Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1998 Sep;78(6):752–756. doi: 10.1038/bjc.1998.572

Enhanced radiosensitivity in experimental tumours following erythropoietin treatment of chemotherapy-induced anaemia.

O Thews 1, R Koenig 1, D K Kelleher 1, J Kutzner 1, P Vaupel 1
PMCID: PMC2062974  PMID: 9743294

Abstract

The radiosensitivity of solid tumours in anaemic rats treated with recombinant human erythropoietin (rhEPO, epoetin beta) was studied. Anaemia was induced by a single dose of carboplatin (45 mg kg(-1) i.v.), resulting in a reduction in the haemoglobin concentration by 30%. In a second group, the development of anaemia was prevented by rhEPO (1000 IU kg(-1)) administered s.c. three times per week starting 6 days before the carboplatin application. Three days after carboplatin treatment, DS-sarcomas were implanted subcutaneously onto the hind foot dorsum. Neither carboplatin nor rhEPO treatment influenced tumour growth rate. Five days after implantation, tumours were irradiated with a single non-curative dose (10 Gy), resulting in a growth delay with a subsequent regrowth of the tumours. In the rhEPO-treated group, the growth delay lasted significantly longer (9.5 days vs. 4.5 days) and the regrowth was slower (6.0 days vs. 4.1 days) compared with the anaemic group. These data suggest that the correction of chemotherapy-induced anaemia by rhEPO (epoetin beta) treatment increases tumour radiosensitivity, presumably as a result of an improved oxygen supply to tumour tissue.

Full text

PDF
752

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bush R. S., Jenkin R. D., Allt W. E., Beale F. A., Bean H., Dembo A. J., Pringle J. F. Definitive evidence for hypoxic cells influencing cure in cancer therapy. Br J Cancer Suppl. 1978 Jun;3:302–306. [PMC free article] [PubMed] [Google Scholar]
  2. Busse M., Vaupel P. W. The role of tumor volume in 'reoxygenation' upon cyclophosphamide treatment. Acta Oncol. 1995;34(3):405–408. doi: 10.3109/02841869509093998. [DOI] [PubMed] [Google Scholar]
  3. Hewitt H. B., Blake E. R. Effect of induced host anaemia on the viability and radiosensitivity of murine malignant cells in vivo. Br J Cancer. 1971 Jun;25(2):323–336. doi: 10.1038/bjc.1971.42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hill R. P., Bush R. S., Yeung P. The effect of anaemia on the fraction of hypoxic cells in an experimental tumour. Br J Radiol. 1971 Apr;44(520):299–304. doi: 10.1259/0007-1285-44-520-299. [DOI] [PubMed] [Google Scholar]
  5. Hirst D. G., Hazlehurst J. L., Brown J. M. The effect of alterations in haematocrit on tumour sensitivity to X-rays. Int J Radiat Biol Relat Stud Phys Chem Med. 1984 Oct;46(4):345–354. doi: 10.1080/09553008414551521. [DOI] [PubMed] [Google Scholar]
  6. Joiner B., Hirst V. K., McKeown S. R., McAleer J. J., Hirst D. G. The effect of recombinant human erythropoietin treatment on tumour radiosensitivity and cancer-associated anaemia in the mouse. Br J Cancer. 1993 Oct;68(4):720–726. doi: 10.1038/bjc.1993.417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kelleher D. K., Matthiensen U., Thews O., Vaupel P. Tumor oxygenation in anemic rats: effects of erythropoietin treatment versus red blood cell transfusion. Acta Oncol. 1995;34(3):379–384. doi: 10.3109/02841869509093993. [DOI] [PubMed] [Google Scholar]
  8. Lavey R. S., Dempsey W. H. Erythropoietin increases hemoglobin in cancer patients during radiation therapy. Int J Radiat Oncol Biol Phys. 1993 Dec 1;27(5):1147–1152. doi: 10.1016/0360-3016(93)90536-5. [DOI] [PubMed] [Google Scholar]
  9. Markman M., Reichman B., Hakes T., Rubin S., Jones W., Lewis J. L., Jr, Barakat R., Curtin J., Almadrones L., Hoskins W. The use of recombinant human erythropoietin to prevent carboplatin-induced anemia. Gynecol Oncol. 1993 May;49(2):172–176. doi: 10.1006/gyno.1993.1102. [DOI] [PubMed] [Google Scholar]
  10. McCormack M., Nias A. H., Smith E. Chronic anaemia, hyperbaric oxygen and tumour radiosensitivity. Br J Radiol. 1990 Oct;63(754):752–759. doi: 10.1259/0007-1285-63-754-752. [DOI] [PubMed] [Google Scholar]
  11. Ohno S., Strebel F. R., Stephens L. C., Siddik Z. H., Baba H., Makino M., Khokhar A. R., Bull J. M. Haematological toxicity of carboplatin and cisplatin combined with whole body hyperthermia in rats. Br J Cancer. 1993 Sep;68(3):469–474. doi: 10.1038/bjc.1993.372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Reece P. A., Bishop J. F., Olver I. N., Stafford I., Hillcoat B. L., Morstyn G. Pharmacokinetics of unchanged carboplatin (CBDCA) in patients with small cell lung carcinoma. Cancer Chemother Pharmacol. 1987;19(4):326–330. doi: 10.1007/BF00261482. [DOI] [PubMed] [Google Scholar]
  13. Rojas A., Stewart F. A., Smith K. A., Soranson J. A., Randhawa V. S., Stratford M. R., Denekamp J. Effect of anemia on tumor radiosensitivity under normo and hyperbaric conditions. Int J Radiat Oncol Biol Phys. 1987 Nov;13(11):1681–1689. doi: 10.1016/0360-3016(87)90165-9. [DOI] [PubMed] [Google Scholar]
  14. Siddik Z. H., Boxall F. E., Harrap K. R. Haematological toxicity of carboplatin in rats. Br J Cancer. 1987 Apr;55(4):375–379. doi: 10.1038/bjc.1987.75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Spivak J. L. Recombinant human erythropoietin and the anemia of cancer. Blood. 1994 Aug 15;84(4):997–1004. [PubMed] [Google Scholar]
  16. Tannock I. F., Steel G. G. Tumor growth and cell kinetics in chronically hypoxic animals. J Natl Cancer Inst. 1970 Jul;45(1):123–133. [PubMed] [Google Scholar]
  17. Vaupel P., Kallinowski F., Okunieff P. Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res. 1989 Dec 1;49(23):6449–6465. [PubMed] [Google Scholar]
  18. Vijayakumar S., Roach M., 3rd, Wara W., Chan S. K., Ewing C., Rubin S., Sutton H., Halpern H., Awan A., Houghton A. Effect of subcutaneous recombinant human erythropoietin in cancer patients receiving radiotherapy: preliminary results of a randomized, open-labeled, phase II trial. Int J Radiat Oncol Biol Phys. 1993 Jul 15;26(4):721–729. doi: 10.1016/0360-3016(93)90299-b. [DOI] [PubMed] [Google Scholar]
  19. de Campos E., Radford J., Steward W., Milroy R., Dougal M., Swindell R., Testa N., Thatcher N. Clinical and in vitro effects of recombinant human erythropoietin in patients receiving intensive chemotherapy for small-cell lung cancer. J Clin Oncol. 1995 Jul;13(7):1623–1631. doi: 10.1200/JCO.1995.13.7.1623. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES