A randomized trial of amifostine in patients with high-dose VIC chemotherapy plus autologous blood stem cell transplanation

This pilot study evaluates the degree of side effects during high-dose chem otherapy (HD-VIC) plus autologous bone marrow transplant (HDCT) and its pos sible prevention by the cytoprotective thiol-derivate amifostine. Additiona lly, the in-patient medical costs of both treatment arms were compared. 40 patients with solid tumours were randomized to receive HD-VIC chemotherapy with or without amifostine (910 mg/m(2) at day 1-3) given as a short infusi on prior to carboplatin and ifosfamide. Patients were stratified according to pretreatment. HDCT consisted of an 18 h infusion of carboplatin (500 mg/ m(2)d over 18 h), ifosfamide (4 g/m(2)/d over 4 h) and etoposide (500 mg/m( 2)/d) all given for 3 consecutive days. All patients received prophylactic application of G-CSF (5 mug kg(-1) subcutaneously) to ameliorate neutropeni a after treatment. Patients were monitored for nephrotoxicity, gastrointest inal side effects, haematopoietic recovery, as well as frequency of fever a nd infections. The median fall of the glomerular filtration rate (GFR) was 10% from baseline in the amifostine group (105 to 95 ml min(-1)) and 37% in the control patient group (107 to 67 ml min(-1)) (P< 0.01). Amifostine-tre ated patients revealed a less pronounced increase in albumine and low molec ular weight protein urinary excretion. Stomatitis grade III/IV occurred in 25% without versus 0% of patients with amifostine (P = 0.01). Acute nausea/ vomiting was frequently observed immediately during or after the applicatio n of amifostine despite intensive antiemetic prophylaxis consisting of 5-HT 3-reoeptor antagonists/dexamethasone/trifluorpromazine. However, delayed em esis occurred more often in the control patients. Engraftment of neutrophil (> 500 mul(-1)), and thrombocytes (> 25 000 mul(-1)),were observed at days 9 versus 10 and 10 versus 12, respectively, both slightly in favour of the amifostine arm. In addition, a lower number of days with fever and a short ened duration of hospital stay were observed in the amifostine arm. The red uction of acute toxicity observed in the amifostine arm resulted in 30% sav ings in costs for supportive care (Euro 4396 Versus Euro 3153 per patient). Taking into account the drug costs of amifostine, calculation of in-patien t treatment costs from the start of chemotherapy to discharge revealed addi tional costs of Euro 540 per patient in the amifostine arm. This randomized pilot study indicates that both organ and haematotoxicity of HD-VIC chemot herapy can be ameliorated by the use of amifostine. Additionally, a nearly complete preservation of GFR was observed in amifostine-treated patients wh ich may be advantageous if repetitive cycles of HDCT are planned. Larger ra ndomized trials evaluating amifostine cytoprotection during high-dose chemo therapy are warranted. (C) 2001 cancer Research Campaign.