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 chemotherapy can be shown to enhance neoplastic cell killing without a concomitant rise in bone marrow toxicity, nephrotoxicity can become treatment-limiting. This study compares the kidney toxicity to the kidney of ifosfamide, carboplatin 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 chemotherapy treatment there was a significant increase in urinary protein excretion and a reduction of the glomerular filtration rate. These effects were more pronounced if WBH was added. The use of immunoluminometric assays revealed a predominance of low-molecular-mass proteins. This increase in protein excretion 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 glomerular damage, which is enhanced by WBH. In terms of long-term nephrotoxicity e-WBH was more nephrotoxic than r-WBH. This finding is consistent with our clinical observations.
Gerke
P
P
Department of Internal Medicine I, Medical University of Lübeck, Germany. gerke@hotmail.com
Filejski
W
W
Robins
H I
HI
Wiedemann
G J
GJ
Steinhoff
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000378:metabolism; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D016190:Carboplatin / Q000009:adverse effects*; D017322:Clinical Trials, Phase II as Topic; D003404:Creatinine / Q000097:blood; D005047:Etoposide / Q000009:adverse effects*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006023:Glycoproteins / Q000652:urine; D006801:Humans; D006979:Hyperthermia, Induced / Q000009:adverse effects / Q000379:methods; D007069:Ifosfamide / Q000009:adverse effects*; D007074:Immunoglobulin G / Q000652:urine; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy / Q000628:therapy*; D014360:Trypsin Inhibitor, Kunitz Soybean
D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D006023:Glycoproteins; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; C109148:SPINT2 protein, human; D005047:Etoposide; D014360:Trypsin Inhibitor, Kunitz Soybean; D003404:Creatinine; D016190:Carboplatin; D007069:Ifosfamide