Yongbiao Li1, Abraham Owusu, Shirley Lehnert. 1. Department of Radiation Oncology, McGill University, Montreal General Hospital, 1650 Cedar Avenue, Montreal, Québec H3G 1A4, Canada.
Abstract
PURPOSE: To evaluate an intracranial polymer implant containing bromodeoxyuridine (BrdUrd) and N-(phosphonacetyl)-L-aspartic acid (PALA) in combination with external beam radiotherapy (EBRT) in the treatment of a rat glioma. METHODS AND MATERIALS: Combinations of the biomodulators 5-fluorouracil, methotrexate, or PALA with BrdUrd were evaluated as radiosensitizers in vitro by clonogenic assay. In in vivo experiments, BrdUrd and PALA were incorporated into a polyanhydride-based polymer, bis(p-carboxyphenoxy)propane sebacic acid, and implanted in the C6 rat glioma growing intracranially. The effectiveness of treatment was evaluated on the basis of survival. EBRT was given as 10-MV X-rays. RESULTS: In tissue culture experiments, C6 cells were refractory to radiosensitization by BrdUrd even when the thymidine analog was combined with a biomodulator intended to reduce de novo thymidine synthesis. The most effective compound in vitro was PALA. When PALA and BrdUrd in a polymer formulation were implanted intracranially and combined with 10-Gy EBRT, the treatment was highly effective, with 83% of treated rats surviving 180 days. CONCLUSION: Although the in vitro results were not encouraging, the combination of intratumoral BrdUrd and PAL with 10-Gy EBRT was highly effective in treating a rat glioma. These results indicate the clinical potential of combined and mixed modality treatments involving intratumoral sustained-release drug delivery.
PURPOSE: To evaluate an intracranial polymer implant containing bromodeoxyuridine (BrdUrd) and N-(phosphonacetyl)-L-aspartic acid (PALA) in combination with external beam radiotherapy (EBRT) in the treatment of a ratglioma. METHODS AND MATERIALS: Combinations of the biomodulators 5-fluorouracil, methotrexate, or PALA with BrdUrd were evaluated as radiosensitizers in vitro by clonogenic assay. In in vivo experiments, BrdUrd and PALA were incorporated into a polyanhydride-based polymer, bis(p-carboxyphenoxy)propanesebacic acid, and implanted in the C6 ratglioma growing intracranially. The effectiveness of treatment was evaluated on the basis of survival. EBRT was given as 10-MV X-rays. RESULTS: In tissue culture experiments, C6 cells were refractory to radiosensitization by BrdUrd even when the thymidine analog was combined with a biomodulator intended to reduce de novo thymidine synthesis. The most effective compound in vitro was PALA. When PALA and BrdUrd in a polymer formulation were implanted intracranially and combined with 10-Gy EBRT, the treatment was highly effective, with 83% of treated rats surviving 180 days. CONCLUSION: Although the in vitro results were not encouraging, the combination of intratumoral BrdUrd and PAL with 10-Gy EBRT was highly effective in treating a ratglioma. These results indicate the clinical potential of combined and mixed modality treatments involving intratumoral sustained-release drug delivery.
Authors: E Allard; F Hindre; C Passirani; L Lemaire; N Lepareur; N Noiret; P Menei; J-P Benoit Journal: Eur J Nucl Med Mol Imaging Date: 2008-05-09 Impact factor: 9.236