Medical Oncology

, Volume 22, Issue 2, pp 161–168 | Cite as

Anemia in cervical cancer patients

Implications for iron supplementation therapy
  • Myrna Candelaria
  • Lucely Cetina
  • Alfonso Dueñas-GonzálezEmail author
Original Article


Iron deficiency and tumor bleeding are common causes of anemia in cervical cancer. Anemia has a negative prognostic influence, and its correction is thought to improve prognosis; therefore, most patients are treated with either transfusion and/or erythropoietin. At present little is known about the value of iron stores replenishment to increase hemoglobin levels in this setting. Untreated cervical cancer patients with a hemoglobin <12 g/dL were randomized to intramuscular iron or to transfusion. Iron dose was calculated according to [weight (kg) × (15 − actual Hb) × 2.4]+500 and administered by injections of 200 mg daily. In both arms, patients who did not achieve at least 10 g/dL hemoglobin before or during chemoradiation were transfused. Patients received standard pelvic radiation plus six weekly doses of cisplatin. Hematic counts were performed before starting chemoradiation and weekly thereafter. Fifteen patients were studied; six were assigned to iron and nine to transfusion. Mean basal hemoglobin levels were 9.9 and 9.5 g/dL respectively. Total iron, saturation index, binding capacity, and ferritin were within normal limits, although there was a high variability among the patients. The mean total dose of iron administered was 1229 mg. Two weeks after randomization, hemoglobin increased to 10.9 and 10.2 g/dL respectively. At wk 1 of treatment and thereafter, levels were higher in the iron arm, in whom the values were close or higher than 12 g/dL (p=0.03). The median number of units transfused were 0 in the iron group and 2 in the transfusion (p=0.02) arm. Parenteral iron seems to be effective to increase hemoglobin in cervical cancer patients.

Key Words

Anemia cervical cancer iron 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Duenas-Gonzalez A, Cetina L, Mariscal I, de la Garza J. Modern management of locally advanced cervical carcinoma. Cancer Treat Rev 2003;29:389–399.PubMedCrossRefGoogle Scholar
  2. 2.
    Black AK, Allen LH, Pelto GH, de Mata MP, Chavez A. Iron, vitamin B-12 and folate status in Mexico: associated factors in men and women and during pregnancy and lactation. J Nutr 1994;124:1179–1188.PubMedGoogle Scholar
  3. 3.
    Looker AC, Dallman PR, Carroll MD, Gunter EW, Johnson CL. Prevalence of iron deficiency in the United States. JAMA 1997;277:973–976.PubMedCrossRefGoogle Scholar
  4. 4.
    Evans JC, Bergsjø P. Influence of anemia on the results of radiation therapy in carcinoma of the cervix. Radiology 1965;84:709–716.PubMedGoogle Scholar
  5. 5.
    Harrison LB, Chadha M, Hill RJ, Hu K, Shasha D. Impact of tumor hypoxia and anemia on radiation therapy outcomes. The Oncologist 2002;7:492–508.PubMedCrossRefGoogle Scholar
  6. 6.
    Mundt AJ, et al. Race and clinical outcome in patients with carcinoma of the uterine cervix treated with radiation therapy. Gynecol Oncol 1998;71:151–158.PubMedCrossRefGoogle Scholar
  7. 7.
    Takeshi K, et al. Definitive radiotherapy combined with high-dose-rate brachytherapy for stage III carcinoma of the uterine cervix: retrospective analysis of prognostic factors concerning patient characteristics and treatment parameters. Int J Radiat Oncol Biol Phys 1998;41:319–327.PubMedCrossRefGoogle Scholar
  8. 8.
    Hong J-H, et al. The prognostic significance of pre- and posttreatment SCC levels in patients with squamous cell carcinoma of the cervix treated by radiotherapy. Int J Radiat Oncol Biol Phys 1998;41:823–830.PubMedCrossRefGoogle Scholar
  9. 9.
    Kagei K, et al. High-dose-rate intracavitary irradiation using linear source arrangement for stage II and III squamous cell carcinoma of the uterine cervix. Radiother Oncol 1998;47:207–213.PubMedCrossRefGoogle Scholar
  10. 10.
    Lee WR, et al. Anemia is associated with decreased survival and increased locoregional failure in patients with locally advanced head and neck carcinoma: a secondary analysis of RTOG 85-27. Int J Radiat Oncol Biol Phys 1998;42:1069–1075.PubMedCrossRefGoogle Scholar
  11. 11.
    Pedersen D, Søgaard H, Overgaard J, Bentzen SM. Prognostic value of pretreatment factors in patients with locally advanced carcinoma of the uterine cervix treated by radiotherapy alone. Acta Oncol 1995;34:787–795.PubMedCrossRefGoogle Scholar
  12. 12.
    Girinski T, et al. Prognostic value of hemoglobin concentrations and blood transfusions in advanced carcinoma of the cervix treated by radiation therapy: results of a retrospective study of 386 patients. Int J Radiat Oncol Biol Phys 1989;16:37–42.PubMedCrossRefGoogle Scholar
  13. 13.
    Vigario G, Kurohara SS, George FW III. Association of hemoglobin levels before and during radiotherapy with prognosis in uterine cervix cancer. Radiology 1973;106:649–652.PubMedGoogle Scholar
  14. 14.
    Surgenor DM, Wallace EL, Hao SHS, Chapman RH. Collection and transfusion of blood in the United States, 1982–1988. N Engl J Med 1990;322:1646–1651.PubMedCrossRefGoogle Scholar
  15. 15.
    Overgaard J. Sensitization of hypoxic tumour cells—clinical experience. Int J Radiat Biol 1989;56:801–811.PubMedCrossRefGoogle Scholar
  16. 16.
    Azuma C, et al. The influence of peri-operative blood transfusion during radical hysterectomy on the prognosis of uterine cervical cancer. Transfus Sci 1997;18:55–62.PubMedCrossRefGoogle Scholar
  17. 17.
    Eisenkop SM, et al. The clinical significance of blood transfusion at the time of radical hysterectomy. Obstet Gynecol 1990;76:110–113.PubMedGoogle Scholar
  18. 18.
    Lavey RS, Dempsey WH. Erythropoietin increases hemoglobin in cancer patients during radiation therapy. Int J Radiat Oncol Biol Phys 1993;27:1147–1152.PubMedCrossRefGoogle Scholar
  19. 19.
    Dusenbery KE, et al. Erythropoietin increases hemoglobin during radiation therapy for cervical cancer. Int J Radiat Oncol Biol Phys 1994;29:1079–1084.PubMedCrossRefGoogle Scholar
  20. 20.
    Henke M, Guttenberger R. Erythropoietin in radiation oncology—a review. 1st international conference, Freiburg, June 11–12, 1999. Oncology 2000;58:175–182.PubMedCrossRefGoogle Scholar
  21. 21.
    Sweeney PJ, et al. Effect of subcutaneous recombinant human erythropoietin in cancer patients receiving radiotherapy: final report of a randomized, open-labelled, phase II trial. Br J Cancer 1998;77:1996–2002.PubMedCrossRefGoogle Scholar
  22. 22.
    Saxena S, Rabinowitz AP, Johnson C, Shulman IA. Iron-deficiency anemia: a medically treatable chronic anemia as a model for transfusion overuse. Am J Med 1993;94:120–124.PubMedCrossRefGoogle Scholar
  23. 23.
    Pearcey R, et al. Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix. J Clin Oncol 2002;20:966–972.PubMedCrossRefGoogle Scholar
  24. 24.
    Thomas G. The effect of hemoglobin level on radiotherapy outcomes: the Canadian experience. Semin Oncol 2001;28:60–65.PubMedCrossRefGoogle Scholar
  25. 25.
    Dudrick SJ, O’Donnell JJ, Matheny RG, Unkel SP, Raleigh DP. Stimulation of hematopoiesis as an alternative to transfusion. South Med J 1986;79:669–673.PubMedCrossRefGoogle Scholar
  26. 26.
    Dudrick SJ, O’Donnell JJ, Raleigh DP, Matheny RG, Unkel SP. Rapid restoration of red blood cell mass in severely anemic surgical patients who refuse transfusion. Arch Surg 1985;120:721–727.PubMedCrossRefGoogle Scholar
  27. 27.
    Mamula P, Piccoli DA, Peck SN, Markowitz JE, Baldassano RN. Total dose intravenous infusion of iron dextran for iron-deficiency anemia in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2002;34:286–290.PubMedCrossRefGoogle Scholar
  28. 28.
    Sharma JB, et al. A prospective, partially randomized study of pregnancy outcomes and hematologic responses to oral and intramuscular iron treatment in moderately anemic pregnant women. Am J Clin Nutr 2004;79:116–122.PubMedGoogle Scholar
  29. 29.
    Beguin Y. Soluble transferrin receptor for the evaluation of erythropoiesis and iron status. Clin Chim Acta 2003;329:9–22.PubMedCrossRefGoogle Scholar
  30. 30.
    Fong Y, Karpeh M, Mayer K, Brennan MF. Association of perioperative transfusions with poor outcome in resection of gastric adenocarcinoma. Am J Surg 1994;167:256–260.PubMedCrossRefGoogle Scholar
  31. 31.
    Nilsson KR, et al. Preoperative predictors of blood transfusion in colorectal cancer surgery. J Gastrointest Surg 2002;6:753–762.PubMedCrossRefGoogle Scholar
  32. 32.
    Takemura M, Osugi H, Takada N, Kinoshita H, Higashino M. Immunologic effects of allogeneic versus autologous blood transfusion in patients undergoing radical oesophagectomy. Eur Surg Res 2003;35:115–122.PubMedCrossRefGoogle Scholar
  33. 33.
    Pysz M. Blood transfusions in breast cancer patients under-going mastectomy: possible importance of timing. J Surg Oncol 2000;75:258–263.PubMedCrossRefGoogle Scholar
  34. 34.
    Nosotti M, et al. Correlation between perioperative blood transfusion and prognosis of patients subjected to surgery for stage I lung cancer. Chest 2003;124:102–107.PubMedCrossRefGoogle Scholar
  35. 35.
    Asahara T, et al. Perioperative blood transfusion as a prognostic indicator in patients with hepatocellular carcinoma. World J Surg 1999;23:676–680.PubMedCrossRefGoogle Scholar
  36. 36.
    Taniguchi Y, Okura M. Prognostic significance of perioperative blood transfusion in oral cavity squamous cell carcinoma. Head Neck 2003;25:931–936.PubMedCrossRefGoogle Scholar
  37. 37.
    Blumberg N, Agarwal MM, Chuang C. A possible association between survival time and transfusion in cervical cancer. Yale J Biol Med 1988;61:493–500.PubMedGoogle Scholar
  38. 38.
    Vallejo RR, Hord ED, Barna SA, Santiago-Palma J, Ahmed S. Perioperative immunosuppression in cancer patients. J Environ Pathol Toxicol Oncol 2003;22:139–146.PubMedCrossRefGoogle Scholar
  39. 39.
    Vansteenkiste J, et al. Aranesp 980297 Study Group. Double-blind, placebo-controlled, randomized phase III trial of darbepoetin alfa in lung cancer patients receiving chemotherapy. J Natl Cancer Inst 2002;94:1211–1220.PubMedCrossRefGoogle Scholar
  40. 40.
    Dunphy FR, et al. Erythropoietin reduces anemia and transfusions: a randomized trial with or without erythropoietin during chemotherapy. Cancer 1999;86:1362–1367.PubMedCrossRefGoogle Scholar
  41. 41.
    Wurnig C, et al. Prevention of chemotherapy-induced anemia by the use of erythropoietin in patients with primary malignant bone tumors (a double-blind, randomized, phase III study). Transfusion 1996;36:155–159.PubMedCrossRefGoogle Scholar
  42. 42.
    Acs G, et al. Hypoxia-inducible erythropoietin signaling in squamous dysplasia and squamous cell carcinoma of the uterine cervix and its potential role in cervical carcinogenesis and tumor progression. Am J Pathol 2003;162:1789–1806.PubMedCrossRefGoogle Scholar
  43. 43.
    Yasuda Y, et al. Erythropoietin regulates tumour growth of human malignancies. Carcinogenesis 2003;24:1021–1029.PubMedCrossRefGoogle Scholar
  44. 44.
    Yasuda Y, et al. Inhibition of erythropoietin signalling destroys xenografts of ovarian and uterine cancers in nude mice. Br J Cancer 2001;84:836–843.PubMedCrossRefGoogle Scholar
  45. 45.
    Wun T, et al. Increased incidence of symptomatic venous thrombosis in patients with cervical carcinoma treated with concurrent chemotherapy, radiation and erythropoietin. Cancer 2003;98:1514–1520.PubMedCrossRefGoogle Scholar
  46. 46.
    Henke M, et al. Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial. Lancet 2003;362:1255–1260.PubMedCrossRefGoogle Scholar
  47. 47.
    Leyland-Jones B. BEST Investigators and Study Group. Breast cancer: trial with erythropoietin terminated unexpectedly. Lancet Oncol 2003;4:459–460.PubMedCrossRefGoogle Scholar
  48. 48.
    Flies AW, Milosevic M, Pintilie M, Syed A, Hill RP. Anemia, hypoxia and transfusion in patients with cervix cancer. Radiother Oncol 2000;57:13–19.CrossRefGoogle Scholar
  49. 49.
    Lee JW, Bae SH, Jeong JW, Kim SH, Kim KW. Hypoxia-inducible factor (HIF-1) alpha: its protein stability and biological functions. Exp Mol Med 2004;36:1–12.PubMedGoogle Scholar
  50. 50.
    Semenza GL. Involvement of hypoxia-inducible factor 1 in human cancer. Intern Med 2002;41:79–83.PubMedCrossRefGoogle Scholar
  51. 51.
    Srinivas V, Zhu X, Salceda S, Nakamura R, Caro J. Hypoxia-inducible factor 1alpha (HIF-1alpha) is a nonheme iron protein. Implications for oxygen sensing. J Biol Chem 1999;274:1180–1184.PubMedGoogle Scholar
  52. 52.
    Jeong HJ, et al. Expression of proinflammatory cytokines via HIF-1alpha and NF-kappaB activation on desferrioxamine-stimulated HMC-1 cells. Biochem Biophys Res Commun 2003;306:805–811.PubMedCrossRefGoogle Scholar
  53. 53.
    Obralic N, Bilenjki D, Bilbija Z. Prognostic importance of anemia related parameters in patients with carcinoma of the cervix uteri. Acta Oncol 1990;29:199–201.PubMedCrossRefGoogle Scholar
  54. 54.
    Auerbach M, et al. Intravenous iron optimizes the response to recombinant human erythropoietin in cancer patients with chemotherapy-related anemia: a multicenter, open-label, randomized trial. J Clin Oncol 2004;22:1301–1307.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2005

Authors and Affiliations

  • Myrna Candelaria
    • 1
  • Lucely Cetina
    • 1
  • Alfonso Dueñas-González
    • 2
    Email author
  1. 1.Division of Clinical ResearchInstituto Nacional de CancerologíaMexico City
  2. 2.Unidad de Investigación Biomédica en Cancer. Instituto Nacional de Cancerología-Instituto de Investigaciones BiomédicasUNAMMexico City

Personalised recommendations