Erythropoietin restores the anemia-induced reduction in cyclophosphamide cytotoxicity in rat tumors.
The aim of this study was to examine the impact of anemia prevention by recombinant human erythropoietin (rHuEPO) treatment on the cytotoxicity of cyclophosphamide in solid experimental tumors. Anemia was induced using a single dose of carboplatin (50 mg/kg i.v.) resulting in a long-lasting reduction (30%) of the hemoglobin concentration. In a second group, the development of anemia was prevented by rHuEPO (1000 IU/kg) administered s.c. three times/week starting 7 days before carboplatin application. Four days after carboplatin treatment, tumors (DS-sarcoma of the rat) were implanted s.c. onto the hind food dorsum. Neither carboplatin nor rHuEPO treatment influenced tumor growth rate per se. When tumors were treated with a single dose of cyclophosphamide (60 mg/kg i.p.) 5 days after implantation, a growth delay with a subsequent regrowth of the tumors was observed. In the anemia group, the growth delay was significantly shorter compared with nonanemic controls (13.3 days versus 8.6 days). In the group where anemia was prevented by rHuEPO treatment, growth delay was comparable with that of nonanemic controls (13.3 days). These results suggest that chemotherapy-induced anemia reduces cytotoxicity of cyclophosphamide in tumors, whereas correction of anemia by rHuEPO treatment (epoetin alpha) increases the sensitivity, probably as a result of an improved oxygen supply to tumor tissue.
Thews
O
O
Institute of Physiology and Pathophysiology, University of Mainz, Germany. OLTHEWS@mail.uni-mainz.de
Kelleher
D K
DK
Vaupel
P
P
D000740:Anemia / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D016190:Carboplatin / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D003520:Cyclophosphamide / Q000633:toxicity*; D004921:Erythropoietin / Q000494:pharmacology*; D008297:Male; D009368:Neoplasm Transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D012513:Sarcoma, Experimental / Q000188:drug therapy / Q000473:pathology
D018906:Antineoplastic Agents, Alkylating; D011994:Recombinant Proteins; D004921:Erythropoietin; D003520:Cyclophosphamide; D016190:Carboplatin