U. S. Department of Heal Human Services

This review compares the efficacy and adverse effects of specific erythropoietic stimulants (i.e., epoetin alfa or beta], darbepoetin alfa) when used to manage anemia in patients undergoing cancer therapy (i.e., chemotherapy and/or radiation). This review also addresses questions relevant to optimizing the use of erythropoietic stimulants as a general class: the outcomes of using alternative thresholds to initiate or discontinue treatment and whether there are early predictors of response to treatment. Erythropoietin is an endogenous hormone, produced primarily in the kidney, which participates in regulating red blood cell production (erythropoiesis). Two forms of recombinant human erythropoietin-epoetin alfa and epoetin beta (the latter not commercially available in the United States)-have been extensively studied and used clinically for more than a decade to treat various anemias; they have similar clinical efficacy. In a recent review of safety concerns associated with recombinant human erythropoietins, a U. S. Food and Drug Administration (FDA) briefing document noted that "...the biochemical differences between various erythropoietin products are not associated with marked differences in the pharmacodynamic properties of the different products when used at recommended doses, thus effects observed with these non-US-licensed products may also be associated with the U. S. licensed product." Anemia (deficiency of red blood cells) occurs in 13-78 percent of patients undergoing treatment for solid tumors and 30-40 percent of patients treated for lymphoma. Tumor type, treatment regimen, and history of prior cancer therapy influence the risk and severity of anemia. This report focuses on use of epoetin or darbepoetin to manage anemia in patients undergoing cancer treatment with chemotherapy and/or radiation. Anemia severity is defined by hemoglobin (Hb) concentration. Erythropoietin, a hormone produced primarily in the kidney, participates in regulating red blood cell production (erythropoiesis) and thus Hb concentration. Two erythropoietic stimulants are available commercially in the United States, epoetin alfa (Epogen(R), Procrit(R)) and darbepoetin alfa (Aranesp(R)), which is a newer and longer acting drug. Epoetin beta, which is pharmacologically and clinically similar to epoetin alfa, is commercially available in Europe and elsewhere. Erythropoietic stimulants are widely used in clinical practice to manage anemia of patients undergoing cancer treatment and to reduce the need for transfusion. Although it is well established that erythropoietic stimulants improve anemia in patients undergoing cancer treatment, the comparative effectiveness of epoetin and darbepoetin has not been evaluated in a systematic review. Moreover, trials varied substantially in how erythropoietic stimulants have been used, including Hb concentration at start of treatment, doses given, treatment duration, and target Hb concentrations they sought to maintain. A review of these various trials may help maximize benefit, optimize drug usage, and minimize adverse effects from using erythropoietic stimulants to manage anemia in patients undergoing cancer treatment. The report addresses the following questions: 1. What are the comparative efficacy and safety of epoetin (alfa or beta) and darbepoetin? 2. How do alternative dosing strategies affect the comparative efficacy and safety of epoetin and darbepoetin? 3. How do alternative thresholds for initiating treatment or alternative criteria for discontinuing therapy or duration of therapy affect the efficacy and safety of erythropoietic stimulants? 4. Are any patient characteristics at baseline or early hematologic changes useful to select patients or predict responses to treatment with erythropoietic stimulants?

"Treating Tobacco Use and Dependence: 2008 Update"," is a product of the Tobacco Use and Dependence Guideline Panel, consortium representatives, consultants, and staff. This Guideline is an updated version that contains strategies and recommendations designed to assist clinicians; tobacco dependence treatment specialists; and health care administrators, insurers, and purchasers in delivering and supporting effective treatments for tobacco use and dependence. The recommendations were made as a result of a systematic review and meta-analysis of 11 specific topics identified by the Panel. The key recommendations of the updated Guideline are as follows: The overarching goal of these recommendations is that clinicians strongly recommend the use of effective tobacco dependence counseling and medication treatments to their patients who use tobacco, and that health systems, insurers, and purchasers assist clinicians in making such effective treatments available. 1. Tobacco dependence is a chronic disease that often requires repeated intervention and multiple attempts to quit. Effective treatments exist, however, that can significantly increase rates of long-term abstinence. 2. It is essential that clinicians and health care delivery systems consistently identify and document tobacco use status and treat every tobacco user seen in a health care setting. 3. Tobacco dependence treatments are effective across a broad range of populations. Clinicians should encourage every patient willing to make a quit attempt to use the counseling treatments and medications recommended in this Guideline. 4. Brief tobacco dependence treatment is effective. Clinicians should offer every patient who uses tobacco at least the brief treatments shown to be effective in this Guideline. 5. Individual, group, and telephone counseling are effective, and their effectiveness increases with treatment intensity. Two components of counseling are especially effective, and clinicians should use these when counseling patients making a quit attempt: Practical counseling (problemsolving/skills training); Social support delivered as part of treatment 6. Numerous effective medications are available for tobacco dependence, and clinicians should encourage their use by all patients attempting to quit smoking-except when medically contraindicated or with specific populations for which there is insufficient evidence of effectiveness (i.e., pregnant women, smokeless tobacco users, light smokers, and adolescents). Seven first-line medications (5 nicotine and 2 non-nicotine) reliably increase long-term smoking abstinence rates: Bupropion SR, Nicotine gum, Nicotine inhaler, Nicotine lozenge, Nicotine nasal spray, Nicotine patch, Varenicline; Clinicians also should consider the use of certain combinations of medications identified as effective in this Guideline. 7. Counseling and medication are effective when used by themselves for treating tobacco dependence. The combination of counseling and medication, however, is more effective than either alone. Thus, clinicians should encourage all individuals making a quit attempt to use both counseling and medication. 8. Telephone quitline counseling is effective with diverse populations and has broad reach. Therefore, both clinicians and health care delivery systems should ensure patient access to quitlines and promote quitline use. 9. If a tobacco user currently is unwilling to make a quit attempt, clinicians should use the motivational treatments shown in this Guideline to be effective in increasing future quit attempts. 10. Tobacco dependence treatments are both clinically effective and highly cost-effective relative to interventions for other clinical disorders. Providing coverage for these treatments increases quit rates. Insurers and purchasers should ensure that all insurance plans include the counseling and medication identified as effective in this Guideline as covered benefits.