Sparing of radiation-induced damage to the physis: Fractionation alone compared to amifostine pretreatment

Purpose: The purpose of this study was to determine the relative benefits of sparing longitudinal bone growth by fractionation alone compared to pretreatment with amifostine, a chemical that provides differential radioprotection of normal tissues. Methods and Materials: Twenty-four weanling 4-week-old male Sprague-Dawley rats were randomized into 2 overall treatment groups: fractionation alone (n = 12) and amifostine pretreatment (n = 12), The distal femur and proximal tibia in the right leg of each animal were exposed to a therapeutic X-irradiation dose (17.5 GS total in 3 or 5 fractions) with the contralateral left leg as control. In 12 of the animals, amifostine (100 mg/kg) was administered intraperitoneally 20 min before radiation exposure, Sh weeks later, growth was calculated based upon measurement of the bone lengths. Results: Fractionated radiation resulted in a mean percent overall limb growth loss of 21.1 +/- 7.0%. The addition of amifostine brought the mean percent overall limb growth loss to 16.3% +/- 4.6%, which showed a strong trend toward significance compared to fractionation alone (p = 0.061), The addition of radioprotection with amifostine to 5 fractions irradiation significantly reduced the femoral and overall percentage growth arrest and limb length discrepancy compared to 5 fractions alone. Conclusions: These results support further investigation of amifostine and other radioprotectants in combination with fractionation for use in growing children requiring radiotherapy to the extremity for malignant tumors, (C) 2000 Elsevier Science Inc.