PrimeCuts: This Week in the Journals

May 18, 2009

angeloak3.JPGMarsha Laufer MD

Faculty Peer Reviewed

“Disruption, Disruption, Disruption.” This was the title of the plenary session at last week’s SGIM meeting in Miami, Florida. What does this mean? What image does this conjure up for you in relation to Medicine? In relation to health care delivery? I think of disruption negatively and walked into the talk skeptical, but walked out feeling the opposite. Disrupt equals Change. To change the way we currently do things was the theme of the talk , truly perfectly timed to the current state of health care reform. In last week’s NEJM, John Iglehart published a perspective piece entitled “Building Momentum as Democrats Forge Health Care Reform.” In it, he described the May 11th meeting with the president where the nation’s major medical organizations committed to a goal of health care savings of nearly $2 trillion dollars in the next decade. Obama called it “a historic day.” While the details of what will be ultimate proposal for health care reform remain under-wraps, what is clear is that “disruption” will indeed occur.

Medical literature this week offered good news for the young and the old alike.

Bet this is a question you’ve never been asked: What is envenomation and how is it treated?
Medical care of children with scorpion bites, who constitute the majority of severe envenomation cases, is about to undergo a paradigm shift after a trial conducted at two U.S. hospitals and published in May 14th issue of NEJM (Boyer et al. 2009) showed the efficacy of a new preparation of antivenom in preventing scorpion sting neurotoxicity. In this study 15 children admitted to the ICU with systemic neuromotor symptoms after scorpion envenomation were randomized to receive either the specific scorpion F(ab’)2 antivenom or a placebo, in addition to standard supportive care. Four hours after the initiation of treatment the clinical syndrome resolved in 100% of children receiving antivenom vs. 14% of the placebo recipients. No children developed serum sickness, which occurred in up to 61% of the cases using the old goat-derived whole IgG preparation initially introduced by University of Arizona in 1965. Despite the limited size of this study, the safety record of the new preparation appears much improved over the old thus helping it gain acceptance among the experts in the field.

On the other end of the age spectrum, several groups reported their findings this week on a disease with a disproportional effect on the aging population; cancer.  Concato et el. found that the presence of certain molecular markers in prostate cancer biopsy samples may correlate with an increased risk of death. The authors analyzed tissue samples from 1007 U.S. veterans diagnosed with prostate cancer from 1991 to 1995 and followed until 2006. They found that immunohistochemical staining for two markers of cell cycle regulation, bcl2 and p53, as well as increased microvessel density had a small but statistically significant association with death from prostate cancer. Although usually an indolent disease when detected early, some patients with prostate cancer will be confronted with very aggressive tumors. At this time, there are limited prognostic markers available to identify those at highest risk of aggressive tumors at the time of diagnosis. Therefore, attempts at combining molecular analysis with relevant clinical endpoints are important in order to better risk-stratify prostate cancer patients and custom-tailor their therapy. Is this ready for prime time? The simple answer is: no. This study is unlikely to influence clinical practice as the reported hazard ratios are of insignificant magnitude and the associations found in this sample of fairly advanced prostate cancers may not be applicable to early prostate cancer where such prognostic information would be useful(Gelmann et al. 2009).

With a specific focus on older women with breast cancer, the results of the Cancer and Leukemia Group B (CALGB) 49907 trial, reported by Muss et el in the May 14th issue of NEJM (Muss et al. 2009) show that the standard adjuvant chemotherapy regimen should be used in this sub-population. Although chemotherapy has been the mainstay of breast cancer treatment for many years, many physicians have shied away from such aggressive approach in older patients fearing excessive toxicity. This study was designed specifically to compare the efficacy of standard chemotherapy (either cyclophosphamide, methotrexate, and fluorouracil [CMF] or doxorubicin plus cyclophosphamide) with a gentler oral fluorouracil prodrug, capecitabine, in women with early-stage breast cancer who were 65 years of age or older. In 600 women enrolled in this study, at a median follow-up of 2.4 years the relapse rate was 20% in the capecitabine group versus 11% in the standard-chemotherapy group, and the overall survival rate was 88% versus 93%. Although patients receiving standard chemotherapy were twice as likely as those receiving capcetapine to have moderate-to-severe toxicity (64% vs 33%), two treatment-related deaths in this study were in the capcetabine group. These data confirm that standard chemotherapy regimens improve survival in the older patients with breast cancer.

A randomized placebo-controlled study of lifestyle interventions in overweight elderly cancer survivors published in the May 13th issue of JAMA (Morey et al. 2009) shows that telephone counseling and printed material on diet and exercise are effective approaches to improve physical function and the quality of life in this group of patients. At the 12-month follow-up self-reported physical function score declined less rapidly in the intervention group (-2.15) compared with the control group (-4.84) (P = .03). Not only did the overall quality of life improve significantly in the intervention group compared with the control, but there was also an objective measure of efficacy as the intervention group attained a greater degree of weight loss (2.06 kg vs 0.92 kg). An important aspect of this study for the general practitioner is that older long-term survivors of breast, prostate and colorectal cancers under your care my be able to successfully implement lifestyle modification changes and will derive benefits from them.

Dr. Laufer is a first year resident in internal medicine at NYU Medical Center.

Reviewed by Judith Brenner MD, Associate Editor, Clinical Correlations

References:

Boyer LV et al. Antivenom for critically ill children with neurotoxicity from scorpion stings. N Engl J Med 2009; 360 (20):2090-8.

Concato J et al. Molecular markers and death from prostate cancer. Ann Intern Med 2009; 150 (9):595-603.

Gelmann EP, Henshall SM. Clinically relevant prognostic markers for prostate cancer: the search goes on. Ann Intern Med 2009; 150 (9):647-9.

Morey MC et al. Effects of home-based diet and exercise on functional outcomes among older, overweight long-term cancer survivors: RENEW: a randomized controlled trial. Jama 2009; 301 (18):1883-91.

Muss HB et al. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med 2009; 360 (20):2055-65.

Inglehart, JK. Building Momentum as Democrats Forge Health Care Reform. N Engl J Med 2009; 360 (20): online only.

 

 

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