Protection of normal tissue from the cytotoxic effects of chemotherapy and radiation by amifostine: clinical experiences

Abstract

The clinical trials described in this review indicate that amifostine protects normal tissues from the toxicities of various antitumour regimens. In a controlled trial, pretreatment with amifostine reduced the frequency of cyclophosphamide-induced neutropenia. Comparisons of the effects of cisplatin with and without pretreatment with amifostine indicated that patients pretreated with amifostine had fewer nephrotoxic and neurotoxic effects and tolerated higher doses of cisplatin before the onset of neurotoxic effects. In a randomised trial, patients who received amifostine prior to treatment with cyclophosphamide and cisplatin discontinued chemotherapy because of haemato, nephro- or ototoxicity less frequently than patients treated with cyclophosphamide and cisplatin alone. Tumour response rates and survival were comparable in both groups indicating that amifostine selectively protects only normal tissues. A regimen of amifostine plus cisplatin and vinblastine followed by amifostine plus radiation in patients with non-small cell lung cancer revealed a 73% response to treatment. Other studies showed that amifostine protected against late radiation toxicity to pelvic organs without interfering with the antitumour effect of radiotherapy, and decreased the haematological and mucosal toxicity of combined treatment with cisplatin and radiation therapy.