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    <recommendedItem id="20100101_19_428"
                     title="Blocking Serotonin in Gut Reverses Osteoporosis in Mice (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/Endocrinology/Osteoporosis/tb/18346?impressionId=1265756758649"
                     
      &lt;p&gt;Blocking serotonin production in the intestine might help restore lost bone mass, rather than just preventing further loss like most current osteoporosis treatments, an animal study suggested.&lt;/p&gt;
&lt;p&gt;Once daily treatment with a novel serotonin inhibitor prevented development of osteoporosis and also fully reversed existing low bone mass in mice, according Gerard Karsenty, MD, PhD, of Columbia University in New York City, and colleagues.&lt;/p&gt;
&lt;p&gt;These proof-of-principle findings came without any impact on serotonin levels in the brain, the researchers reported in the Feb. 7 issue of &lt;em&gt;Nature Medicine&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Just two years ago, Karsenty&apos;s group discovered that the vast majority of serotonin in the body acts to regulate bone formation.&lt;/p&gt;
&lt;p&gt;Only 5% plays the chemical&apos;s better-known role as a brain neurotransmitter. The rest comes from the gut for circulation below the blood-brain barrier which, in this regard, Karsenty called &quot;more hermetic than the Berlin Wall was.&quot;&lt;/p&gt;
&lt;p&gt;So the gut treatment is unlikely to affect mood and other critical functions serotonin plays in the brain, he emphasized in an interview. But he acknowledged that much more proof is needed on the way to the clinic.&lt;/p&gt;
&lt;p&gt;The tip-off to bone effects of serum serotonin came from a group of patients with a syndrome that produced high bone mass when they were into their 60s.&lt;/p&gt;
&lt;p&gt;Usually, bone destruction outpaces formation after menopause, eventually leading to osteoporosis. But something different was happening in these patients, who never developed the condition.&lt;/p&gt;
&lt;p&gt;&quot;The only cause we could find was that it was due to a decrease in the synthesis of serotonin in the gut,&quot; Karsenty told &lt;em&gt;MedPage Today&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;After their initial experiments showed serotonin did indeed boost the pace of bone formation, the researchers found that a biotech company had already developed a compound that would reduce gut synthesis of the hormone. It had been tested in women with irritable bowel syndrome.&lt;/p&gt;
&lt;p&gt;So Karsenty&apos;s group examined its effects on bone in mice and found a dose-dependent reduction in serum serotonin.&lt;/p&gt;
&lt;p&gt;Mice that got 250 mg/kg body weight per day of this compound  --  known as LP533401, a small molecule inhibitor of Tph1, the initial enzyme in gut serotonin synthesis  --  produced 30% less serotonin than controls, without a change in brain serotonin levels.&lt;/p&gt;
&lt;p&gt;Then the researchers tested the compound on mice whose ovaries had been excised to simulate the dramatic drop-off in hormones women experience after menopause. That condition, in turn, leads to an imbalance in bone resorption versus formation.&lt;/p&gt;
&lt;p&gt;Mice given the experimental drug at doses up to 10 mg/kg, starting the day after surgery, had elevated bone resorption but maintained higher bone mass than those that got placebo. The placebo group all developed osteopenia.&lt;/p&gt;
&lt;p&gt;Treated mice had a &quot;major&quot; increase in bone formation markers, including osteoblast numbers, bone formation rate, and osteocalcin serum levels. But again, brain serotonin remained unaffected.&lt;/p&gt;
&lt;p&gt;These benefits were achieved with a modest, roughly 30% reduction in serum serotonin  --  which appeared to be the threshold beyond which skeletal response increased only marginally.&lt;/p&gt;
&lt;p&gt;Some mice were left untreated for two weeks  --  &quot;a long time for a rodent,&quot; Karsenty noted  --  to develop osteopenia. Subsequently treated with a daily 250 mg/kg dose of LP533401, they had such an increase in bone formation over four weeks that it normalized their bone mass, the researchers noted.&lt;/p&gt;
&lt;p&gt;The same thing happened when researchers began treatment even longer after surgery, six or 12 weeks, when bone loss was already severe. Bone mass rose with serotonin inhibition in the vertebrae and long bones, but without a change in bone length or width.&lt;/p&gt;
&lt;p&gt;Nor were there effects on platelets, coagulation, or the GI tract with regard to the key measures of transit, colonic mobility, and gastric emptying.&lt;/p&gt;
&lt;p&gt;Serotonin inhibition in the gut as a potential anabolic treatment for osteopenia and osteoporosis appeared to work as well as the only currently available treatment that can increase bone formation sufficiently to compensate for the increased resorption caused by menopause  --  parathyroid hormone injections.&lt;/p&gt;
&lt;p&gt;Since serum serotonin inhibitors could be given in pill form, this pathway is much more attractive, Karsenty said.&lt;/p&gt;
&lt;p&gt;The specific agent used in this trial was designed for proof-of-principle and wouldn&apos;t necessarily be what is developed for clinical use, he cautioned.&lt;/p&gt;
&lt;p&gt;&quot;Although the data presented here are promising we remain fully aware that, since rodents do not remodel bones as much as humans do, our results will have to be confirmed in other species,&quot; the researchers also warned in the paper.&lt;/p&gt;
&lt;p&gt;Karsenty said the group plans to continue animal model studies for the time being, with no plans to move into clinical trials.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by grants from the National Institutes of Health and a Gideon and Sevgi Rodan fellowship from the International Bone and Mineral Society.&lt;/p&gt;&lt;p&gt;The researchers reported no conflicts of interest or industry involvement in the study.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_345"
                     title="FDA Okays Drug Combo for Advanced Breast Cancer"
                     score="0.009"
                     href="http://www.medpagetoday.com/ProductAlert/Prescriptions/tb/18224?impressionId=1265756758649"
                     
      &lt;p&gt;The FDA has approved a combination of lapatinib (Tykerb) and letrozole (Femara) to treat hormone-positive and HER2-positive advanced breast cancer in postmenopausal women.&lt;/p&gt;
&lt;p&gt;The approval follows a company-sponsored study that found that women with HER2-positive disease who were taking the combination had survival rates more than double that of women on letrozole alone (35 weeks versus 13 weeks).&lt;/p&gt;
&lt;p&gt;Lapatinib is an oral kinase inhibitor that blocks the function of the HER2-positive protein. In 2007, it was approved in combination with capecitabine (Xeloda) to treat advanced HER2-positive breast cancer tumors in refractory disease. (See &lt;a href=&quot;http://www.medpagetoday.com/HematologyOncology/Chemotherapy/5247&quot; mce_href=&quot;http://www.medpagetoday.com/HematologyOncology/Chemotherapy/5247&quot; target=&quot;_blank&quot;&gt;FDA Okays Lapatinib (Tykerb) for Treatment-Resistant Breast Cancer&lt;/a&gt;).&lt;/p&gt;
&lt;p&gt;The FDA said the most commonly reported side effects of the lapatinib/letrozole combination were diarrhea, rash, nausea, and fatigue.&lt;/p&gt;
&lt;p&gt;Treatment with lapatinib has also been associated with decreased heart function, liver damage, and inflammation of lung tissue, the agency cautioned. It may also cause harm to the fetus if used in pregnant women.&lt;/p&gt;
&lt;p&gt;Richard Pazdur, MD, director of the FDA&apos;s office of oncology drug products, said in a prepared statement that the combination &quot;provides women being treated for advanced breast cancer with an important treatment option.&quot;&lt;/p&gt;
&lt;p&gt;Lapatinib is marketed by GlaxoSmithKline and letrozole by Novartis AG.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_376"
                     title="Stress of Prostate Cancer Diagnosis May Be Deadly (CME/CE)"
                     score="0.009"
                     href="http://www.medpagetoday.com/HematologyOncology/ProstateCancer/tb/18268?impressionId=1265756758649"
                     
      Men have a slightly, but statistically significant, increased risk of dying from cardiovascular disease in the year after learning they have prostate cancer, researchers found.&lt;br&gt;
&lt;br&gt;The risk was greatest in the first month after diagnosis (standardized mortality ratio 2.05, 95% CI 1.89 to 2.22), Lorelei Mucci, PhD, of Brigham and Women&apos;s Hospital in Boston, and colleagues reported online in the &lt;em&gt;Journal of the National Cancer Institute&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;The study, which covered diagnoses made from 1979 through 2004, also found an overall increased risk of suicide in the year following a prostate cancer diagnosis (SMR 1.4, 95% CI 1.2 to 1.6), although the association was not significant after screening for prostate specific antigen (PSA) became widespread.&lt;br&gt;
&lt;br&gt;The findings&lt;em&gt;&lt;/em&gt; are &quot;one additional piece in weighing the pros and cons of PSA screening,&quot; Mucci said in an interview.&lt;br&gt;
&lt;br&gt;She also said that, &quot;not only do [clinicians] need to be treating the cancer, but they need to be thinking about the social support and other support that men may need to deal with this stressful event.&quot;&lt;p&gt;&lt;/p&gt;
&lt;p&gt;A previous study by Mucci&apos;s group that looked at a Swedish population found similarly increased risks of suicide and cardiovascular death following a prostate cancer diagnosis.&lt;/p&gt;
&lt;p&gt;Because PSA testing is more extensive in the U.S., increasing the number of early-stage and indolent cancers detected, the researchers wanted to see whether the results would carry over.&lt;/p&gt;
&lt;p&gt;Using the Surveillance, Epidemiology, and End Results (SEER) Program, they looked at data from 342,497 men who were diagnosed with prostate cancer from 1979 through 2004.&lt;/p&gt;
&lt;p&gt;The number of diagnoses steadily increased throughout the study period  --  from 6,106 in 1979 to 17,688 in 2004.&lt;/p&gt;
&lt;p&gt;But the percentage of cancers that were metastatic dropped from 18.2% in the pre-PSA period (1979 to 1986) to 5% in the period of widespread testing (1993 to 2004).&lt;/p&gt;
&lt;p&gt;During the study, 148 men committed suicide within one year of learning their diagnosis, higher than the 105.2 that would be expected in the general U.S. male population.&lt;/p&gt;
&lt;p&gt;The elevated risk was only evident prior to 1993, when PSA testing became more widely used. The authors suggested that this was likely because of the potentially lower degree of stress associated with the diagnosis of indolent prostate cancer.&lt;/p&gt;
&lt;p&gt;&quot;So that&apos;s reassuring,&quot; Mucci said.&lt;/p&gt;
&lt;p&gt;However, another 6,845 men died of cardiovascular disease, which was also higher than the expected 6,282.9.&lt;/p&gt;
&lt;p&gt;Contrary to the findings regarding suicide, the risk of cardiovascular death in the first month after hearing a diagnosis was significantly increased throughout the study period.&lt;/p&gt;
&lt;p&gt;Prostate cancer patients who were not married at the time of diagnosis had higher relative risks of both suicide and cardiovascular death than married patients.The authors suggested that this may be because &quot;having someone close to confide in might alleviate the psychological stress experienced from receiving a cancer diagnosis.&quot;&lt;/p&gt;
&lt;p&gt;They also observed a clear trend between higher relative risks for suicide and cardiovascular death among patients diagnosed with a metastatic tumor, which clearly would be more stressful than diagnosis of a clinically localized tumor.&lt;/p&gt;
&lt;p&gt;&quot;This finding might further explain the decreasing excess risks that have been observed in the PSA era, in which the proportion of advanced tumors was small (i.e., 18.2% metastatic tumors in the pre-PSA era and 5.0% in the PSA era),&quot; they wrote.&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;Risk of cardiovascular death was magnified for patients with metastatic tumors (SMR 3.22, 95% CI 2.68 to 3.84) compared with those with local or regional tumors (SMR 1.57, 95% CI 1.42 to 1.74)(&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Prostate cancer patients who were not married at the time of diagnosis had higher relative risks of both suicide and cardiovascular death than married patients.&lt;/p&gt;
&lt;p&gt;The authors acknowledged some limitations of the study, including the lack of a cancer-free group as reference and the lack of information on physical or mental health status, other prevalent disorders or comorbid illness at diagnosis, and prostate cancer treatment.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study received funding from the Swedish Council for Working Life and Social Research.&lt;/p&gt;&lt;p&gt;The authors reported no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_364"
                     title="ADT for Prostate Cancer Raises Heart Risks"
                     score="0.009"
                     href="http://www.medpagetoday.com/Urology/ProstateCancer/tb/18250?impressionId=1265756758649"
                     
      &lt;p&gt;Androgen deprivation therapy (ADT) for prostate cancer can exacerbate cardiac risk factors and may increase the risk of heart attack and cardiac death, according to an advisory supported by four medical organizations.&lt;/p&gt;
&lt;p&gt;However, the groups did not offer specific guidelines for clinicians on when to employ ADT therapy or avoid it.&lt;/p&gt;
&lt;p&gt;Clinical trials have shown that ADT increases body weight, decreases lean mass and increases fat mass, reduces insulin sensitivity, and triggers or worsens dyslipidemia.&lt;/p&gt;
&lt;p&gt;Several studies have demonstrated a significant increase in cardiovascular death in prostate cancer patients treated with hormonal therapy or bilateral orchiectomy, although some studies have shown no association between ADT and increased cardiovascular risk, according to a report that will appear in the Feb. 16 issue of &lt;em&gt;Circulation: Journal of the American Heart Association&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Some evidence also suggests ADT may predispose men to metabolic syndrome.&lt;/p&gt;
&lt;p&gt;&quot;Based on current data, it was appropriate to conclude that there may be a relationship between ADT therapy in patients with prostate cancer and future cardiovascular risk,&quot; Glenn N. Levine, MD, of Baylor College of Medicine in Houston and chair of the advisory writing committee, said in a statement.&lt;/p&gt;
&lt;p&gt;The writing committee comprised representatives of the American Heart Association, American Urological Association, and American Cancer Society. Additionally, the American Society for Radiation Oncology endorsed the advisory.&lt;/p&gt;
&lt;p&gt;The authors&apos; review of literature showed that ADT increased cardiovascular risk in 1% to 6% of various studies&apos; patient populations. With that in mind, &quot;the decision about whether to initiate ADT should be based on weighing the benefits of therapy with this potential modest risk,&quot; Levine said.&lt;/p&gt;
&lt;p&gt;The decision to initiate ADT should remain with the physician who has responsibility for treating a patient with prostate cancer, the authors wrote. That includes patients with known cardiac disease.&lt;/p&gt;
&lt;p&gt;&quot;It is the consensus of the writing group that there is no clear indication for patients for whom ADT is believed to be beneficial to be referred to internists, endocrinologists, or cardiologists for evaluation before initiation of ADT,&quot; the authors said.&lt;/p&gt;
&lt;p&gt;&quot;The decision as to whether or not to initiate ADT in patients with cardiac disease, in whom the benefits of therapy would be weighed against any possible risks, is most appropriately made by the physician treating the patient for prostate cancer.&quot;&lt;/p&gt;
&lt;p&gt;However, the potential adverse metabolic effects warrant periodic evaluation by a patient&apos;s primary care physician, they added.&lt;/p&gt;
&lt;p&gt;Noting a lack of clinical guidance for follow-up of patients treated with ADT, the advisory authors concluded that at least an annual assessment of blood glucose and lipids seems reasonable. They also called for prospective assessment of cardiovascular risk factors before and after ADT is begun in future clinical trials.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_336"
                     title="In Prostate CA, Sexual Decline After Radiation Has Limit (CME/CE)"
                     score="0.005"
                     href="http://www.medpagetoday.com/HematologyOncology/ProstateCancer/tb/18214?impressionId=1265756758649"
                     
      &lt;p&gt;Sexual function declines in the first two years after external beam radiation therapy for prostate cancer but stabilizes thereafter, according to data from a prospective cohort study.&lt;/p&gt;
&lt;p&gt;All parameters of sexual function declined significantly (&lt;em&gt;P&lt;/em&gt;&lt;0.05) in the first two years after external-beam radiation therapy (EBRT), Richard Valicenti, MD, of the University of California Davis, and colleagues found.&lt;/p&gt;
&lt;p&gt;But for years two through six of follow-up, none of the evaluated parameters of sexual function changed significantly.&lt;/p&gt;
&lt;p&gt;Pretreatment sexual function was the strongest predictor of sexual function at any time after EBRT, the investigators reported in the January issue of the &lt;em&gt;International Journal of Radiation Oncology*Biology*Physics&lt;/em&gt;&lt;em&gt;&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Their findings debunk the perception that sexual function declines continually after radiation therapy for prostate cancer.&lt;/p&gt;
&lt;p&gt;&quot;The results of this study allow patients and their partners to have a fuller understanding of the long-term sexual side effects of EBRT, and what they can expect after treatment should aid in deciding on a treatment course,&quot; Valicenti said in a statement.&lt;/p&gt;
&lt;p&gt;Reported rates of impotency after EBRT for prostate cancer have ranged from 8% to 85%, a variation the authors attributed to the different instruments used to assess sexual function. Moreover, many studies included men who received androgen deprivation therapy in addition to EBRT, possibly masking the contributions of radiation therapy to changes in sexual function.&lt;/p&gt;
&lt;p&gt;Several recent studies have suggested that rates of sexual dysfunction increase with follow-up. However, few studies included pretreatment assessment of sexual function or conducted serial assessments of sexual function after EBRT, the authors wrote.&lt;/p&gt;
&lt;p&gt;To shed more light on the question, the investigators prospectively followed 143 men who completed a sexual function questionnaire prior to EBRT for prostate cancer and at each follow-up visit. The questionnaire assessed four domains of sexual function: sexual drive, erectile function, ejaculatory function, and overall satisfaction.&lt;/p&gt;
&lt;p&gt;The mean age of the patients was 69, median Gleason score was 6, and median total radiation dose was 73.8 Gy (range of 66.6 to 79.2 Gy).&lt;/p&gt;
&lt;p&gt;During a median four-years of follow-up, the study participants completed a total of 1,187 questionnaires. Some patients were followed for as long as eight years after EBRT.&lt;/p&gt;
&lt;p&gt;Baseline scores for sexual drive and erectile function were significantly associated with patient age (&lt;em&gt;P&lt;/em&gt;=0.003 and &lt;em&gt;P&lt;/em&gt;=0.004, respectively). Ejaculatory function was significantly associated with age, race, and marital status (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05).&lt;/p&gt;
&lt;p&gt;Scores on all four domains of sexual function, as well as the total score, declined significantly in the first two years after EBRT (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05) compared with baseline values.&lt;/p&gt;
&lt;p&gt;Investigators grouped the patients according to baseline sexual function. Analysis of scores for patients above and below the median sexual function value showed that differences in sexual function persisted over time. Regression analysis showed that baseline score was the best predictor of later scores for all of the domains assessed (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;A separate analysis of scores from years two through six showed no significant changes in any of the domains: sexual drive, &lt;em&gt;P&lt;/em&gt;=0.067; erectile function, &lt;em&gt;P&lt;/em&gt;=0.5; ejaculatory function, &lt;em&gt;P&lt;/em&gt;=0.6; and overall satisfaction, &lt;em&gt;P&lt;/em&gt;=0.44.&lt;/p&gt;
&lt;p&gt;Baseline scores indicated that 74.1% of the study participants were sexually potent before EBRT. Among those who were potent before treatment, 74.4% remained potent at one year and 70.4% at two years after EBRT. The one- and two-year potency rates differed significantly from baseline, but the investigators found no statistically significant change in potency from years two through six.&lt;/p&gt;
&lt;p&gt;&quot;Our data have indicated that the widely held opinion that sexual function has a slow, progressive decline after EBRT might be incorrect,&quot; the authors wrote in conclusion. &quot;Most sexual function decline in men undergoing EBRT for prostate cancer occurred in the first two years after treatment and all domains of sexual function, including erectile dysfunction, then appeared to stabilize.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The authors reported no relevant disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
</recommendedContent>