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

ABSTRACT

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 Gy 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. Six 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.