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    <recommendedItem id="20100101_19_345"
                     title="FDA Okays Drug Combo for Advanced Breast Cancer"
                     score="0.008"
                     href="http://www.medpagetoday.com/ProductAlert/Prescriptions/tb/18224?impressionId=1265814190078"
                     
      &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_330"
                     title="Immune Cells Point to Skin Cancer Risk after Transplants (CME/CE)"
                     score="0.005"
                     href="http://www.medpagetoday.com/Nephrology/KidneyTransplantation/tb/18200?impressionId=1265814190078"
                     
      Monitoring two types of immune cells in kidney transplant recipients might identify patients with an increased risk of skin cancer, British investigators reported.&lt;br&gt;
&lt;br&gt;Increased levels of T-regulatory cells (Tregs) more than doubled the risk of squamous cell cancer of the skin. Decreased levels of natural killer (NK) cells were associated with more than a five-fold increased risk of skin cancer.&lt;br&gt;
&lt;br&gt;Both immune parameters had substantially greater predictive power than a history of squamous-cell skin cancer, according to an online report in the &lt;em&gt;Journal of the American Society of Nephrology&lt;/em&gt; by a team of Oxford University investigators.&lt;/p&gt;
&lt;p&gt;&quot;Squamous cell cancer of the skin affects about 30% of kidney transplant patients after 10 years of immunosuppression,&quot; Robert Carroll, MD, currently of Queen Elizabeth Hospital in Woodville, Australia, observed in a statement.&lt;/p&gt;
&lt;p&gt;&quot;A small number of patients develop multiple skin cancers per year, but there is no laboratory test to determine which transplant recipients will develop multiple skin cancers in the future.&quot;&lt;/p&gt;
&lt;p&gt;&quot;If a test can confirm high risk of skin cancer development, this may help clinicians to tailor immunosuppressive regimens for individual patients,&quot; he added.&lt;/p&gt;
&lt;p&gt;Long-term immunosuppression, such as that required for transplant recipients, confers an increased risk of squamous-cell skin cancer.&lt;/p&gt;
&lt;p&gt;Estimates of the magnitude have ranged as high as 200 times greater than the general population, the authors wrote. Additionally, 3% of organ transplant recipients require extensive plastic surgery each year as a result of skin cancer lesions.&lt;/p&gt;
&lt;p&gt;Age at transplantation and the immunosuppression dosage are the principal determinants of skin-cancer risk, and the dosage of immunosuppression also influences the risk of metastasis from squamous-cell cancer of the skin.&lt;/p&gt;
&lt;p&gt;In the general population, cancer has been associated with increased levels of Tregs, including CDR&lt;sup&gt;+&lt;/sup&gt;CD25&lt;sup&gt;high&lt;/sup&gt;FOXP3&lt;sup&gt;+&lt;/sup&gt; and CD8&lt;sup&gt;+&lt;/sup&gt;CD28&lt;sup&gt;-&lt;/sup&gt; cells. The same types of cells could play a role in the risk of skin cancer among organ transplant recipients, the authors wrote.&lt;/p&gt;
&lt;p&gt;Within the tumor microenvironment, Tregs may impair the antitumor activity of CD8&lt;sup&gt;+&lt;/sup&gt; and NK cell. However, in organ transplant recipients, Tregs help control or prevent rejections and may help improve long-term outcomes.&lt;/p&gt;
&lt;p&gt;Different immunosuppressive drugs affect Tregs differently, the authors continued. Sirolimus (Rapamune), for example, increases the number of FOXP3&lt;sup&gt;+&lt;/sup&gt; cells, whereas cyclosporine decreases Treg numbers.&lt;/p&gt;
&lt;p&gt;&quot;Tregs have not been assessed in relation to cancer after transplantation,&quot; the authors wrote. &quot;We therefore investigated the hypothesis that squamous-cell cancer in kidney transplant recipients would be associated with an increased number of Tregs.&quot;&lt;/p&gt;
&lt;p&gt;To examine the hypothesis, investigators phenotyped peripheral blood from 65 kidney transplant recipients with squamous skin cancer and 51 recipients without skin cancer, matched for age, sex, and duration of immunosuppression.&lt;/p&gt;
&lt;p&gt;They also quantified lymphocyte populations in skin cancer lesions from a subset of 25 patients and matched them with 25 other nontransplant patients with squamous cell cancer of the skin.&lt;/p&gt;
&lt;p&gt;The kidney transplant recipients had a median follow-up of 340 days. The investigators found that a concentration of &amp;gt;35 peripheral FOXP3&lt;sup&gt;+&lt;/sup&gt;CD4&lt;sup&gt;+&lt;/sup&gt;CD127&lt;sup&gt;low&lt;/sup&gt; regulatory T cells/&amp;#181;L was associated with a hazard ratio for squamous cell skin cancer of 2.48 (95% CI 1.04 to 5.98).&lt;/p&gt;
&lt;p&gt;An NK cell count &amp;lt;100 cells/&amp;#181;L was associated with a skin cancer hazard ratio of 5.6 (95% CI 1.31 to 24). A history of squamous cell cancer of the skin increased the risk of skin cancer recurrence by a third (HR 1.33, 95% CI 1.15 to 1.53).&lt;/p&gt;
&lt;p&gt;&quot;If similar immune phenotypes are predictive in other kidney transplant recipient populations, then immune phenotype method has the potential to inform immunosuppressive regimen manipulation in kidney transplant recipients at high risk for developing multiple squamous cell cancers,&quot; the authors concluded.&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 had no relevant disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_298"
                     title="FDA Updates Myeloma Drug Label for New Risks"
                     score="0.002"
                     href="http://www.medpagetoday.com/ProductAlert/DevicesandVaccines/tb/18158?impressionId=1265814190078"
                     
      &lt;p&gt;WASHINGTON  --  The FDA has revised dosage and safety information for bortezomib (Velcade), the myeloma and mantle cell lymphoma drug, to reflect an increased toxicity risk.&lt;/p&gt;
&lt;p&gt;The new labeling includes a warning for patients with moderate-to-severe hepatic impairment and now recommends at-risk patients start at a lower dosage of 0.7 mg for the first cycle of treatment and escalate to 1.0 mg, or reduce further to 0.5 mg, in subsequent cycles.&lt;/p&gt;
&lt;p&gt;The label has also been updated to include clinical study data showing a higher median survival rate in patients using a combination of bortezomib, melphalan, and prednisone versus a regiment of just melphalan and prednisone (&lt;em&gt;P&lt;/em&gt;=0.00084).&lt;/p&gt;
&lt;p&gt;The drug is contraindicated in patients with hypersensitivity to bortezomib, boron, or mannitol. The FDA also warns that women should avoid becoming pregnant while undergoing treatment with bortezomib.&lt;/p&gt;
&lt;p&gt;The drug is manufactured by Millennium: The Takeda Oncology Company of Cambridge, Mass.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20090101_1_784"
                     title="New Technique Improves Efficacy of Bone Marrow Transplants"
                     score="-0.007"
                     href="