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    <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=1265739523012"
                     
      &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_342"
                     title="Stem Cell Transplant Source Does Not Affect Long-Term Leukemia Outcomes (CME/CE)"
                     score="0.009"
                     href="http://www.medpagetoday.com/HematologyOncology/Leukemia/tb/18220?impressionId=1265739523012"
                     
      Ten-year survival rates after allogeneic stem-cell transplant in leukemia patients were the same whether the cells came from donors&apos; bone marrow or peripheral blood, researchers conducting a randomized trial said.&lt;br&gt;
&lt;br&gt;Among 329 patients participating in the trial, overall survival was 49.1% for those receiving peripheral blood progenitor cell transplants versus 56.5% among those receiving bone marrow transplants (&lt;em&gt;P&lt;/em&gt;=0.27), reported Birte Friedrichs, MD, of Charite-Campus Benjamin Franklin in Berlin, Germany, and colleagues online in &lt;em&gt;Lancet Oncology&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;There was also no significant difference over the long term in performance status, ability to work, hematopoietic function, development of bronchiolitis obliterans, or secondary malignancy rates.&lt;/p&gt;
&lt;p&gt;Ten-year leukemia-free survival rates were somewhat better with bone marrow transplant in patients with acute myeloid and acute lymphoblastic leukemia (AML, ALL) but the differences did not reach statistical significance. There was no apparent difference in disease-free survival for those with chronic myeloid leukemia (CML).&lt;/p&gt;
&lt;p&gt;But significantly more transplants involving peripheral blood progenitor cells led to chronic graft-versus-host disease (GVHD), seen in 73% of patients compared with 56% among those receiving bone marrow transplants (&lt;em&gt;P&lt;/em&gt;=0.021).&lt;/p&gt;
&lt;p&gt;As a result, significantly more patients receiving peripheral blood cell transplants were on immunosuppressant therapy five years postprocedure (26% versus 12%, &lt;em&gt;P&lt;/em&gt;=0.024).&lt;/p&gt;
&lt;p&gt;Noting that subgroup analyses did show notable differences in survival in patients with acute leukemias, Friedrichs and colleagues added, &quot;These data alone do not currently support the return to bone marrow transplantation for specific indications, but we believe that long-term data from other randomized trials should be collected.&quot;&lt;/p&gt;
&lt;p&gt;Patients in the study were participating in a parallel-group trial of the two transplant types, with transplants conducted from 1995 to 1999. Participants were adults up to age 55 with CML in second remission or newly diagnosed ALL or AML.&lt;/p&gt;
&lt;p&gt;Specific overall and leukemia-free survival rates for leukemia subtypes after 10 years were: &lt;ul&gt; &lt;li&gt;ALL: 32.9% overall and 28.3% disease-free with bone marrow transplant, 18.2% overall and 13.0% disease free with peripheral blood transplant (&lt;em&gt;P&lt;/em&gt;=0.071 and 0.12, respectively)&lt;/li&gt; &lt;li&gt;AML: 65.3% overall and 62.3% disease-free with bone marrow transplant, 52.3% overall and 47.1% disease-free with peripheral blood transplant (&lt;em&gt;P&lt;/em&gt;=0.24 and 0.16, respectively)&lt;/li&gt; &lt;li&gt;CML: 61.1% overall and 40.2% disease-free with bone marrow transplant, 56.8% overall and 48.5% disease-free with peripheral blood transplant (&lt;em&gt;P&lt;/em&gt;=0.81 and 0.60, respectively)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The failure to find significant differences may have been related to small patient numbers in these subgroups: 64 with AML, 19 with ALL, and 89 with CML.&lt;/p&gt;
&lt;p&gt;Transplant types were performed at equal rates in patients with AML and CML, but the randomization was unbalanced in ALL patients, with 15 of 19 receiving bone marrow transplants.&lt;/p&gt;
&lt;p&gt;Chronic GVHD was the most common cause of death in the study, killing nine patients (of whom six received peripheral blood progenitor cell transplants). Six patients died of recurrent leukemia. The remaining nine deaths were distributed among several causes including hemorrhage, bronchial cancer, suicide, and traffic accident.&lt;/p&gt;
&lt;p&gt;Patients with chronic GVHD after peripheral blood cell transplants were more likely to have skin, liver, and oral mucosal involvement compared with GVHD following bone marrow transplant, with relative risks ranging from 1.49 to 1.85.&lt;/p&gt;
&lt;p&gt;Factors significantly associated with better overall survival included a diagnosis of ALL (HR 2.90 versus other diagnoses, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001), age of 40 or more (HR 1.55 versus age under 40, &lt;em&gt;P&lt;/em&gt;=0.009), and use of total body irradiation instead of a chemotherapy-only myeloablative regimen before transplant (HR 1.55, &lt;em&gt;P&lt;/em&gt;=0.014).&lt;/p&gt;
&lt;p&gt;The researchers noted that many of their findings, including the apparent benefit of preparative total body irradiation, were consistent with earlier studies.&lt;/p&gt;
&lt;p&gt;Limitations to the study included loss to follow-up of 26 patients, lack of detailed data on surviving participants&apos; quality of life, and changes in treatment since the study began.&lt;/p&gt;
&lt;p&gt;Friedrichs and colleagues noted that the introduction of tyrosine kinase inhibitors and new approaches to pretransplant conditioning have altered practice significantly.&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;No external funding for the study was received.&lt;/p&gt;&lt;p&gt;No potential conflicts of interest were reported.&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="0.005"
                     href="http://www.medpagetoday.com/ProductAlert/DevicesandVaccines/tb/18158?impressionId=1265739523012"
                     
      &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="20100101_19_167"
                     title="Stem Cells from Cord Blood Pass Early Test (CME/CE)"
                     score="-0.004"
                     href="http://www.medpagetoday.com/HematologyOncology/Leukemia/tb/17998?impressionId=1265739523012"
                     
      The first reported clinical use of ex vivo-expanded stem cells from umbilical cord blood led to rapid engraftment in patients with high-risk acute leukemia, investigators found.&lt;br&gt;
&lt;br&gt;Activation of the Notch signaling pathway with a bioengineered protein led to a 164-fold increase in CD34+ cells. Infusion of the expanded stem-cell population into leukemia patients after myeloablation reduced the time to neutrophil recovery and the time to engraftment by 50%, according to a report published online in &lt;em&gt;Nature Medicine&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;After a mean follow-up of about a year, seven of 10 patients remained alive with no evidence of disease and with sustained complete engraftment, wrote Colleen Delaney, MD, of the Fred Hutchinson Cancer Research Center in Seattle, and colleagues.&lt;br&gt;
&lt;br&gt;&quot;The real ground-breaking aspect of this research is that we have shown that you can manipulate stem/progenitor cells in the lab with the goal of increasing their numbers,&quot; Delaney said in a statement.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;&quot;When given to a person, these cells can rapidly give rise to white blood cells and other components of the blood system.&quot;&lt;/p&gt;
&lt;p&gt;Delayed engraftment after cord-blood transplantation is thought to result from an inadequate population of progenitor cells in the graft, the authors wrote. Delayed engraftment can lead to early transplant-related morbidity and mortality.&lt;/p&gt;
&lt;p&gt;Culture strategies that increase the number of viable progenitors would expand the applicability of cord-blood for transplantation.&lt;/p&gt;
&lt;p&gt;The phase I results reported by Delaney and colleagues had their origin in work begun more than a decade ago by co-investigator Irwin D. Bernstein, also of Fred Hutchinson. The Seattle group identified a potential role for the Notch signaling pathway in hematopoiesis by detecting the human &lt;em&gt;Notch 1&lt;/em&gt; gene in CD34+ human hematopoietic precursors. They subsequently demonstrated enhanced self-renewal of repopulating cells in response to retrovirus-mediated expression of an active form of Notch 1.&lt;/p&gt;
&lt;p&gt;Further study showed that activation of Notch receptors by immobilized Notch ligand had a profound effect on growth and differentiation of mouse marrow progenitor cells. Incubation of human cord-blood progenitors with immobilized ligand led to a 100-fold increase in CD34+ cells.&lt;/p&gt;
&lt;p&gt;&quot;Overall, these observations demonstrated that Notch signaling has a key regulatory role in hematopoiesis and suggest that Notch ligands will be useful reagents for improving ex vivo culture of stem/progenitor cells,&quot; the authors wrote.&lt;/p&gt;
&lt;p&gt;As a prelude to the phase I clinical study, investigators cultured cord-blood CD34+ progenitors in the presence of immobilized Notch ligand for as long as three weeks, resulting in 138- to 163-fold expansion of the cell population. Validation studies of the culture system showed consistent expansion of the CD34+ population by more than 150-fold.&lt;/p&gt;
&lt;p&gt;When given to immunodeficient mice, ex vivo-expanded CD34+ cells resulted in repopulation with markedly enhanced kinetics and magnitude.&lt;/p&gt;
&lt;p&gt;The phase I study involved patients whose leukemia was in morphologic remission at the time of transplant. The patients ranged in age from 3 to 43.&lt;/p&gt;
&lt;p&gt;Myeloablative therapy consisted of whole-body irradiation, cyclophosphamide, and fludarabine. Each patient received one unmanipulated and one expanded cord-blood graft. All patients received standard prophylaxis for graft versus host disease (GVHD). Expansion of CD34+ cells prior to infusion averaged 164-fold.&lt;/p&gt;
&lt;p&gt;The median time to an absolute neutrophil count (ANC) &amp;#8805;100 cells/&amp;#181;L was nine days, compared with 19 days for a similar group of patients who received two unmanipulated cord-blood grafts.&lt;/p&gt;
&lt;p&gt;The median time to ANC &amp;#8805;500 cells/&amp;#181;L was 16 days in nine evaluable patients, compared with 26 days in patients who received two unmanipulated grafts.&lt;/p&gt;
&lt;p&gt;Nine of 10 patients had successful engraftment in an average of 14 days, whereas engraftment required an average of 28 days in patients who received unmanipulated cord-blood grafts.&lt;/p&gt;
&lt;p&gt;One patient had primary graft rejection. Peripheral blood analysis on day seven showed a predominance of donor-cell engraftment from the expanded-cell graft.&lt;/p&gt;
&lt;p&gt;Among evaluable patients, one had acute grade 3 GVHD, and all the others had acute grade 2 GVHD. In all cases patients responded to therapy. Three patients developed chronic limited GVHD, but no patient had chronic extensive GVHD.&lt;/p&gt;

&lt;p&gt;Results of the phase I study give reason for excitement about the potential for using cord blood-derived stem cells to treat leukemia, said Peter Emanuel, MD, director of the Winthrop P. Rockefeller Cancer Institute in Little Rock, Ark.&lt;/p&gt;
&lt;p&gt;&quot;Investigators from [Seattle] appear to have given us the next big leap forward in advances for stem cell transplants, that being the methods to culture cord blood in the laboratory so that the stem and immature cells will &apos;take root&apos; more rapidly when infused back into patients,&quot; said Emanuel, who was not involved in the study. &quot;This is significant for patient safety as it shortens the time period when they are at risk for life threatening infection.&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 had no disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_2766"
                     title="FDA Panel: More Data Needed for Two Cancer Drugs"
                     score="-0.005"
                     href="http://www.medpagetoday.com/HematologyOncology/Leukemia/tb/15802?impressionId=1265739523012"
                     
      &lt;p&gt;WASHINGTON  --  An FDA advisory panel recommended that randomized, controlled trials be required before the agency approves two drugs to treat acute myeloid leukemia, clofarabine (Clolar) and laromustine (Onrigin).&lt;/p&gt;
&lt;p&gt;The Oncologic Drugs Advisory Committee voted 9 to 3 Tuesday morning to recommend that Genzyme, the makers of clofarabine, conduct a controlled trial before the FDA approves the drug to treat acute myeloid leukemia (AML) in older patients.&lt;/p&gt;
&lt;p&gt;That afternoon, it voted the same way on an application from Vion Pharmaceuticals, which wanted approval for its investigational drug, laromustine (Onrigin) for the same indication.&lt;/p&gt;
&lt;p&gt;Genzyme was seeking approval to market clofarabine to treat the blood cell cancer in patients 60 and older who have at least one unfavorable baseline prognostic factor, which would make them unlikely to respond to standard induction or their intensive chemotherapy.&lt;/p&gt;
&lt;p&gt;In documents released before the advisory meeting, FDA staff was critical of the data Genzyme submitted and said the company acted against the agency&apos;s guidance when it failed to perform a randomized, controlled trial of clofarabine against a placebo. Instead, Genzyme relied mainly on data from a single-arm, phase II study with 116 patients to support its bid.&lt;/p&gt;
&lt;p&gt;The panel was also concerned that a substantial number of patients in that study, 25% to 41%, may have been candidates for standard induction chemotherapy or other intensive chemotherapy.&lt;/p&gt;
&lt;p&gt;The FDA review also pointed out that the committee had voted down the only previous application for an AML drug in elderly patients that was backed only by uncontrolled studies.&lt;/p&gt;
&lt;p&gt;In that 2005 action involving tipifarnib (Zarnestra), the advisory panel voted 7 to 4 against approval, and the FDA, as usual, followed the committee&apos;s advice.&lt;/p&gt;
&lt;p&gt;Clofarabine is currently approved for treating acute lymphoblastic leukemia in patients up to age 21.&lt;/p&gt;
&lt;p&gt;Following the tone of the earlier vote, the panel recommended  --  this time unanimously  --  that the data on laromustine lacked a crucial controlled, randomized study and that its maker, Vion Pharmaceuticals, would have to conduct one to gain approval.&lt;/p&gt;
&lt;p&gt;The background studies that Vion cited in its application were single-arm, and patients had a 28% to 29% remission rate. But those results may have been confounded by the use of additional drugs, the FDA said.&lt;/p&gt;
&lt;p&gt;Also, FDA staff noted toxicities discovered in that trial, including increased mortality when the drug was combined with cytarabine.&lt;/p&gt;
&lt;p&gt;One panel member said he wondered why laromustine was being used in the first place.&lt;/p&gt;
&lt;p&gt;&quot;There&apos;s an increased risk of pulmonary problems,&quot; said Ronald Richardson, MD, a medical oncologist at the Mayo Clinic. &quot;If it&apos;s going to have role, it should be on the basis of adequate data looking at a randomized, controlled study.&quot;&lt;/p&gt;
&lt;p&gt;On Wednesday, the panel was scheduled to discuss two other cancer drugs: romidepsin (Istodax) for cutaneous T-cell lymphoma, and pralatrexate (Folotyn) for peripheral T-cell lymphoma.&lt;/p&gt;

    </recommendedItem>
</recommendedContent>
