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    <recommendedItem id="20100101_19_461"
                     title="Limited Benefit Seen in CML Drug, FDA Says"
                     score="0.013"
                     href="http://www.medpagetoday.com/HematologyOncology/Leukemia/tb/18390?impressionId=1265777032194"
                     
      &lt;p&gt;WASHINGTON  --  Chronic myeloid leukemia (CML) patients who are resistant to imatinib (Gleevec) had a low response rate to treatment with omacetaxine (Omapro), according to Food and Drug Administration (FDA) reviewers.&lt;/p&gt;

&lt;p&gt;The FDA released its assessment of omacetaxine, made by ChemGenex Pharmaceuticals, in preparation for a meeting of an outside panel of oncology experts who will recommend whether the agency should approve the drug for imanitib-resistant CML patients with a Bcr-Abl T3151 mutation.&lt;/p&gt;
    &lt;p&gt;That meeting, original scheduled for Wednesday, was postponed when the federal government closed most Washington area offices because of snow. An FDA spokesman said no new date has been set.&lt;/p&gt;


&lt;p&gt;The agency does not have to follow the advice of its advisory panels, but it usually does.&lt;/p&gt;
&lt;p&gt;The Oncologic Drugs Advisory Committee will look at data from manufacturer ChemGenex&apos;s lone trial, which tested the safety and efficacy of subcutaneously administered omacetaxine in the target population.&lt;/p&gt;
&lt;p&gt;The trial divided 66 patients into disease stage cohorts of &quot;chronic phase,&quot; &quot;accelerated phase,&quot; or &quot;blast phase,&quot; and gave them 1.25 mg/m&lt;sup&gt;2&lt;/sup&gt; subcutaneous omacetaxine twice daily for 14 days every 28 days until hematologic response for induction therapy.&lt;/p&gt;
&lt;p&gt;If a patient achieved a complete hematologic response, hematologic improvement, or any cytogenetic response, the patient was transitioned to a maintenance does twice daily for seven days every 28 days.&lt;/p&gt;
&lt;p&gt;Researchers found: &lt;ul&gt; &lt;li&gt;For the chronic phase cohort of 40 patients, the major cytogenetic response rate was 15%, and the median duration of response was 7.7 months. &lt;/li&gt; &lt;li&gt;After a mean of nine months, 86% of the 49 chronic patients who were no longer controlling their diseases with imatinib had achieved a complete hematological response. &lt;/li&gt; &lt;li&gt;For the &quot;accelerated phase&quot; cohort of 16 patients, the major cytogenetic response rate was 6%, and the complete hematological response rate was 31%, with a median of duration of response of 22 weeks. &lt;/li&gt; &lt;li&gt;No patients responded in the more severe &quot;blast&quot; group, indicating omacetaxine works best among patients who are not as sick.&lt;/li&gt; &lt;li&gt;Overall, about 27% of patients achieved a major cytogenetic response, defined as absence of Bcr-Abl mutation in at least 35% of cells. About 18% of the patients had achieved a complete cytogenetic response, defined as all cells appearing to have lost the Bcr-Abl mutation.&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;&quot;The response rate observed in the efficacy study was low,&quot; FDA reviewers concluded in documents released in advance of Wednesday&apos;s meeting.&lt;/p&gt;
&lt;p&gt;However, ChemGenex researchers said, &quot;These results demonstrate that omacetaxine is an effective and durable therapy with rapid onset of action for CML patients with the Bcr-Abl T315I mutation.&quot;&lt;/p&gt;
&lt;p&gt;The most common adverse events in the trial were thrombocytopenia, anemia, diarrhea, and neutropenia.&lt;/p&gt;
&lt;p&gt;The FDA reviewers cited a number of concerns with the ChemGenex study, noting that the company planned to enroll 100 patients but submitted efficacy data from only 66, and then continued to enroll additional patients after the prespecified data cutoff.&lt;/p&gt;
&lt;p&gt;Also, the reviewers said there is no commercially available test to detect the T3151 mutation. And, although it was a requirement of the study that the patients have a confirmed T3151 mutation, the mutation status of 35% of the patients in the trial was not confirmed.&lt;/p&gt;
&lt;p&gt;There are currently no approved drugs that have been found to be effective at treating CML patients with the T315I mutation.&lt;/p&gt;
&lt;p&gt;&quot;Omacetaxine offers an important therapeutic option for the treatment of CML patients who have the T315I mutation, a population that has a clear unmet medical need and no proven treatment options,&quot; ChemGenex researchers wrote in the company&apos;s briefing document.&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=1265777032194"
                     
      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_377"
                     title="Advisory Panel Rates Genomic Cancer Tests"
                     score="0.008"
                     href="http://www.medpagetoday.com/PublicHealthPolicy/Medicare/tb/18269?impressionId=1265777032194"
                     
      &lt;p&gt;Some genomic tests aimed at identifying patients most likely to respond to cancer drugs won a thumbs-up from a Medicare advisory panel, but others didn&apos;t make the grade.&lt;/p&gt;
&lt;p&gt;As part of a national coverage determination under way at the Centers for Medicare and Medicaid Services, members of the Medicare Evidence Development &amp;amp; Coverage Advisory Committee (MEDCAC) last week rated the clinical value of several pharmacogenomic cancer tests now available.&lt;/p&gt;
&lt;p&gt;The tests would be used to select patients for treatment with drugs including tamoxifen, irinotecan (Camptosar), trastuzumab (Herceptin), and imatinib (Gleevec).&lt;/p&gt;
&lt;p&gt;CMS has not previously decided whether such tests should be reimbursed by Medicare, although testing is already routine for some of these treatments.&lt;/p&gt;
&lt;p&gt;The FDA-approved labeling for trastuzumab requires such testing. Imatinib&apos;s approvals include chronic myeloid leukemia featuring the BCR-ABL &quot;Philadelphia chromosome&quot; mutation, although the label doesn&apos;t explicitly mention testing.&lt;/p&gt;
&lt;p&gt;&quot;CMS is aware that the body of evidence on the role of pharmacogenomic testing in cancer continues to evolve,&quot; according to the agency&apos;s notice of the meeting.&lt;/p&gt;
&lt;p&gt;&quot;Recognizing the rapid accumulation of such evidence, CMS seeks guidance from the panel to inform future coverage determinations. We want to ensure that Medicare beneficiaries have access to any demonstrated improved health outcomes of pharmacogenomic testing, and are protected from inaccurate or inappropriate pharmacogenomic testing that could compromise therapy or increase the risks of adverse events during therapy.&quot;&lt;/p&gt;
&lt;p&gt;MEDCAC panelists were asked to rate their confidence in the clinical utility of five tests and in the scientific evidence available for review.&lt;/p&gt;
&lt;p&gt;The five tests cover: &lt;ul&gt; &lt;li&gt;Polymorphisms in the CYP2D6 drug-metabolizing enzyme for breast cancer patients who are candidates for tamoxifen&lt;/li&gt; &lt;li&gt;Polymorphisms in the UGT1A1 gene for colon cancer patients considered for irinotecan treatment&lt;/li&gt; &lt;li&gt;Presence of HER/neu epidermal growth factor receptor expression in patients with breast cancer, indicating suitability for trastuzumab&lt;/li&gt; &lt;li&gt;Presence of the BCR-ABL mutation in patients with chronic myeloid leukemia who would be candidates for imatinib&lt;/li&gt; &lt;li&gt;Mutations in the K-ras gene for metastatic colorectal cancer patients eligible for cetuximab (Erbitux) or panitumumab (Vectibix)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The 15 panel members assigned values of one to five, reflecting low to high confidence, to each test. A score of two reflected medium-low confidence, while a four meant medium-high confidence.&lt;/p&gt;
&lt;p&gt;Most of the panelists agreed that the evidence underlying the tests for CYP2D6 and UGT1A1 polymorphisms was still too scant for an assessment of their clinical value. Mean scores for these tests were 2.07 and 1.83, respectively, with nearly all votes either a one or two.&lt;/p&gt;
&lt;p&gt;But MEDCAC members were more confident that the usefulness of the other three tests for diagnostic and monitoring purposes could be evaluated. Mean scores for those tests were all well above four.&lt;/p&gt;
&lt;p&gt;For the HER/neu, BCR-ABL, and K-ras tests, since members believed the evidence was adequate for assessment, MEDCAC also voted on whether their use actually would improve health outcomes in cancer patients.&lt;/p&gt;
&lt;p&gt;A third ranking provided the committee&apos;s views on whether the conclusions could be generalized to the Medicare population and patients in the community.&lt;/p&gt;
&lt;p&gt;Mean scores for those rankings were all also above four, indicating the panel&apos;s support for these tests as clinically beneficial.&lt;/p&gt;
&lt;p&gt;On the other hand, when asked whether there was enough evidence to assess the utility of the BCR-ABL test in detecting treatment failure, panelists didn&apos;t think so. Most of those votes were twos, and the mean was 2.47.&lt;/p&gt;
&lt;p&gt;CMS has not given a time line for deciding whether to approve Medicare coverage for the tests.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_304"
                     title="&apos;Virtual&apos; Colon Scans Effective in Seniors (CME/CE)"
                     score="0.002"
                     href="http://www.medpagetoday.com/HematologyOncology/ColonCancer/tb/18164?impressionId=1265777032194"
                     
      Patients 65 and older are as suitable as younger individuals for CT colonography, said researchers conducting a large retrospective study.&lt;br&gt;
&lt;br&gt;Advanced neoplasias were detected with CT colonography  --  often called &quot;virtual colonoscopy&quot;  --  in older patients at more than double the rate in the general screening population, reported David H. Kim, MD, of the University of Wisconsin in Madison, Wis., and colleagues in the February issue of &lt;em&gt;Radiology&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;They found that 7.6% of older patients had advanced neoplasias, compared with 3.2% of all patients screened in the university&apos;s clinic (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;On the basis of this and other findings in 577 individuals 65 and older versus the entire group of 3,120 patients undergoing the procedure, Kim and colleagues concluded that &quot;CT colonography performance is maintained in an older cohort.&quot;&lt;/p&gt;
&lt;p&gt;&quot;Overall, the observations from this clinical experience confirm that CT colonography may be a valuable screening modality in the older population,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;On the other hand, the study did not address several objections raised by the Centers for Medicare and Medicaid Services (CMS) in its decision last year to deny Medicare coverage for the procedure. (See &lt;a href=&quot;http://www.medpagetoday.com/PublicHealthPolicy/Medicare/14186&quot; mce_href=&quot;http://www.medpagetoday.com/PublicHealthPolicy/Medicare/14186&quot; target=&quot;_blank&quot;&gt;Medicare Finalizes Denial of Virtual Colonoscopy Coverage&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;CMS had pointed to relatively low sensitivity of CT colonography compared with optical colonoscopy in prospective trials, especially for small lesions.&lt;/p&gt;
&lt;p&gt;The agency also determined that CT colonography increased the costs of positive findings, since abnormalities in the CT scans must be confirmed with optical colonoscopy. In addition, CMS said there was no evidence to support claims that the less invasive imaging procedure would be more acceptable to patients and therefore would raise screening rates.&lt;/p&gt;
&lt;p&gt;The data analyzed by Kim and colleagues did not allow for calculations of false-negative rates or predictive values of positive or negative findings. Nor did the researchers report cost information.&lt;/p&gt;
&lt;p&gt;Mean age of their older cohort was 69.2 (SD 3.8). The oldest was 79.&lt;/p&gt;
&lt;p&gt;The researchers reported that 15.3% of the older patients were referred for optical colonoscopy on the basis of the CT results, compared with 7.9% of the overall screening group.&lt;/p&gt;
&lt;p&gt;Less than 4% of positive findings were determined to be false with the optical procedure (3.6% for polyps 6 to 10 mm in diameter, 2.1% for larger lesions).&lt;/p&gt;
&lt;p&gt;Of the 59 advanced neoplasias identified in the older patients, all but three were at least 10 mm in size.&lt;/p&gt;
&lt;p&gt;The scans also suggested abnormalities outside the colon in 89 (15.4%) patients. Of these, 45 received a full workup, which revealed substantial and previously unsuspected diagnoses in 21 cases  -- 18 were vascular aneurysms. The other three included one lung tumor, a femoral hernia, and a malrotation.&lt;/p&gt;
&lt;p&gt;Kim and colleagues reported that no &quot;substantial complications&quot; such as perforations or major hemorrhage occurred in the older patients, either with the CT scan or follow-up colonoscopy.&lt;/p&gt;
&lt;p&gt;They also indicated that the ratio of large to small neoplasias was similar in the older patients compared with their CT screening group as a whole. Histologic and morphologic findings were similar as well.&lt;/p&gt;
&lt;p&gt;The researchers cited the observational nature of the study, in which negative findings were not corroborated with optical colonoscopy, and its restriction to a single center as its main limitations.&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 reported.&lt;/p&gt;&lt;p&gt;Kim and one co-author reported relationships with Viatronix and Medicsight and are co-founders of a company called VirtuoCTC, which produces educational materials on CT colonography.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_250"
                     title="Cancer Research &quot;Giant&quot; Lawrence Garfinkel Dies at 88"
                     score="-0.001"
                     href="http://www.medpagetoday.com/Pulmonology/Smoking/tb/18108?impressionId=1265777032194"
                     
      &lt;p&gt;Epidemiologist Lawrence Garfinkel, MA, a legendary researcher for the American Cancer Society whose work helped establish a link between cancer and smoking and other activities, died of cardiovascular disease Thursday in Seattle, Washington at 88.&lt;/p&gt;
&lt;p&gt;&quot;The American Cancer Society today mourns the loss of one of its most important historical figures,&quot; said John R. Seffrin, PhD, the society&apos;s chief executive officer.&lt;/p&gt;
&lt;p&gt;&quot;Larry Garfinkel joined the American Cancer Society as a young scientist in 1947, and for more than four decades played an instrumental role in expanding knowledge of and reducing death from smoking.&quot;&lt;/p&gt;
&lt;p&gt;Garfinkel&apos;s 1982 Cancer Prevention Study-II (CPS-II) is the largest contemporary study of tobacco and mortality, with 1.2 million participants and 77,000 data-compiling volunteers across 50 states, the District of Columbia, and Puerto Rico.&lt;/p&gt;
&lt;p&gt;CPS-II uncovered the effects of lifestyle factors, such as obesity, alcohol consumption, medications, genetic elements, that affect cancer and other chronic diseases, the analysis of which still reveals important clues about cancer today.&lt;/p&gt;
&lt;p&gt;The study also found lung cancer mortality rates in women increased five-fold from data collected in the original Cancer Prevention Study, while cancer rates among non-smoking women remained the same. This information provided strong evidence that lung cancer was almost exclusively a disease found in smokers.&lt;/p&gt;
&lt;p&gt;Garfinkel was born on January 11, 1922 in Manhattan&apos;s Lower East Side and was raised in the South Bronx.&lt;/p&gt;
&lt;p&gt;He served in the army during World War II, where he was seriously injured in northern France in August, 1944.&lt;/p&gt;
&lt;p&gt;Ultimately, Garfinkel graduated from the City College of New York and received a Masters Degree from Columbia University. He also received several honorary doctorates.&lt;/p&gt;
&lt;p&gt;Garfinkel began work for the ACS in 1947.&lt;/p&gt;
&lt;p&gt;He assisted E. Cuyler Hammond, MD, and Daniel Horn, MD, in the first ACS prospective mortality study of 187,783 males in the late 1940&apos;s by coordinating much of the field work, including training thousands of ACS volunteers in data collection techniques.&lt;/p&gt;
&lt;p&gt;Garfinkel acted as the co-principal investigator of the larger Cancer Prevention Study I (CPS-I) in 1959. The study enrolled 1 million participants across 25 states and required over 68,000 volunteers to collect data.&lt;/p&gt;
&lt;p&gt;In the 1960s, he contributed to more than two dozen major papers on the relation between smoking and health. He was co-author of one of the first reports combining epidemiology with pathology and provided some of the first direct evidence of lung damage related to smoking.&lt;/p&gt;
&lt;p&gt;Garfinkel also contributed to issuance of the landmark 1964 Surgeon General&apos;s report on smoking and health.&lt;/p&gt;
&lt;p&gt;He was appointed director of ACS research in 1979 after Hammond&apos;s retirement.&lt;/p&gt;
&lt;p&gt;Garfinkel retired from the ACS in 1989. Over the course of his career, he had contributed to more than 100 journal articles.&lt;/p&gt;
&lt;p&gt;Richard D. Klausner, MD, then-director of the National Cancer Institute, said at the time: &quot;Few individuals have contributed as much to our present-day knowledge about the disease consequences of smoking.&lt;/p&gt;
&lt;p&gt;&quot;His remarkable achievement is an important reminder what a tremendous impact an individual can make, and inspires all of us to continue the fight against cancer.&quot;&lt;/p&gt;
&lt;p&gt;Garfinkel continued to volunteer with the ACS after his retirement and taught biostatistics at the New York University Dental School.&lt;/p&gt;
&lt;p&gt;He is survived by his brothers, Harold and Melvin; his sons, Martin and Herb; a daughter-in-law, Margaret Cary, and two grandchildren.&lt;/p&gt;

    </recommendedItem>
</recommendedContent>