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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=1265805193408"
                     
      &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_406"
                     title="AAPM: Opioid Gains Long-Term Control of Neuropathic Cancer Pain (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/MeetingCoverage/AAPM/tb/18316?impressionId=1265805193408"
                     
      &lt;p&gt;SAN ANTONIO  --  Patients with neuropathic cancer pain obtained consistent, long-term pain control with extended-release oxymorphone (Opana), according to results of a one-year, open-label extension study.&lt;/p&gt;
&lt;p&gt;Patients reported pain in the mild range throughout most of the follow-up, and only 11% discontinued because of lack of efficacy, Errol Gould, PhD, of Endo Pharmaceuticals in Chadds Ford, Pa., reported here at the American Academy of Pain Medicine meeting. The company manufactures Opana.&lt;/p&gt;
&lt;p&gt;No unexpected adverse events occurred.&lt;/p&gt;
&lt;p&gt;&quot;Current clinical guidelines recommend opioids as second- or third-line treatment for chronic neuropathic pain,&quot; Gould said in an interview. &quot;These results suggest that oxymorphone extended release may be a viable long-term option for patients with neuropathic pain.&quot;&lt;/p&gt;
&lt;p&gt;The findings came from a one-year extension of a multicenter, open-label, noncontrolled short-term study of patients with cancer-related chronic pain.&lt;/p&gt;
&lt;p&gt;Of 44 patients who entered the extension phase, 27 had pain that was primarily neuropathic in origin. The diagnosis of neuropathic pain was based on clinician judgment, with no prespecified diagnostic criteria for guidance.&lt;/p&gt;
&lt;p&gt;Patients began treatment in the extension phase with their ending dose from the short-term study. Dose adjustments to improve pain control or tolerability were allowed throughout the 52-week extension phase.&lt;/p&gt;
&lt;p&gt;Ten of the 27 patients completed the extension study. Principal reasons for withdrawal were adverse events, patient request, loss of effectiveness, and nonadherence.&lt;/p&gt;
&lt;p&gt;The median duration from initiation of long-term maintenance to final visit was 22 weeks. Baseline pain intensity averaged 32.9 on a 100-point scale and 32.6 at final visit. Mean least pain intensity was 13.8 at baseline and 16.2 at final visit, and worst pain intensity averaged 76.3 at baseline and 66.5 at final visit.&lt;/p&gt;
&lt;p&gt;&quot;Regression analysis showed that pain intensity changed very little throughout follow-up,&quot; Gould said.&lt;/p&gt;
&lt;p&gt;The median oxymorphone dose increased from 80 mg at baseline to 160 mg at 52 weeks.&lt;/p&gt;
&lt;p&gt;Eleven (41%) patients reported at least one treatment-related adverse event. The most common events were dry mouth, constipation, and fatigue. The only serious adverse event was an episode of depressed consciousness.&lt;/p&gt;
&lt;p&gt;&quot;Patients required some gradual increases in dosage over time, but that&apos;s consistent with the nature of the disease,&quot; said Gould.&lt;/p&gt;
&lt;p&gt;Not long ago opioids were considered ineffective for neuropathic pain, he added. This study provided additional evidence in support of opioids&apos; effectiveness in controlling neuropathic pain.&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 Endo Pharmaceuticals, which manufactures Opana.&lt;/p&gt;&lt;p&gt;Gould and another co-author are employees of Endo Pharmaceuticals.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_342"
                     title="Stem Cell Transplant Source Does Not Affect Long-Term Leukemia Outcomes (CME/CE)"
                     score="0.008"
                     href="http://www.medpagetoday.com/HematologyOncology/Leukemia/tb/18220?impressionId=1265805193408"
                     
      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="0.003"
                     href="http://www.medpagetoday.com/ProductAlert/DevicesandVaccines/tb/18158?impressionId=1265805193408"
                     
      &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_19_3986"
                     title="Cancer Report Card Reveals Decline in Disease and Death"
                     score="-0.005"
                     href="http://www.medpagetoday.com/HematologyOncology/Hematology/tb/17385?impressionId=1265805193408"
                     
      &lt;p&gt;Cancer incidence and mortality continue to decline, with the most dramatic decreases in lung, prostate, and colorectal cancers among men, and breast and colorectal cancers in women, according to the latest national report card.&lt;/p&gt;
&lt;p&gt;&quot;Overall cancer incidence rates for all racial/ethnic groups combined decreased by 0.7% per year during 1999-2006 for both sexes combined, by 1.3% per year during 2000-2006 for men, and by 0.5% per year during 1998-2006 for women,&quot; authors from the American Cancer Society, the CDC, the National Cancer Institute, and the North American Association of Central Cancer Registries concluded.&lt;/p&gt;
&lt;p&gt;The report, which has become an annual ritual, was published online in the ACS journal, &lt;em&gt;Cancer.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;There has been a decline in cancer death rates since the early 1990s and that trend appears to be durable.&lt;/p&gt;
&lt;p&gt;&quot;The decreases were slightly larger for men, who had declines of 1.5% per year during 1993-2001 and 2.0% per year during 2001-2006 compared with women, whose cancer death rates declined 0.8% per year during 1994-2002 and 1.5% per year during 2002-2006,&quot; the authors wrote.&lt;/p&gt;
&lt;p&gt;But the news was not all good. As men saw decreased rates of prostate, lung, oral, stomach, brain, and colorectal cancers, there was a concurrent increase in the cancers of the kidney, renal, liver, and esophagus  --  as well as increases in leukemia, myeloma, and melanoma of the skin.&lt;/p&gt;
&lt;p&gt;For women the story was similar -- decreased rates of breast, colorectal, ovarian, cervical, uterine corpus, and oral cancers, but an uptick in lung, thyroid, pancreas, bladder, and kidney cancers, as well as increases in non-Hodgkin lymphoma, melanoma, and leukemia.&lt;/p&gt;
&lt;p&gt;Colorectal cancer is a focus of this year&apos;s report, not a surprising choice because the news here is good: &quot;CRC death rates have declined since 1984 in both men and women, with an accelerated rate of decline since 2002 (for men) and 2001 (for women).&quot;&lt;/p&gt;
&lt;p&gt;And a &quot;microsimulation model&quot; suggests that death rates from colorectal cancer could be reduced by 36% over the next decade if &quot;1995-2000 trends for risk factor prevalence, screening, and treatment continue.&quot;&lt;/p&gt;
&lt;p&gt;But the authors point out that increased obesity among younger Americans could derail this trend.&lt;/p&gt;
&lt;p&gt;The annual report often paints a rosy picture based on a patchwork of data collected from a number of sources and analyzed using a complex array of statistical methods.&lt;/p&gt;
&lt;p&gt;The report&apos;s lead author, Brenda K. Edwards, PhD, of the National Cancer Institute, and her colleagues, provide detailed descriptions of potential problems  --  so much so that the report includes two pages of possible limitations.&lt;/p&gt;

    </recommendedItem>
</recommendedContent>