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

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.

• Authors: Wim Bouquet, Steven Deleye, Steven Staelens, Lieselotte De Smet, Nancy Van Damme, Isabelle Debergh, Wim P Ceelen, Filip De Vos, Jean Paul Remon, Chris Vervaet
• Journal: Pharmaceutical research (Pharm Res) Vol. 28 Issue 7 Pg. 1653-60 (Jul 2011) ISSN: 1573-904X [Electronic] United States
• PMID: 21424162 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• beta-Cyclodextrins
• Paclitaxel

Topics

• 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, prevention & control)
• Positron-Emission Tomography
• Rats
• Time Factors
• Tumor Burden
• beta-Cyclodextrins (therapeutic use)