Amifostine protects against early but not late toxic effects of doxorubicin in infant rats

The improved prognosis and increased expected lifetime among longterm survi vors of childhood malignancies have made these patients especially sensitiv e to the late toxicity of cancer therapy and prone to secondary malignancie s. Recently, new strategies aiming to protect against cancer treatment toxi city have been developed, including the drug amifostine (Ethyol), which is suggested to protect normal tissues from the toxic effects of radiation and cytotoxic agents. In the present study, the possible protective effect of amifostine against toxicity induced by a single injection of doxorubicin (3 mg/kg) in immature rats was evaluated. Specifically, we evaluated the prot ection against long-term toxicity and the effects of amifostine on growing immature tissues. Amifostine (50-200 mg/kg) given 15 min before doxorubicin had a significant protective effect against doxorubicin-induced early alop ecia in young rats. Significant protection against cataract formation was o btained by the use of low-dose amifostine (50 mg/kg). However, amifostine d id not protect young rats against the late toxic effect of doxoubicin on li near growth, body weight, plasma leptin levels, and heart or testicular tis sue. Worrisome, and in contrast to earlier studies in adult rats, an increa sed doxorubicin toxicity actually was observed and mortality was increased when the higher doses of amifostine (100-200 mg/kg) were used. The present results suggest that more data from growing immature animal models are need ed to analyze the safety of amifostine treatment and its mechanisms of acti on before wider clinical use of this drug in pediatric cancer patients is r ecommended.