ESA Label Revisions: The Saga Continues

On July 30, 2008 the US Food and Drug Administration (FDA) announced proposed changes to the approved labeling for the use of erythropoietin stimulating agents (ESAs). These changes are intended to clarify the FDA-approved conditions for use of ESAs in patients with cancer and revise directions for dosing to state the hemoglobin level at which treatment with an ESA should not be initiated. In March 2008, additional Black Box warnings were placed on the ESAs and stated the following:

1. ESAs shortened overall survival and/or time-to-tumor progression in clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers when dosed to target a hemoglobin of >12 g/dL.
2. The risks of shortened survival and tumor progression have not been excluded when ESAs are dosed to target a hemoglobin of <12 g/dL.
3. To minimize these risks, as well as the risk of serious cardiovascular and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusions.
4. Use only for the treatment of anemia due to concomitant myelosuppressive chemotherapy.

The changes announced on July 30, 2008, were as follows:

1. ESAs are approved for use only after a patient’s hemoglobin falls under 10 g/dL.
2. Label references to an upper limit of 12 g/dL have been eliminated.
3. ESAs are not indicated if the intent of chemotherapy is to cure a patient.

These changes have to potential to alter our selection of chemotherapy agents in the adjuvant setting, especially if specific regimens are known to be more likely to cause significant anemia.

Important clinical updates The 14th Annual Perspectives in Breast Cancer will provide physicians and nurses with valuable clinical updates in the field. Debates on controversial topics will provide significant insights into difficult patient management decisions. Clinicians and researchers from leading cancer centers and academic institutions will provide instruction about the latest developments. A preconference program on oncology symptom management will provide nurses and other healthcare professionals with a valuable supplement to the main meeting. September 26 – 27 in New York, New York.

FDA Legislation on Tobacco Products

Tobacco products, which kill approximately 440,000 people in America each year, are the only legally consumable products that are not regulated in the United States. On August 5, 2008, the House of Representatives passed, by a bipartisan, veto-proof majority of 326 to 102, legislation that will empower the FDA to regulate tobacco products. The House had never before voted on the FDA tobacco bill, which was first introduced in Congress 10 years ago. If enacted, the “Family Smoking Prevention Tobacco Control Act” would do the following:

• Ban marketing and sales of tobacco products to children
• Require disclosure of ingredients and larger, more specific health warnings
• Empower the FDA to require tobacco companies to reduce or eliminate harmful ingredients in their products
• Ban candy and fruit–flavored cigarettes
• Eliminate false health claims currently employed by the industry, such as "Light" and "Low Tar"

The bill now goes to the Senate, which has not yet scheduled a floor vote. The Senate bill currently has 57 cosponsors and is supported by members of both political parties. The American Cancer Society Cancer Action Network (ACS CAN), the nonprofit, nonpartisan advocacy partner of the American Cancer Society, follows this legislation as well as other cancer-related legislation closely. If you would like more information regarding cancer legislation, please visit their Website: www.acscan.org.

State of the art in management of NSCLC, SCLC and Esophageal Cancer The 13th Annual Perspectives in Thoracic Oncology will be held November 21 – 22 in New York, New York. This comprehensive overview will provide the latest information on the complex pathology and treatment of lung cancer, and will be presented by an internationally renowned faculty. Registration is now open!

Reducing Risk of Second Gastric Cancer After Resection of Early-Stage Gastric Cancer

Because the relation between Helicobacter pylori infection and gastric cancer has been shown in multiple studies, the aim of this open-label randomized trial was to investigate the prophylactic effect of H pylori eradication on the development of metachronous gastric carcinoma after endoscopic resection for early gastric cancer. The study consisted of 544 patients with early gastric cancer, either newly diagnosed and planning to have endoscopic treatment or in post-resection follow-up after endoscopic treatment. The patients were randomly assigned to either receive an H pylori eradication regimen (n = 272) or control (n = 272). Patients in the eradication group received lansoprazole 30 mg twice daily, amoxicillin 750 mg twice daily, and clarithromycin 200 mg twice daily for a week; those in the control group received standard care, but no treatment for H pylori. Patients were examined endoscopically at 6, 12, 24, and 36 months after randomization. The primary endpoint was diagnosis of new carcinoma at another site in the stomach. At 3-year follow-up, metachronous gastric carcinoma had developed in nine patients in the eradication group and 24 in the control group. In the full intention-to-treat population (272 patients in each group), the odds ratio for metachronous gastric carcinoma was 0.353 (95% CI, 0.161–0.775; P = .009). The authors suggested that prophylactic eradication of H pylori after endoscopic resection of early gastric cancer should be used to prevent the development of metachronous gastric carcinoma.

Fukase K, Kato M, Kikuchi S, et al. Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial. Lancet. 2008;372(9636):392-397.

Screening for Prostate Cancer: USPSTF Recommendation 2008

In 2002, the United States Preventive Services Task Force (USPSTF) last published their prostate cancer screening recommendations. At that time, their conclusion stated that there was insufficient evidence to recommend for or against screening for prostate cancer with prostate-specific antigen (PSA) testing. They have subsequently examined data published between 2002 and 2007 to understand the benefits and harms of screening men for prostate cancer with PSA. They included in their evaluation randomized, controlled trials and meta-analyses of PSA screening as well as studies of screening harms and the natural history of screen-detected cancer. They wished to answer the following questions:

1. Does screening with PSA as a single test or as a component of multiple tests decrease morbidity or mortality?
2. Other than overtreatment, what is the magnitude of the harms related to screening?
3. What is the natural history of PSA-detected, nonpalpable, localized prostate cancer?

Unfortunately, these questions cannot be completely answered by the available data. They stated that there were no completed good-quality randomized controlled trials of screening for prostate cancer. In addition, the natural history of PSA-detected prostate cancer is poorly understood. With regards to the second question, three of the evaluated studies suggested that false-positive PSA screening results caused psychological adverse events that lasted up to one year after the test. They did note, however, that two large randomized controlled trials of PSA screening are underway. In the first trial, 190,000 men between ages 50 – 75 years old have been randomly assigned to screening with PSA, digital rectal exam (DRE), and transrectal ultrasound (TRUS) or to standard care. The former assigned group was subsequently changed to PSA alone versus standard care. The second group is the United States National Cancer Institute (NCI) Prostate, Lung, Colorectal and Ovarian Cancer (PLCO)screening trial prostate group. This trial of 76,705 men is evaluating the effect of annual screening with PSA and DRE on prostate cancer-specific mortality.

Finally, with regards to specific populations, the USPSTF concluded that the currently published evidence is insufficient to balance the benefits and harms of prostate cancer screening in men younger than age 75 years, but they now recommend against screening in men age 75 years and older. They found with moderate certainty that the harms of screening for prostate cancer outweigh the benefits. Because of large gaps in available clinical trial data, as previously described, no specific recommendations can be made for other high-risk groups such as African American men and men with a family history of prostate cancer.

The American Cancer Society (ACS) last published an update of prostate cancer screening guidelines in 2001. The ACS recommends that the PSA blood test and DRE should be offered annually beginning at age 50 years to men who have a life expectancy of at least 10 years, and that a discussion take place with the patient about the potential benefits, limitations, and harms associated with testing. The ACS Prostate Cancer Advisory Committee placed strong emphasis on shared decision making between clinicians and patients, emphasizing that clinical policies of not discussing testing, discouraging testing, or recommending testing to all men were inappropriate. In addition, the Advisory Committee also concluded that if men ask the clinician to make the testing decision on their behalf following a discussion about benefits, limitations, and risks associated with prostate cancer testing, they should be tested unless other circumstances, ie, limited longevity, would discourage testing. Men at high risk, including men of sub-Saharan African descent and men with a first-degree relative diagnosed at a younger age (ie, <65 years), should begin testing at age 45 years. Men at even higher risk of prostate cancer due to more than one first-degree relative diagnosed with prostate cancer before age 65 years could begin testing at age 40 years, although if PSA is less than 1.0 ng/mL, no additional testing is needed until age 45 years. The ACS is also re-evaluating these screening guidelines and will report upon new recommendations when adequate data become available to justify such changes.

U.S. Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;149(3):185-191.

Smith RA, Cokkinides V, Eyre HJ. Cancer screening in the United States, 2007: a review of current guidelines, practices, and prospects. CA Cancer J Clin. 2007;57(2):90-104.

E-Learning: New Frontiers in Myeloma Management In this activity, four myeloma experts from the University of Texas M. D. Anderson Cancer Center have each taken a topic in myeloma management and expounded on treatment variables, obstacles and evidence-based strategies utilized at their center. Visit elc.imedex.com for accredited activities.

What's Next?

The 2008 Breast Cancer Symposium will be held in Washington, DC on September 5 – 7, 2008. Highlights from that meeting as well as other updates will be included in the next OncoFacts. Prior to the newsletter becoming available, video clips of interviews from the meeting will be broadcast on the Imedex E-Learning Center Website.

The next issue of OncoFacts™ will be in October 2008 and then monthly throughout the year.

OncoFacts™ Editor:

Christy Russell, MD

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