Cisplatin-associated anemia: an erythropoietin deficiency syndrome.
Cisplatin-based therapy results in a cumulative anemia that is disproportionate to the effects on other blood cells. The severity of this treatment-induced anemia and the resultant transfusion requirement in cancer patients correlate with cisplatin-induced renal tubular dysfunction. Observed/expected serum erythropoietin (EPO) ratios decline with progressive cisplatin therapy and are proportionate to the degree of renal dysfunction. Recovery from anemia and of observed/expected serum EPO ratios in patients occurs after cessation of cisplatin therapy, along with restoration of renal tubular function. Creatinine clearance, however, remains permanently depressed. Cisplatin-treated rats develop progressive renal dysfunction and anemia that persists for many weeks, without effects on white blood cell counts. The anemia is also associated with a lack of expected EPO and reticulocyte response. With EPO administration, cisplatin-treated rats exhibit a greater reticulocyte response and hematocrit increment then non-cisplatin-treated rats given EPO, indicating minimal erythroid precursor cell damage from cisplatin. These results indicate the primary etiology of cisplatin-associated anemia is a transient, but persisting EPO deficiency state resulting from cisplatin-induced renal tubular damage, which can be prevented or treated by hormone (EPO) replacement.
Wood
P A
PA
Stratton Veterans Affairs Medical Center, Albany, New York 12208, USA.
Hrushesky
W J
WJ
D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced*; D000818:Animals; D001772:Blood Cell Count; D001853:Bone Marrow / Q000187:drug effects; D002945:Cisplatin / Q000009:adverse effects* / Q000633:toxicity; D003404:Creatinine / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000009:adverse effects; D004921:Erythropoietin / Q000097:blood / Q000172:deficiency*; D005260:Female; D005500:Follow-Up Studies; D006400:Hematocrit; D006801:Humans; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D008274:Magnesium / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010051:Ovarian Neoplasms / Q000628:therapy; D010659:Phenylhydrazines / Q000494:pharmacology; D051381:Rats; D013577:Syndrome; D001749:Urinary Bladder Neoplasms / Q000628:therapy
D010659:Phenylhydrazines; D004921:Erythropoietin; D004317:Doxorubicin; D003404:Creatinine; C006384:N(1)-acetylphenylhydrazine; D008274:Magnesium; D002945:Cisplatin