitoneal
  • Magnetic Resonance Imaging
  • Paclitaxel / therapeutic use*
  • Peritoneal Neoplasms / drug therapy*
  • Peritoneal Neoplasms / prevention & control
  • Positron-Emission Tomography
  • Rats
  • Time Factors
  • Tumor Burden
  • beta-Cyclodextrins / therapeutic use*

Substances

  • Antineoplastic Agents
  • beta-Cyclodextrins
  • Paclitaxel