title: Human recombinant erythropoietin significantly improves tumor oxygenation independent of its effects on hemoglobin.
abstract: Tumor oxygenation is known to be an important predictive/prognostic marker in a variety of tumors, including cervix, head/neck, sarcoma, non-small cell of the lung, and breast. Tumor oxygenation is influenced by many interactions, including oxygen delivery (angiogenesis, permeability, and HgB) and consumption (metabolic and growth rates). This study randomized 30 nonanemic, female Fischer 344 rats into three treatment arms to examine the effects of recombinant human erythropoietin (EPO) on R3230 rodent mammary carcinoma oxygenation. The three treatment arms were: (a) placebo; (b) EPO after tumor implantation (2000 units/kg/SQdose, M/W/F for six doses); and (c) EPO before tumor implantation (2000 units/kg/SQdose, M/W/F for six doses). Tumors were implanted in the hindflank, and in vivo oxygenation was measured at day 22 after implantation using the Oxylite system (Oxford Optronix, Oxford, England). An average of 180 measurements/animal were performed. On day 22, median tumor volume was 399 mm(3) (range: 65-950 mm(3)), and no differences in tumor volume were seen between treatment arms. Mean hematocrit was equal between arms at therapy initiation but were significantly higher for both arms receiving EPO at day 22 (placebo versus Arm B versus Arm C; Wilcoxon P = 0.052). EPO-treated tumors had significantly less hypoxic measurements when compared with either the placebo or those receiving EPO before implantation. These data confirm that tumor oxygenation in nonanemic individuals may be improved through the administration of EPO, and this improvement appears to be independent of HgB effects.
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke University Comprehensive Cancer Center, Erwin Road, Durham, NC 27710, USA. black034@mc.duke.edu
authors.forename: Kimberly L
authors.initials: KL
authors.lastname: Blackwell
authors.forename: John P
authors.initials: JP
authors.lastname: Kirkpatrick
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Snyder
authors.forename: Gloria
authors.initials: G
authors.lastname: Broadwater
authors.forename: Francis
authors.initials: F
authors.lastname: Farrell
authors.forename: Linda
authors.initials: L
authors.lastname: Jolliffe
authors.forename: David M
authors.initials: DM
authors.lastname: Brizel
authors.forename: Mark W
authors.initials: MW
authors.lastname: Dewhirst
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000188:drug therapy*; D000818:Animals; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000097:blood* / Q000188:drug therapy*; D009368:Neoplasm Transplantation; D010100:Oxygen / Q000097:blood* / Q000378:metabolism; D010313:Partial Pressure; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins
chemical_list: D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D010100:Oxygen