title: A randomized trial comparing the nephrotoxicity of cisplatin/ifosfamide-based combination chemotherapy with or without amifostine in patients with solid tumors.
abstract: 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.
authors.affiliation: Department of Hematology and Oncology, UKT-Medical Center II, Eberhard-Karls-University of Tübingen, Germany. joerg.hartmann@med.uni-tuebingen.de
authors.forename: J T
authors.initials: JT
authors.lastname: Hartmann
authors.forename: L M
authors.initials: LM
authors.lastname: Fels
authors.forename: S
authors.initials: S
authors.lastname: Knop
authors.forename: H
authors.initials: H
authors.lastname: Stolt
authors.forename: L
authors.initials: L
authors.lastname: Kanz
authors.forename: C
authors.initials: C
authors.lastname: Bokemeyer
mesh_terms: D000293:Adolescent; D000328:Adult; D004999:Amifostine / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D004999:Amifostine; D002945:Cisplatin; D007069:Ifosfamide