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

Author(s): Hartmann JT, Fels LM, Knop S, Stolt H, Kanz L, Bokemeyer C

Affiliation(s): Department of Hematology and Oncology, UKT-Medical Center II, Eberhard-Karls-University of Tubingen, Germany. joerg.hartmann@med.uni-tuebingen.de

Publication date & source: 2000-08, Invest New Drugs., 18(3):281-9.

Publication type: Clinical Trial; Randomized Controlled Trial

This study evaluates the degree of kidney damage during cisplatin/ifosfamide-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 amifostine (910 mg/m2) given as a short infusion prior to cisplatin. Chemotherapy consisted of cisplatin (50 mg/m2), ifosfamide (4 g/m2) and either etoposide (500 mg/m2) (= VIP) or paclitaxel (175 mg/m2) (= TIP) repeated at 3 weekly intervals. For all patients the glomerular filtration rate (GFR) measured by creatinine-clearance, serum creatinine, electrolytes and differential 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 cycles of chemotherapy, whereas in the control group a > 30%-reduction of median GFR (108 to 80 ml/min) was observed (p < 0.001). Patients receiving amifostine had a lower degree of high molecular weight proteins excretion indicating less glomerular damage. In both groups significant increases of tubular marker profiles peaking at day 3 after chemotherapy were observed with a nearly complete reversibility of these changes prior to the next chemotherapy cycle. The number of patients with low magnesium serum levels during treatment was 17% after amifostine application versus 69% in control patients. The results seem to indicate that treatment with amifostine can preserve GFR after application of two cisplatin/ifosfamide-based chemotherapy cycles. This may be advantageous if repetitive cycles of chemotherapy or subsequent administration of high dose chemotherapy is planned.