Phase I-II study of escalating doses of amifostine combined with high-dosecyclophosphamide

Purpose: To evaluate the feasibility and clinical effects of increasing dos es of amifostine administered four times in 1 day with high-dose (HD) cyclo phosphamide (CTX). Methods: A group of 16 patients with a diagnosis of lymp homa were treated with HD-CTX given at a total dose of 7 g/m(2) subdivided into four doses, each preceded by increasing doses of amifostine. A group o f 12 lymphoma patients previously treated with the same HD-CTX regimen was used as historical controls. Results: The dose of amifostine was escalated in cohorts of three patients each from 4x570 mg/m(2) to 4x910 mg/m(2) witho ut severe toxic effects. Further patients were treated at the highest dose level. Side effects included a fall in blood pressure (always less than 20% of baseline value), asymptomatic hypocalcemia (from a median value of 2.4 to 1.7 mmol/l) and a decrease in creatinine clearance (from a median value of 102 to 85 ml/min). The parameters of hematotoxicity for patients treated in the study were not significantly different from those of the historical control patients. Conclusions: Amifostine call be given safely at a dose o f 910 mg/m(2) four times in 1 day in combination with HDCTX. With this sche dule amifostine did not show a myeloprotective effect.