Nephrotoxicity of ifosfamide, carboplatin and etoposide (ICE) alone or combined with extracorporeal or radiant-heat-induced whole-body hyperthermia

Although whole-body hyperthermia combined with specific genotoxic chemother apy can be shown to enhance neoplastic cell killing without a concomitant r ise in bone marrow toxicity, nephrotoxicity can become treatment-limiting. This study compares the kidney toxicity to the kidney of ifosfamide, carbop latin and etoposide (ICE) chemotherapy alone, and ICE chemotherapy combined with either extracorporeal (e-WBH) or radiant-heat-induced hyperthermia (r -WBH) in 43 patients with refractory sarcoma. Within 3 days of ICE chemothe rapy treatment there was a significant increase in urinary protein excretio n and a reduction of the glomerular filtration rate. These effects were mor e pronounced if WBH was added. The use of immunoluminometric assays reveale d a predominance of low-molecular-mass proteins. This increase in protein e xcretion persisted in the e-WBH-treated group, whereas it vanished within 3 weeks in both the group treated with ICE alone and that treated with r-WBH . Our findings suggest that ICE chemotherapy causes transient tubular and g lomerular damage, which is enhanced by WBH. In terms of long-term nephrotox icity e-WBH was more nephrotoxic than r-WBH. This finding is consistent wit h our clinical observations.