A randomized trial comparing the nephrotoxicity of cisplatin/ifosfamide-based combination chemotherapy with or without amifostine in patients with solid tumors

This study evaluates the degree of kidney damage during cisplatin/ifosfamid e-based combination chemotherapy and its possible prevention by amifostine. Thirty-one patients with solid tumors stratified according to pretreatment were randomized to receive VIP- or TIP-chemotherapy with or without amifos tine (910 mg/m(2)) given as a short infusion prior to cisplatin. Chemothera py consisted of cisplatin (50 mg/m(2)), ifosfamide (4 g/m(2)) and either et oposide (500 mg/m(2)) (= VIP) or paclitaxel (175 mg/m(2)) (= TIP) repeated at 3 weekly intervals. For all patients the glomerular filtration rate (GFR ) measured by creatinine-clearance, serum creatinine, electrolytes and diff erential urinary protein/enzyme excretion were determined prior to, during and after each cycle. A total of 62 cycles of chemotherapy were evaluable. In the amifostine-group GFR was fully maintained after application of two c ycles of chemotherapy, whereas in the control group a > 30%-reduction of me dian GFR (108 to 80 ml/min) was observed (p < 0.001). Patients receiving am ifostine had a lower degree of high molecular weight proteins excretion ind icating less glomerular damage. In both groups significant increases of tub ular marker profiles peaking at day 3 after chemotherapy were observed with a nearly complete reversibility of these changes prior to the next chemoth erapy cycle. The number of patients with low magnesium serum levels during treatment was 17% after amifostine application versus 69% in control patien ts. The results seem to indicate that treatment with amifostine can preserv e GFR after application of two cisplatin/ifosfamide-based chemotherapy cycl es. This may be advantageous if repetitive cycles of chemotherapy or subseq uent administration of high dose chemotherapy is planned.