Management of Anemia in Patients Receiving Chemotherapy
Authors: Justin S. Waters, Mary E.R. O’Brien, Sue Ashley, T. J. Littlewood, E. Bajetta, J. W.R. Nortier, E. Vercammen, B. Rapoport
Journal: Journal of Clinical Oncology (2002)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.2.601 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11786593 Management of Anemia in Patients Receiving Chemotherapy Justin S. WatersxJustin S. WatersSearch for articles by this author , Mary E.R. O'BrienxMary E.R. O'BrienSearch for articles by this author , Sue AshleyxSue AshleySearch for articles by this author T. J. LittlewoodxT. J. LittlewoodSearch for articles by this author , E. BajettaxE. BajettaSearch for articles by this author , J. W.R. NortierxJ. W.R. NortierSearch for articles by this author , E. VercammenxE. VercammenSearch for articles by this author , B. RapoportxB. RapoportSearch for articles by this author , Show More Royal Marsden Hospital, Sutton, Surrey, United KingdomJohn Radcliffe Hospital, Oxford, United Kingdom https://doi.org/10.1200/JCO.2002.20.2.601 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse15012002In Reply:We thank Waters et al for their insightful and informative remarks. They have highlighted both the importance of hemoglobin (Hb) levels with respect to therapeutic outcome in cancer patients and the multiple benefits that may accrue with administration of epoetin alfa to increase Hb levels in anemic cancer patients.The results of our study,1 as well as those of three large, community-based trials in over 7,000 patients,2-4 have demonstrated that epoetin alfa therapy significantly increases Hb levels in anemic cancer patients, with subsequent improvement in a number of quality-of-life (QOL) domains known to be negatively impacted by cancer-related anemia (Cancer Linear Analog Scale/Linear Analog Scale Assessment: energy level, ability to do daily activities, and overall QOL subscales; Functional Assessment of Cancer Therapy–Anemia: anemia subscale). Further, these studies provided data enabling our group and other investigators to determine the optimal target level for Hb, ie, that level which will result in the greatest incremental gain in QOL. In a marginal analysis of data from each of the aforementioned community-based studies, the greatest incremental gains in QOL were found to have occurred when Hb levels increased from 11 to 12 g/dL (range, 11 to 13 g/dL).2-5 Similarly, an incremental analysis of data from our own placebo-controlled study showed that the greatest positive changes in QOL were associated with a final Hb level of approximately 13 g/dL.6 QOL continued to improve as Hb increased to 14 g/dL but at a slower rate. Together, the results of these analyses suggest that a target level of 12 to 13 g/dL will produce the greatest gains in QOL and that treatment of anemia should therefore begin well before the Hb level decreases dramatically below 10 g/dL.Interestingly, Hb levels in the 12- to 13-g/dL range also seem to be important for patients' response to cancer therapy and overall survival. In their letter, Waters et al noted that a retrospective review of data for lung cancer patients treated at their institution over the last decade showed better survival rates for patients with nadir Hb levels above 12 g/dL throughout chemotherapy, compared with those whose nadir Hb levels were below this level. This observation is consistent with the findings of other studies, which suggest that anemia in cancer patients may lead to poor tolerance of chemotherapy and radiation therapy, decreased locoregional tumor control, and decreased survival time.7 In a retrospective study, long-term outcomes were evaluated for patients who received radiotherapy for squamous cell tumors of the head and neck. In this study, the estimated 5-year survival rate for patients with Hb levels ≥ 13 g/dL for men and ≥ 12 g/dL for women was 58%, compared with 28% for patients with Hb levels below these respective values.8 Also, significantly higher rates of overall relapse, local recurrence, and distant metastases have been reported for patients with average weekly nadir Hb levels of less than 12 g/dL during radiotherapy, compared with patients whose average weekly nadir Hb levels were ≥ 12 g/dL.9These findings and those of earlier investigators have prompted efforts to correct low Hb levels in anemic cancer patients, with the goal of improving therapeutic outcome. One option for doing this has been transfusion of RBCs. However, as demonstrated in our study, although transfusions can stabilize Hb levels, they can not prevent deterioration of QOL and may fail to provide any survival benefit (our study showed a trend in overall survival favoring epoetin alfa over placebo, although the study was not powered for survival as an end point1). In contrast, a growing body of evidence indicates that epoetin alfa therapy, by increasing Hb levels, may provide a survival benefit in addition to improving QOL. In a study in patients receiving chemoradiation for squamous cell carcinoma of the oral cavity and oropharynx, Glaser et al10 found significantly higher response, locoregional control, and survival rates in patients with pretreatment Hb of ≥ 14.5 g/dL or less than 14.5 g/dL given epoetin alfa, compared with patients with levels less than 14.5 g/dL not given epoetin alfa.10Additional evidence of a survival benefit with epoetin alfa is emerging from studies in animal models. In a recently reported preclinical study, Mittelman et al11 evaluated the biologic effects of epoetin alfa on the course of tumor progression, using murine myeloma models. In one model (MOPC-315-IgAλ2), daily treatment with epoetin alfa induced complete and permanent tumor regression in 30% to 60% of mice, an effect that was shown to be attributable to a T-cell–mediated mechanism. The investigators indicated that erythropoietin may have an intrinsic antitumor effect in addition to its RBC-stimulating activity.In summary, there is now convincing evidence that Hb may be an independent prognostic factor for treatment outcomes, as alluded to by Waters et al, and that treating cancer-related anemia with epoetin alfa can provide multiple benefits for patients, including improved QOL, and, possibly, increased survival time. However, further study is necessary to more fully explore and define the potential of this agent.1. Littlewood TJ, Bajetta E, Nortier JW, et al: Effects of epoetin alfa on hematologic parameters and quality of life in cancer patients receiving nonplatinum chemotherapy: Results of a randomized, double-blind, placebo-controlled trial. J Clin Oncol 19:: 2865,2001–2874, Link, Google Scholar2. Glaspy J, Bukowski R, Steinberg D, et al: Impact of therapy with epoetin alfa on clinical outcomes in patients with nonmyeloid malignancies during cancer chemotherapy in community oncology practice. J Clin Oncol 15:: 1218,1997–1234, Link, Google Scholar3. Demetri GD, Kris M, Wade J, et al: Quality-of-life benefit in chemotherapy patients treated with epoetin alfa is independent of disease response or tumor type: Results from a prospective community oncology study. J Clin Oncol 16:: 3412,1998–3425, Link, Google Scholar4. Gabrilove JL, Cleeland CS, Livingston RB, et al: Clinical evaluation of once-weekly dosing of epoetin alfa in chemotherapy patients: Improvements in hemoglobin and quality of life are similar to three-times-weekly dosing. J Clin Oncol 19:: 2875,2001–2882, Link, Google Scholar5. Cleeland CS, Demetri GD, Glaspy J, et al: Identifying hemoglobin level for optimal quality of life: Results of an incremental analysis. Proc Am Soc Clin Oncol 18:: 574a,,1999 (abstr 2215) Google Scholar6. Baietta E, Nortier JWR: Effects of epoetin alfa on quality of life (QOL) in breast cancer (BC) patients (Pts) receiving nonplatinum (NP) chemotherapy (CT): A subopulation analysis. Ann Oncol 11:: 149,,2000 (abstr 684P; suppl 4) Google Scholar7. Pecorelli S: Suboptimal hemoglobin levels: Do they impact patients and their therapy? Introduction. Semin Oncol 27:: 1,2000–3, (suppl 4) Google Scholar8. Frommhold H, Guttenberger R, Henke M: The impact of blood hemoglobin content on the outcome of radiotherapy: The Freiburg experience. Strahlenther Onkol 174:: 31,1998–34, (suppl 4) Google Scholar9. Grogan M, Thomas GM, Melamed I, et al: The importance of hemoglobin levels during radiotherapy for carcinoma of the cervix. Cancer 86:: 1528,1999–1536, Crossref, Medline, Google Scholar10. Glaser CM, Millesi W, Kornek GV, et al: Impact of hemoglobin level and use of recombinant erythropoietin on efficacy of preoperative chemoradiation therapy for squamous cell carcinoma of the oral cavity and oropharynx. Int J Radiat Oncol Biol Phys 50:: 705,2001–715, Crossref, Medline, Google Scholar11. Mittelman M, Neumann D, Peled A, et al: Erythropoietin induces tumor regression and antitumor immune responses in murine myeloma models. Proc Natl Acad Sci U S A 98:: 5181,2001–5186, Crossref, Medline, Google Scholar