Nephrotoxicity after high-dose carboplatin, etoposide and ifosfamide in germ-cell tumors: incidence and implications for hematologic recovery and clinical outcome

Abstract

High-dose carboplatin, etoposide and ifosfamide (CEI) is an active chemotherapy regimen (HDCT) in solid tumors and lymphomas. In patients with previous exposure to cisplatin, its nephrotoxicity is dose-limiting. To determine the implications of nephrotoxicity on hematological recovery and clinical outcome, we analyzed 150 consecutive patients with germ cell tumors treated between August 1989 and September 1995 with carboplatin 1500-2000 mg/m2, etoposide 1200-2400 mg/m2, and ifosfamide 0-10 g/m2 followed by either BM or PBPC rescue. Five patients died (3%), three in the context of severe renal toxicity and early multiorgan failure. Overall, acute nephrotoxicity occurred in 43/150 (29%) patients, particularly at doses of carboplatin >1500 mg/m2. Hemodialysis was required in 12/150 (8%) patients, but could be discontinued until discharge in all except two survivors. Nephrotoxicity did not delay hematologic recovery when adjusted for the use of PBPC and hematopoietic growth factors by multivariate analysis, but resulted in higher transfusion requirements, more overall toxicities and a longer hospital stay. There were no differences in the response rates or survival in patients with or without nephrotoxicity. Acute nephrotoxicity is a frequent and clinically relevant complication of CEI in germ cell tumors. The acute side-effects from CEI are reversible in the majority of patients.