2002 CTOS Annual Meeting Posters — Radiation Oncology

NOVEL RADIOPROTECTANT DRUGS OTHER THAN AMIFOSTINE FOR SPARING RADIATION-INDUCED DAMAGE TO THE PHYSIS
[Abstract ID: 38]

Category: Radiation Oncology

Authors: Timothy A. Damron¹, Joseph A. Spadaro¹, Jason Horton¹, Bryan Margulies¹, Judy Strauss¹, Cornelia N. Farnum²

Author Institutions: ¹SUNY Upstate Medical University at Syracuse, New York, United States; ²Cornell University College of Veterinary Medicine, New York, United States

Presenter: Timothy A. Damron
tdamron@twcny.rr.com

Correspondent: Timothy A. Damron
tdamron@twcny.rr.com
Syracuse New York United States 13202
Ph: 315-464-4472
Fax: 315-464-4664

Objectives: Amifostine, a selective free-radical scavenger, is the only previously documented drug to achieve radioprotection of the growth plate, but its effect is incomplete. The aim of this pilot is to determine if any of four novel radioprotectant drugs other than amifostine can individually preserve the integrity of, or minimize damage to, physeal longitudinal growth during single radiation dose exposure in an animal model.

Methods: Eighty-four weanling male Sprague-Dawley rats were randomized into 16 groups of 4-6 animals. All groups received single 17.5 Gy radiation exposure to the right knee with the left serving as control. Groups IA-C received pentoxifylline 50, 200, and 300 mg/kg. Groups IIA-B received selenium selenite 1.5 and 5 mg/kg. Groups IIIA-E received IL-1b 5, 15, 50, 125, and 500 mcg/kg. Groups IVA-E received misoprostol 0.1, 0.5, 1, 0, and 5 mg/kg. Group V received irradiation alone. At 6 weeks femoral and tibial lengths were measured and limb length percentage differences calculated between irradiated and unirradiated limbs. ANOVA was employed with alpha 0.05.

Results: The radiation dose of 17.5 Gy caused a mean femoral length discrepancy of 21.1%. Pentoxifylline at the lowest dose reduced mean femoral limb discrepancy to 15.3% (p=0.0001). Higher doses were less effective. IL-1beta at 15 mcg/kg reduced femoral mean length discrepancy to 16.7% (p<0.0001). Selenium and misoprostol demonstrated dose-dependent effects, the highest dose for each resulting in 17.2% discrepancy (p<0.03).

Conclusions: At specific doses, each of the four tested drugs, administered prior to a single irradiation dose, significantly reduced limb length discrepancy in our animal model. The magnitude of the reduction remains less than previously demonstrated for amifostine. Combination studies are underway.