PROTECTION OF NORMAL TISSUE FROM THE CYTOTOXIC EFFECTS OF CHEMOTHERAPY AND RADIATION BY AMIFOSTINE - CLINICAL-EXPERIENCES

The clinical trials described in this review indicate that amifostine protects normal tissues from the toxicities of various antitumour regi mens. 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 ind icated 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 r eceived amifostine prior to treatment with cyclophosphamide and cispla tin discontinued chemotherapy because of haemato, nephro- or ototoxici ty less frequently than patients treated with cyclophosphamide and cis platin alone. Tumour response rates and survival were comparable in bo th groups indicating that amifostine selectively protects only normal tissues. A regimen of amifostine plus cisplatin and vinblastine follow ed by amifostine plus radiation in patients with non-small cell lung c ancer 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 de creased the haematological and mucosal toxicity of combined treatment with cisplatin and radiation therapy.