Caution Regarding Use Of Erythropoiesis-Stimulating Agents In Cancer Patients Recommended In New Guideline

An updated joint guideline by the American Society of Hematology (ASH), the world’s largest professional society concerned with the causes and treatment of blood disorders, and the American Society of Clinical Oncology (ASCO) advises physicians about the appropriate use of erythropoiesis-stimulating agents (ESAs), a class of drugs that stimulate the bone marrow to produce more red blood cells, to treat cancer patients with chemotherapy-induced anemia.

While the guideline cautions that ESAs are associated with shorter survival and increased risk of thromboembolism — blood clots — tumor progression and stroke, it also recognizes their major benefit of reducing the need for red blood cell transfusions, which can potentially cause serious infections and adverse reactions in the immune system.

“This updated guideline offers clinicians the latest synthesis of the medical evidence surrounding use of ESAs in patients with cancer, including appropriate cautions where evidence is lacking or where risks may outweigh the use of ESAs,” said J. Douglas Rizzo, MD, MS, Co-Chair of the guideline panel and Professor of Medicine at the Medical College of Wisconsin.

Those risks may include thromboembolism or even death, according to new data cited in the guideline, which suggests that physicians avoid the use of ESAs in cancer patients who are not receiving chemotherapy, except for those with myelodysplastic syndrome (MDS). At the same time, the guideline confirms the effectiveness of ESAs in sparing patients the need for transfusions, which can substantially impact Quality of Life. By recommending that physicians discuss individual risks and benefits of ESAs and blood transfusion with patients prior to therapy, the guideline recognizes the critical role of shared decision-making between the patient and the physician.

In addition to outlining the clotting risks of ESAs, the guideline makes specific recommendations on usage and provides insights into disease progression and patient survival. The guideline also details new thresholds for initiation and modification of ESAs, which are consistent with current US FDA labeling.

Originally published in 2002 and last updated in 2007, the guideline was derived from analysis of individual patient data, various medical literature, and systematic reviews of published clinical trials. In developing the update, panel members considered all relevant literature published between January 2007 and January 2010. Additional evidence was considered when it was considered pertinent to each section of the updated guideline.

“These guidelines touch on almost all aspects of the use of ESAs in patients with cancer and MDS, as well as secondary issues, such as the role of iron supplementation,” said Samuel Silver, MD, a member of ASH’s Committee on Practice and Professor of Internal Medicine at the University of Michigan. “These are issues that confront practicing hematologists and oncologists on a daily basis, and we hope that these evidence-based recommendations will influence practice standards and result in better care for patients.”

For more information:
Rizzo JD, Brouwers M, Hurley P, Seidenfeld J, Arcasoy MO, Spivak JL, Bennett CL, Bohlius J, Evanchuk D, Goode MJ, Jakubowski AA, Regan DH, Somerfield MR. American Society of Clinical Oncology/American Society of Hematology Clinical Practice Guideline Update on the Use of Epoetin and Darbepoetin in Adult Patients With CancerJ Clin Oncol. 2010 Nov 20;28(33):4996-5010. Epub 2010 Oct 25.

This article was first published online at Onco'Zine - The International Cancer Network

FDA approves New Single-Pill Combination of valsartan and aliskiren to Treat High Blood Pressure

The US Food and Drug Administration (FDA) has approved a new single-pill combination of aliskiren and valsartan tablets (Valturna; Novartis AG, Basel, Switzerland), the first and only medicine to target two key points within the renin system, also known as the renin angiotensin aldosterone system or RAAS, an important regulator of blood pressure.

This is the first approval for the single-pill combination of aliskiren and valsartan, which is indicated for the treatment of high blood pressure in patients not adequately controlled on aliskiren or angiotensin receptor blocker (ARB) monotherapy and as initial therapy in patients likely to need multiple drugs to achieve their blood pressure goals.

"This unique combination brings together the powerful blood pressure lowering effects of valsartan and aliskiren," said Joe Jimenez, CEO of the Novartis Pharmaceuticals Division. "It offers an important additional treatment option for physicians and hypertension patients, many of whom are not at their blood pressure goal. Valturna builds upon our strong cardiovascular franchise and is consistent with our long-term commitment to developing effective and innovative therapies. It further strengthens our growing portfolio of single-pill combinations to treat high blood pressure."

The new single-pill combines in a single pill valsartan, the active ingredient in Diovan , the number one selling branded high blood pressure medicine worldwide, and aliskiren, the active ingredient in Tekturna, the only approved direct renin inhibitor (DRI). The combination offers significantly greater blood pressure reduction than either valsartan or aliskiren alone.

"When it comes to diagnosing and treating high blood pressure, there is a real need for innovative therapies that help patients get to a healthier blood pressure range," said John Flack, M.D., Valturna investigator, and Chairman of the Department of Internal Medicine, Wayne State University, Detroit. "Now for the first time, we have a treatment option in one pill that targets two key points of the RAAS, which may be overactive in many hypertensive patients."

This approval was primarily based on a pivotal eight-week randomized, double-blind, placebo-controlled clinical trial in approximately 1,800 patients, which studied aliskiren 150 mg and 300 mg and valsartan 160 mg and 320 mg alone and in combination. The initial doses of aliskiren and valsartan were 150 mg and 160 mg, respectively, and were increased at four weeks to 300 mg and 320 mg, respectively.

Blood pressure reductions with the aliskiren/valsartan combination were significantly greater than with the monotherapies or placebo at the eight-week primary endpoint. Mean systolic and diastolic blood pressure reductions from baseline were 17.2/12.2 mmHg for aliskiren 300 mg/valsartan 320 mg, compared with 12.8/9.7 mmHg for valsartan 320 mg, 13.0/9.0 mmHg for aliskiren 300 mg, and 4.6/4.1 mmHg for placebo (p<0.05>.

For more information, read these PubMed abstracts:

Yamamoto E, Kataoka K, Dong YF, Nakamura T, Fukuda M, et al. Aliskiren enhances the protective effects of valsartan against cardiovascular and renal injury in endothelial nitric oxide synthase-deficient mice. Hypertension. 2009 Sep;54(3):633-8. Epub 2009 Jul 13.

• Geiger H, Barranco E, Gorostidi M, Taylor A, et al. Combination therapy with various combinations of aliskiren, valsartan, and hydrochlorothiazide in hypertensive patients not adequately responsive to hydrochlorothiazide alone. J Clin Hypertens (Greenwich). 2009 Jun;11(6):324-32.
• Yarows SA, Oparil S, Patel S, Fang H, Zhang J. Aliskiren and valsartan in stage 2 hypertension: subgroup analysis of a randomized, double-blind study.
  Adv Ther. 2008 Dec;25(12):1288-302.
• Tato AM, García López F. [Is the combination aliskiren /valsartan as effective and safe as either drug in monotherapy for treating hypertension?] Nefrologia. 2008;28 Suppl 2:10-1. (Spanish).
• Oparil S, Yarows SA, Patel S, Fang H, Zhang J, Satlin A. Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension: a randomised, double-blind trial. Lancet. 2007 Jul 21;370(9583):221-9
• Chrysant SG, Murray AV, Hoppe UC, Dattani D, Patel S, Hsu H, Zhang J. Long-term safety, tolerability and efficacy of aliskiren in combination with valsartan in patients with hypertension: a 6-month interim analysis. Curr Med Res Opin. 2008 Apr;24(4):1039-47. Epub 2008 Feb 27.