Internal Medicine News www.internalmedicinenews.com VOL. 43, NO. 9 The Leading Independent Newspaper for the Internist—Since 1968 M AY 15, 2010 WHAT’S NEW ACP Aims to Eliminate Improper Use of Therapies and Diagnostics

The United States spends A change in medical school $700 billion per year on tests curriculum may be needed to reflect the realities of health care and procedures that do not reform. 10 improve health outcomes.

More findings from ACCORD BY MARY ELLEN SCHNEIDER help identify which patients are EWS at higher risk from intensive N T ORONTO — The American College glucose control. 13

of Physicians will soon begin issuing EDICAL recommendations aimed at eliminating M Is bariatric surgery appropriate overused and misused diagnostic studies LOBAL for teens? Mindful Practice and treatments that do nothing to im- G columnists examine the issue. 20 prove patient care.

The High-Value, Cost-Conscious LSEVIER Gene signatures may predict Care Initiative, which was launched at /E

recurrence of hepatocellular IERCE

the ACP’s annual meeting in April, will P carcinoma. 26 compare treatments and diagnostics for ALVIN

a number of diseases and assess their C Anti-TNF agents may have benefits, harms, and costs. The ACP’s The ACP plans to focus specifically on issues of overuse and misuse of beneficial cardiac effects in Clinical Efficacy Assessment Technical ineffective treatments, said Dr. Steven E. Weinberger (left). “Doing more isn’t rheumatoid arthritis patients. 31 Advisory Committee will make the rec- necessarily always doing better,” said Dr. Paul G. Shekelle (right). ommendations and submit them to the The pandemic Annals of Internal Medicine for publi- ommendations, ACP leaders said at the ative screening tests, for example. Addi- influenza cation. annual meeting. These recommenda- tional recommendations will follow over A(H1N1) virus They plan to start with the “low-hang- tions, which will be issued in the next the next several months. now accounts ing fruit” in health care where there is al- few months, could include evaluations of “We feel that physicians really need to for almost all ready sufficient evidence to make rec- the appropriateness of certain preoper- See ACP page 3 influenza cases in the United States. 32 Tamoxifen and Raloxifene Hold ‘The important message is that Deep brain stimulation for both [drugs] are options. Parkinson’s disease: Different Up as Breast Cancer Prevention ’ areas of the brain may be targeted. 40 BY KERRI WACHTER thromboembolic complications, and the American Association for Cancer Re- cataracts. search. The results were also published Law & Medicine WASHINGTON — Tamoxifen and “These data are good news for post- in the journal Cancer Prevention Re- columnist explains raloxifene offer women at high-risk of menopausal women who want to reduce search (2010 April 19 [doi:10.1158/1940- the exceptions to developing breast cancer two effective their risk of breast cancer,” said Dr. D. 6207.CAPR-10-0076]). disclosure. 48 options to prevent the disease, based on Lawrence Wickerham, associate chair- Oncologists at the meeting expressed 8 years of follow-up data for more than man of the National Surgical Adjuvant frustration that more women at high risk EHR Report columnists detail the 19,000 women in the STAR trial. Breast and Bowel Project (NSABP). “The are not on the drugs, given the proven ef- benefits and pitfalls of becoming While tamoxifen proved significantly important message is that both [drugs] ficacy of the two selective estrogen re- a paperless office. 51 more effective in preventing invasive are options. The decision is a shared one ceptor modulators (SERMs) in prevent- breast cancer, there was no significant between the patient and her physician.” ing breast cancer. “I have to ask, why Widespread adoption of EHRs difference between the two drugs in pre- Dr. Wickerham presented the latest re- aren’t the results of the BCPT [breast can be an integral part of quality venting noninvasive breast cancer. And sults for the Study of Tamoxifen and cancer prevention trial] and STAR trials improvement, the ACP says. 52 raloxifene (Evista) had significantly less Raloxifene (STAR) trial during a late- more vigorously applied in clinical prac- toxicity, including endometrial cancer, breaker session at the annual meeting of See Prevention page 5

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SERMs Effective but Underused ty of Texas M.D. Anderson Cancer Cen- ter in Houston, identified several factors Prevention from page 1 that may be responsible for limited use of tamoxifen and raloxifene for prevention. tice?” said Dr. Gabriel N. Hortobagyi, relative risk of invasive breast cancer on He cited misinformation about the drugs, who was the invited discussant. raloxifene was 1.24 compared with ta- fears about toxicities, limited high-risk Dr. Wickerham echoed this frustration moxifen, which was significant. Both prediction tools, lack of a marker or mea- during a press conference. “I see women drugs reduced the risk of invasive breast surement to monitor for risk reduction, each week, at a high risk of breast can- cancer by roughly 50% in the original re- cost, and insufficient public and profes- cer, and I will end up telling one or two port (median follow-up 47 months). sional education about the drugs. EWS of them ...all too often ...that they have In this analysis, “we have estimated, N “There is no perfect drug. Certainly in breast cancer. I’d love for that part of my however, that this difference in the ralox- other areas of preventive medicine,

EDICAL there seems to be greater tolerance for job to go away. These data are a step in ifene-treated group represents 76% of ta- M that direction,” said Dr. Wickerham, moxifen’s chemopreventative benefit, adverse effects for effective preventative chief of the cancer genetics and preven- which translates into at 38% reduction in LOBAL interventions,” he said, noting a dis- tion section at Allegheny General Hos- invasive breast cancers,” Dr. Wickerham G crepancy between what is considered ac- pital in Pittsburgh. reported. ceptable risk for other preventative LSEVIER

The randomized, double-blind feder- In the 2006 report, raloxifene (81 /E drugs and SERMs. For example, drugs ally funded STAR trial included women events) did not appear to be as effective used to prevent hypertension and coro- at least 35 years of age with a 5-year pre- as tamoxifen (57 events) in preventing ACHTER nary artery disease have more adverse dicted breast cancer risk of at least 1.66% noninvasive breast cancer. “Now with W events and more serious events than do ERRI

(based on a modified version of the Gail additional follow-up, those differences K SERMs, he said. model). Researchers from the NSABP have narrowed,” he said. At 8 years, there “These data are good news,” Dr. D. “The adverse effects of SERMs pale in randomized 19,747 women to receive ei- was no statistical significance between Lawrence Wickerham commented. comparison to the complications of and ther tamoxifen or raloxifene (JAMA the two groups, with a risk ratio of 1.22. disability caused by breast cancer,” Dr. 2006;295:2742-51). The relative risk of 1.22 favors tamoxifen, due in part to an 80% increase in hy- Hortobagyi said. “So the challenge to- The update includes 19,490 women— but raloxifene preserves 78% of the perplasia of the endometrium that oc- day is how to communicate to the pub- 9,736 on tamoxifen and 9,754 on ralox- chemopreventative benefit of tamoxifen. curred in women on tamoxifen, Dr. lic to enhance the utilization of SERMs ifene. The differences in numbers are This translates to raloxifene preventing Wickerham said. and reduce further the incidence of due to a combination of loss during fol- 39% of noninvasive breast cancers. Both drugs increase the risk of throm- breast cancer.” ■ low-up or follow-up data becoming avail- Raloxifene maintained its toxicity ad- boembolic complications, but there were able for women who were lost to follow- vantage. The relative risk of uterine significantly fewer of these events in Disclosures: The study was supported by up in the original report. Women on cancers with raloxifene vs. tamoxifen women on raloxifene (154), compared the National Cancer Institute. Dr. tamoxifen received 20 mg/day and those was 0.55. In addition, there were twice with tamoxifen (202). Wickerham reported that he has consulted on raloxifene received 60 mg/day. as many hysterectomies for benign dis- Dr. Hortobagyi, director of the breast for Eli Lilly. Dr. Hortobagyi reported no At an average follow-up of 8 years, the ease in the tamoxifen group. This was cancer research program at the Universi- conflicts of interest. Vaccine Wins FDA Approval for Advanced Prostate Cancer

BY JANE SALODOF MACNEIL The company announced the vaccine will be avail- The pivotal Dendreon-sponsored, phase III IMPACT able initially at 50 oncology and urology centers that (Immunotherapy for Prostate Adenocarcinoma Treat- he Food and Drug Administration has approved were approved clinical trial sites. Executives said in an ment) trial randomized 512 men with metastatic cas- Tsipuleucel-T for treatment of advanced prostate investors’ call that they expected to treat the first pa- tration-resistant prostate cancer to sipuleucel-T or cancer in a much-anticipated ruling that marks the first tient within a week, and aim to serve 2,000 patients placebo. approval of a vaccine for cancer treatment. within the first 12 months. Initially, the individually tai- At a median follow-up of 3 years, the vaccine was The indication is for use in patients with “asympto- lored vaccine will be manufactured only in the com- credited with a 4.1-month gain in overall survival, with matic or minimally symptomatic prostate cancer that pany’s New Jersey facility, but Dendreon plans to add men on the vaccine living a median of 25.8 months vs. has spread to other parts of the body and is resistant facilities in Atlanta and in Orange County, Calif., by 21.7 months in the control group. to standard hormone treatment,” according to the mid-2011. Adverse events occurred in almost all patients, with FDA announcement. Sipuleucel-T will be marketed as Pricing has been set at $31,000 per infusion, or a to- chills, fatigue, fever, back pain, nausea, joint ache, and Provenge by manufacturer Dendreon. tal of $93,000 for the therapy. Executives said they plan headache being common reactions. Most side effects to meet with Medicare of- were mild or moderate, but the FDA noted that about ficials about reimburse- a quarter of patients had serious adverse reactions, in- Price Will Be an Issue for Provenge ment; about three-fourths cluding some acute infusion reactions and stroke. of the target population is “Cerebrovascular events, including hemorrhagic and fter a series of ups and downs, cally one size fits all, and there are no Medicare eligible. The ischemic strokes, were observed in 3.5% of patients in Athe much-debated prostate can- predictive tests as to which patients company also has set up a the Provenge group, compared with 2.6% of patients cer vaccine Provenge is now FDA will likely benefit from the vaccine. patient-access program to in the control group,” the agency said. approved. Instead of the end of the Coupling the financial concerns with help men who cannot af- The company announced that it has committed to discussion, the story is likely only be- Dendreon’s publicly stated manu- ford copayments. conducting “a registry of approximately 1,500 patients MY TAKE ginning. The price is said facturing shortfall (which The granting of the in- to further evaluate a small potential safety signal of to be in the $90,000 range will limit access), the dication follows a long cerebrovascular events.” for the treatment course launch and utilization of and tumultuous review An autologous cellular immunotherapy, sipuleucel- (three monthly injec- this new therapy will be a process in which protest- T delivers a patient’s own immune cells, extracted via tions), and that number story to follow closely in ors picketed after an FDA leukapheresis, in a vaccine designed to stimulate an im- will further stimulate talk this era of health reform. advisory committee re- mune response against prostatic acid phosphatase around “how much is it jected Dendreon’s initial (PAP), an antigen expressed in most prostate cancers. worth, for how long?” HOWARD A. BURRIS III, application for the vac- Men received three doses of the vaccine in intravenous and who should receive M.D., is chief medical cine. Early results from a injections given at about 2-week intervals. the therapy. officer and director of drug key trial designed to ad- “The availability of Provenge provides a new treat- With other high-priced therapies, development at Sarah Cannon dress issues raised by the ment option for men with advanced prostate cancer, such as bevacizumab (Avastin) or ce- Research Institute in Nashville, Tenn., panel failed to show an who currently have limited effective therapies avail- tuximab (Erbitux), the doses are de- and editor of THE ONCOLOGY improvement in progres- able,” said Dr. Karen Midthun, acting director of the livered repeatedly, and the overall REPORT, which is also published by sion-free survival, but re- FDA’s Center for Biologics Evaluation and Research, in cost only increases for those patients Elsevier. He has disclosed receiving searchers were eventually the FDA announcement. ■ who are benefiting clinically. In the honoraria from and consulting for able to demonstrate that case of Provenge, the price is basi- nine pharmaceutical companies. men lived longer when Emily Hayes of The Pink Sheet contributed to this report. treated with sipuleucel-T. The Pink Sheet and this publication are owned by Elsevier.