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Anemia response and safety to epoetin-beta treatment in patients with neoadjuvant therapy prior to primary digestive tract tumor surgery

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Abstract

Purpose

Anemia is common during anticancer treatment. This study aimed to evaluate the response and safety of treatment with epoetin-beta (EB) in patients with neoadjuvant therapy prior to primary digestive tract tumor surgery.

Patients and methods

In this open-label, single-arm study, patients (n = 22) with hemoglobin (Hb) levels below 11 g/dl who received epoetin-beta 450 IU/kg (30,000 IU) weekly until the hemoglobin level reached 12 g/dl.

Results

After treatment with EB, a mean absolute increment of 2.6 g/dl was attained. The mean hemoglobin values during the study were pretreatment 10.1 g/dl, half-way through treatment 12.3 g/dl, 4 weeks after concomitant radiochemotherapy 12.7 g/dl, the week prior to surgery 12.5 g/dl, and after surgery 10.9 g/dl. No patient required transfusion before or after surgery. The probability or risk of postoperative complications was 27.3%, and included one rectovaginal fistula, one parastomal hernia, one case of ileus and two surgical wound infections. In this series, downstaging was observed in 81.8% of patients, and downsizing in 90.9%. Most interestingly, histopathological complete response rate was achieved by 18.2%.

Conclusions

Epoetin-beta (EB) treatment in our series of patients with digestive malignancies subjected to neoadjuvant radiochemotherapy proved effective and safe, avoiding the need for transfusion during surgery.

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References

  1. Groopman JE, Itri LM (1999) Chemotherapy-induced anemia in adults: incidence and treatment. J Natl Cancer Inst 91:1616–1634

    Article  CAS  PubMed  Google Scholar 

  2. Ludwig H, Van Belle S, Barrett-Lee P, Birgegard G, Bokemeyer C, Gascon P, Kosmidis P, Krzakowski M, Nortier J, Olmi P, Schneider M, Schrijvers D (2004) The European Cancer Anaemia Survey (ECAS): a large, multinational, prospective survey defining the prevalence, incidence, and treatment of anaemia in cancer patients. Eur J Cancer 40:2293–2306

    Article  PubMed  Google Scholar 

  3. Tas F, Eralp Y, Basaran M, Sakar B, Alici S, Argon A, Bulutlar G, Camlica H, Aydiner A, Topuz E (2002) Anemia in oncology practice: relation to diseases and their therapies. Am J Clin Oncol 25:371–379

    Article  PubMed  Google Scholar 

  4. Cella D, Dobrez D, Glaspy J (2003) Control of cancer-related anemia with erythropoietic agents: a review of evidence for improved quality of life and clinical outcomes. Ann Oncol 14:511–519

    Article  CAS  PubMed  Google Scholar 

  5. Caro JJ, Salas M, Ward A, Goss G (2001) Anemia as an independent prognostic factor for survival in patients with cancer: a systemic, quantitative review. Cancer 91:2214–2221

    Article  CAS  PubMed  Google Scholar 

  6. Knight K, Wade S, Balducci L (2004) Prevalence and outcomes of anemia in cancer: a systematic review of the literature. Am J Med 116(Suppl 7A):11S–26S

    Article  PubMed  Google Scholar 

  7. Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, Quirke P, Couture J, de Metz C, Myint AS, Bessell E, Griffiths G, Thompson LC, Parmar M (2009) Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet 373:811–820

    Article  PubMed  Google Scholar 

  8. Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740

    Article  CAS  PubMed  Google Scholar 

  9. Rodel C, Martus P, Papadoupolos T, Fuzesi L, Klimpfinger M, Fietkau R, Liersch T, Hohenberger W, Raab R, Sauer R, Wittekind C (2005) Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol 23:8688–8696

    Article  PubMed  Google Scholar 

  10. Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF, Roussel A, Jacob JH, Segol P, Samama G et al (1994) Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer 73:2680–2686

    Article  CAS  PubMed  Google Scholar 

  11. Lee SH, Lee KC, Choi JH, Oh JH, Baek JH, Park SH, Shin DB (2008) Chemoradiotherapy followed by surgery in rectal cancer: improved local control using a moderately high pelvic radiation dose. Jpn J Clin Oncol 38:112–121

    Article  PubMed  Google Scholar 

  12. Voelter V, Schuhmacher C, Busch R, Peschel C, Siewert JR, Lordick F (2004) Incidence of anemia in patients receiving neoadjuvant chemotherapy for locally advanced esophagogastric cancer. Ann Thorac Surg 78:1037–1041

    Article  PubMed  Google Scholar 

  13. Berardi R, Braconi C, Mantello G, Scartozzi M, Del Prete S, Luppi G, Martinelli R, Fumagalli M, Valeri G, Bearzi I, Marmovale C, Grillo-Ruggieri F, Cascinu S (2006) Anemia may influence the outcome of patients undergoing neo-adjuvant treatment of rectal cancer. Ann Oncol 17:1661–1664

    Article  CAS  PubMed  Google Scholar 

  14. Box B, Lindsey I, Wheeler JM, Warren BF, Cunningham C, George BD, Mortensen NJ, Jones AC (2005) Neoadjuvant therapy for rectal cancer: improved tumor response, local recurrence, and overall survival in nonanemic patients. Dis Colon Rectum 48:1153–1160

    Article  PubMed  Google Scholar 

  15. Glimelius B, Linne T, Hoffman K, Larsson L, Svensson JH, Nasman P, Svensson B, Helmers C (1998) Epoetin beta in the treatment of anemia in patients with advanced gastrointestinal cancer. J Clin Oncol 16:434–440

    CAS  PubMed  Google Scholar 

  16. Suzuki Y, Tokuda Y, Fujiwara Y, Minami H, Ohashi Y, Saijo N (2008) Weekly epoetin beta maintains haemoglobin levels and improves quality of life in patients with non-myeloid malignancies receiving chemotherapy. Jpn J Clin Oncol 38:214–221

    Article  PubMed  Google Scholar 

  17. Strauss HG, Haensgen G, Dunst J, Hayward CR, Burger HU, Scherhag A, Koelbl H (2008) Effects of anemia correction with epoetin beta in patients receiving radiochemotherapy for advanced cervical cancer. Int J Gynecol Cancer 18:515–524

    Article  PubMed  Google Scholar 

  18. Pronzato P, Jassem J, Mayordomo J (2006) Epoetin beta therapy in patients with solid tumours. Crit Rev Oncol Hematol 58:46–52

    Article  PubMed  Google Scholar 

  19. Bokemeyer C, Aapro MS, Courdi A, Foubert J, Link H, Österborg A, Repetto L, Soubeyran P (2007) EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer: 2006 update. Eur J Cancer 43:258–270

    Article  CAS  PubMed  Google Scholar 

  20. Aapro M, Van Erps J, MacDonald K, Soubeyran P, Muenzberg M, Turner M, Warrinnier H, Albrecht T, Abraham I (2009) Managing cancer-related anaemia in congruence with the EORTC guidelines is an independent predictor of haemoglobin outcome: initial evidence from the RESPOND study. Eur J Cancer 45:8–11

    Article  PubMed  Google Scholar 

  21. Aapro MS, Birgegard G, Bokemeyer C, Cornes P, Foubert J, Gascon P, Glaspy J, Hellstrom-Lindberg E, Link H, Ludwig H, Osterborg A, Repetto L, Soubeyran P (2008) Erythropoietins should be used according to guidelines. Lancet Oncol 9:412–413

    Article  PubMed  Google Scholar 

  22. Cheer SM, Wagstaff AJ (2004) Epoetin beta: a review of its clinical use in the treatment of anaemia in patients with cancer. Drugs 64:323–346

    Article  CAS  PubMed  Google Scholar 

  23. Salgado M, Gómez A, Valladares M, Jorge M, Carballo A (2008) Efficacy of epoetin-beta 30,000 iu/week in correcting anemia in patients with gastrointestinal tumors subjected to concomitant chemo-radiotherapy. In: ASCO. Gastrointestinal cancers symposium. Category: Colon and rectum—multidisciplinary treatment, abstract no: 517

  24. Rizzo JD, Somerfield MR, Hagerty KL, Seidenfeld J, Bohlius J, Bennett CL, Cella DF, Djulbegovic B, Goode MJ, Jakubowski AA, Rarick MU, Regan DH, Lichtin AE (2008) Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Clinical Oncology/American Society of Hematology clinical practice guideline update. J Clin Oncol 26:132–149

    Article  CAS  PubMed  Google Scholar 

  25. Abbrederis K, Bassermann F, Schuhmacher C, Voelter V, Busch R, Roethling N, Sendler A, Siewert JR, Peschel C, Lordick F (2006) Erythropoietin-alfa during neoadjuvant chemotherapy for locally advanced esophagogastric adenocarcinoma. Ann Thorac Surg 82:293–297

    Article  PubMed  Google Scholar 

  26. Chao M, Gibbs P, Tjandra J, Cullinan M, McLaughlin S, Faragher I, Skinner I, Jones I (2005) Preoperative chemotherapy and radiotherapy for locally advanced rectal cancer. ANZ J Surg 75:286–291

    Article  PubMed  Google Scholar 

  27. Suarez J, Vera R, Balen E, Gomez M, Arias F, Lera JM, Herrera J, Zazpe C (2008) Pathologic response assessed by Mandard grade is a better prognostic factor than down staging for disease-free survival after preoperative radiochemotherapy for advanced rectal cancer. Colorectal Dis 10:563–568

    Article  CAS  PubMed  Google Scholar 

  28. Vecchio FM, Valentini V, Minsky BD, Padula GD, Venkatraman ES, Balducci M, Micciche F, Ricci R, Morganti AG, Gambacorta MA, Maurizi F, Coco C (2005) The relationship of pathologic tumor regression grade (TRG) and outcomes after preoperative therapy in rectal cancer. Int J Radiat Oncol Biol Phys 62:752–760

    PubMed  Google Scholar 

  29. Bouzourene H, Bosman FT, Seelentag W, Matter M, Coucke P (2002) Importance of tumor regression assessment in predicting the outcome in patients with locally advanced rectal carcinoma who are treated with preoperative radiotherapy. Cancer 94:1121–1130

    Article  PubMed  Google Scholar 

  30. Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ (2001) Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 345:638–646

    Article  CAS  PubMed  Google Scholar 

  31. No_authors_listed (1997) Improved survival with preoperative radiotherapy in resectable rectal cancer. Swedish rectal cancer trial. N Engl J Med 336:980–987

    Google Scholar 

  32. Benzoni E, Intersimone D, Terrosu G, Bresadola V, Cojutti A, Cerato F, Avellini C (2006) Prognostic value of tumor regression grading and depth of neoplastic infiltration within the perirectal fat after combined neoadjuvant radiochemotherapy and surgery for rectal cancer. J Clin Pathol 59:505–512

    Article  CAS  PubMed  Google Scholar 

  33. Das P, Skibber JM, Rodriguez-Bigas MA, Feig BW, Chang GJ, Wolff RA, Eng C, Krishnan S, Janjan NA, Crane CH (2007) Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer. Cancer 109:1750–1755

    Article  CAS  PubMed  Google Scholar 

  34. Tran CL, Udani S, Holt A, Arnell T, Kumar R, Stamos MJ (2006) Evaluation of safety of increased time interval between chemoradiation and resection for rectal cancer. Am J Surg 192:873–877

    Article  PubMed  Google Scholar 

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Acknowledgments

We gratefully acknowledge the assistance of Dr Cristina Fernández for statistical data analysis and Carlos Lisbona (LIDESEC SL) for providing medical writing and editing services. This study was supported by F. Hoffmann-La Roche Ltd. The trial was designed, implemented and overseen by Dr Antonio Gómez Caamaño. The sponsor assisted in the collection and analysis of data. Responsibility for opinions, conclusions and interpretation of data lies with the authors.

Conflict of interest statement

Antonio Gómez, Mercedes Salgado, Manuel Valladares-Ayerbes, Mónica Jorge, Ana Carballo, Sonia Candamio, Pilar Izquierdo and Rafael López do not have any financial interests, such as stock ownership, or employment for any company. Antonio Gómez and Ana Carballo received remuneration from Roche Farma S.A., Manuel Valladares-Ayerbes had a consultant/advisory role with Amgen and Merck. Rafael López received funding from Sanofi Aventis, Pfizer and Almirall. Mercedes Salgado, Mónica Jorge, Sonia Candamio, Pilar Izquierdo and Enrique Castro have nothing to disclosure.

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Authors and Affiliations

  1. Servicio Oncología Radioterápica, Hospital Clínico Universitario Santiago de Compostela, Travesia Choupana S/N, 15706, Santiago de Compostela, Spain

    Antonio Gómez, Ana Carballo & Sonia Candamio

  2. Servicio Oncología Médica, Complejo Hospitalario de Orense, Orense, Spain

    Mercedes Salgado

  3. Servicio Oncología Médica, Complejo Hospitalario de La Coruña, La Coruña, Spain

    Manuel Valladares-Ayerbes

  4. Servicio Oncología Médica, Complejo Hospitalario de Vigo, Vigo, Spain

    Mónica Jorge

  5. Servicio de Oncología Radioterápica, Complejo Hospitalario de Orense, Orense, Spain

    Enrique Castro

  6. Servicio Oncología Médica, Hospital Clínico Universitario Santiago de Compostela, Santiago de Compostela, Spain

    Rafael López

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  1. Antonio Gómez
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  8. Rafael López
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Corresponding author

Correspondence to Antonio Gómez.

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Gómez, A., Salgado, M., Valladares-Ayerbes, M. et al. Anemia response and safety to epoetin-beta treatment in patients with neoadjuvant therapy prior to primary digestive tract tumor surgery. Cancer Chemother Pharmacol 66, 567–573 (2010). https://doi.org/10.1007/s00280-009-1197-0

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  • DOI: https://doi.org/10.1007/s00280-009-1197-0

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