Effects of recombinant human erythropoietin on the antitumor effect of cisplatin in SCID mice bearing human ovarian cancer: A possible oxygen effect

Purpose. Experiments were designed to evaluate the effect of an elevated he matocrit using recombinant human erythropoietin (Epo) on the antitumor resp onse of cisplatin on human ovarian cancer engrafted in mice. Methods. Forty female severe combined immunodeficient (SCID) mice with larg e human ovarian cancer xenografts implanted on the gonadal fat pad (GFP) an d 40 female SCID mice with small subcutaneous (sq) human ovarian cancer xen ografts were placed in one of four treatment groups. Group 1 (controls) rec eived phosphate-buffered saline injections. Group 2 (Epo group) received Ep o at 20 units three times per week. Group 3 (cisplatin group) received cisp latin at 5 mg/kg/week. Group 4 (Epo + cisplatin group) received Epo and cis platin as above. Cisplatin was administered on day 0 for mice bearing large GFP tumors and was injected on days 0 and +7 for mice bearing small sq tum ors. Epo injections were started on day -15 and continued until the complet ion of the experiment. Evaluations of the tumor growth, hematocrits, and pe rformance status were made. The experiments were repeated in 24 SCID mice b earing small sq tumor xenografts with similar results. Representative data were reported. Results. Among mice bearing large GFP tumors, a tumor growth delay was note d in the groups that received cisplatin with or without Epo compared to con trols (P < 0.05), However, significant tumor growth delay could not be reac hed for mice in the Epo + cisplatin group compared to the cisplatin group ( P = 0.07). Among mice bearing small sq tumors, a significant improvement in tumor regression was achieved in the Epo + cisplatin group compared to the cisplatin group (P < 0.05), No difference in tumor growth resulted in the Epo group compared to controls. Epo resulted in a 25-35% increase in the he matocrit in both the Epo group and the Epo + cisplatin group (P < 0.01). Mi ce in the control and in the Epo groups remained healthy. Mice treated with cisplatin developed objective signs of morbidity; however, performance sco res for mice in the Epo + cisplatin group remained lower than scores in the cisplatin group. Conclusions. The data demonstrate a cisplatin-sensitizing effect on human o varian cancer in SCID mice induced by the pretreatment elevation and mainte nance of the hematocrit using Epo, These findings are consistent with an ox ygen sensitization of cisplatin, Corroboration of these results may have si gnificant clinical implications for the treatment of solid tumor patients. (C) 1999 Academic Press.