Amifostine - An update on its clinical status as a cytoprotectant in patients with cancer receiving chemotherapy or radiotherapy and its potential therapeutic application in myelodysplastic syndrome

Amifostine (WR-2721) is a cytoprotective agent that protects a broad range of normal tissues from the toxic effects of chemotherapy and radiotherapy w ithout attenuating tumour response. This selective protection is due to the greater conversion and uptake of the active metabolite. WR-1065, in normal versus neoplastic tissues. In a pivotal phase III trial, 242 patients with advanced ovarian cancer wer e randomised to receive treatment with cisplatin 100 mg/m(2) and cyclophosp hamide 1000 mg/m(2) every 3 weeks with or without pretreatment with intrave nous amifostine 910 mg/m(2). Over 6 cycles of therapy, amifostine significa ntly reduced haematological. renal and neurological toxicities: treatment d elays, treatment discontinuation and days in hospital related to these adve rse events were also significantly reduced in patients receiving amifostine versus patients receiving chemotherapy alone. In another randomised phase III trial in 303 patients with head and neck ca ncer undergoing irradiation therapy (total dose 50 to 70Gy), pretreatment w ith intravenous amifostine 200 mg/m(2) significantly reduced the incidence of acute and late grade greater than or equal to2 xerostomia, However, muco sitis was not significantly reduced in amifostine recipients compared with patients receiving radiotherapy alone, although this has been shown in smal ler randomised trials. Amifostine (340 mg/m(2)) also provided significant protection against pneum onitis and oesophagitis in patients with lung cancer receiving thoracic irr adiation in a preliminary report from a phase III trial(n = 144). Other stu dies have demonstrated protective effects of amifostine in other tumour typ es and other chemotherapy, radiation and radiochemotherapy regimens; howeve r, evidence is still limited in these indications, No evidence of tumour pr otection by amifostine has been demonstrated in any clinical trials. Amifostine has also been shown to stimulate haematopoietic stem cells and h as been investigated as a therapy for patients with myelodysplastic syndrom e in number of small preliminary studies.