To the Editor: Khuri (June 14 issue)1 highlights safety concernsregarding the use of erythropoiesis-stimulating agents (ESAs)in patients with cancer. The studies that have given rise tothese concerns used significantly higher hemoglobin targetsthan those used in the community or recommended in widely usedguidelines,2,3 and thus do not reflect the current standardof care. The only study that did not use an excessively highhemoglobin target has not been published and cannot be accuratelyreviewed.
In these studies, treatment with ESAs was initiated in patientswith hemoglobin levels as high as 14.5 g per deciliter. Manyof these patients never would have received ESAs in the community,where the use of ESAs is generally initiated at hemoglobin levelsbelow 10 to 11 g per deciliter.
Treatment with ESAs has been of enormous benefit to patientswith cancer who have anemia, improving their quality of lifeand decreasing the need for blood transfusions.4,5,6 The safetyand efficacy of ESAs, when used in accordance with current guidelines,are well established.
Revising the appropriate standard of care for ESA use in patientswith cancer requires evidence of either an inferior outcomewith the current standard or a superior outcome with a differentapproach. Studies that use excessively high hemoglobin targetssimply indicate that ESAs should not be used excessively; theydo not indicate that the current standard of care is harmful.
Stephen C. Lattanzi, M.D. Connecticut Oncology Association Waterford, CT 06385 s.c.lattanzi{at}gmail.com
References
Khuri FR. Weighing the hazards of erythropoiesis stimulation in patients with cancer. N Engl J Med 2007;356:2445-2448. [Free Full Text]
Rizzo JD, Lichtin AE, Woolf SH, et al. Use of epoetin in patients with cancer. Alexandria, VA: American Society of Clinical Oncology, 2007. (Accessed August 29, 2007, at http://www.asco.org.)
Cella D, Kallich J, McDermott A, Xu X. The longitudinal relationship of hemoglobin, fatigue and quality of life in anemic cancer patients: results from five randomized clinical trials. Ann Oncol 2004;15:979-986. [Free Full Text]
Glaspy JA, Jadeja JS, Justice G, Fleishman A, Rossi G, Colowick AB. A randomized, active-control, pilot trial of front-loaded dosing regimens of darbepoetin-alfa for the treatment of patients with anemia during chemotherapy for malignant disease. Cancer 2003;97:1312-1320. [CrossRef][ISI][Medline]
Vansteenkiste J, Pirker R, Massuti B, et al. 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. [Free Full Text]
The author replies: Achieving the right balance in the use ofESAs in oncology requires a review of the relevant clinicaldata made available by the Oncology Drug Advisory Committeeof the Food and Drug Administration (FDA).1 ESAs were initiallyapproved for chemotherapy-related anemia (not anemia of cancer)on the basis of data from six randomized, placebo-controlled,double-blind clinical trials involving 131 patients with cancerand anemia who were receiving concurrent chemotherapy with orwithout epoetin alfa (Procrit).2 Despite the expanded indicationsfor both erythropoietin and darbepoetin, no improvements inquality of life were shown.
Misinterpretation of these data has led to the current stateof affairs: according to Amgen Pharmaceuticals, 12 to 16% ofESA use in patients with cancer is initiated at hemoglobin levelsabove 12 g per deciliter.3 As I mentioned in my Perspectivearticle, randomized trials seeking to elevate hemoglobin levelsto normal levels showed incontrovertible evidence of harm, includingaccelerated cancer progression and increased thrombovascularevents. This evidence prompted the FDA's black-box warning prohibitingthe initiation of ESA use at hemoglobin levels above 10 g perdeciliter.1 Given these and additional data suggesting thatanemia associated with chronic disease is a compensatory physiologicresponse to the chronic condition, these warnings are justifiable.4Although ESAs are effective in reducing transfusion requirementsand mitigating severe anemia in patients with cancer who areundergoing chemotherapy, attempts to expand the indicationsfor their use in oncology have been unsuccessful. Ignoring availabledata on ESAs is unlikely to benefit patients with cancer.
Fadlo R. Khuri, M.D. Emory Winship Cancer Institute Atlanta,GA 30322
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