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    <recommendedItem id="20100101_19_357"
                     title="Targeted Therapy Disappoints in Recurrent Brain Tumors (CME/CE)"
                     score="0.008"
                     href="http://www.medpagetoday.com/HematologyOncology/BrainCancer/tb/18237?impressionId=1265810708411"
                     
      &lt;p&gt;High hopes for treating recurrent glioblastoma with the novel, targeted antiangiogenic enzastaurin have been diminished by disappointing phase III results.&lt;/p&gt;
&lt;p&gt;The study failed its primary endpoint with a median progression-free survival of 1.5 months compared with 1.6 months on conventional lomustine (CeeNu, &lt;em&gt;P&lt;/em&gt;=0.08).&lt;/p&gt;
&lt;p&gt;Nor were there any other significant benefits, despite generally good tolerability, Wolfgang Wick, MD, of the University of Heidelberg, Germany, and colleagues reported online in the &lt;em&gt;Journal of Clinical Oncology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;In an earlier &lt;a href=&quot;http://www.medpagetoday.com/HematologyOncology/BrainCancer/1062&quot; mce_href=&quot;http://www.medpagetoday.com/HematologyOncology/BrainCancer/1062&quot; target=&quot;_blank&quot;&gt;phase II study&lt;/a&gt;, the drug shrank tumors in 22% of heavily pretreated patients with recurrent glioblastoma, a heavily vascular cancer and one of the toughest to treat.&lt;/p&gt;
&lt;p&gt;The experimental agent is a potent and selective inhibitor of protein kinase C-beta, which mediates the most important regulator of vessel growth in glioma.&lt;/p&gt;
&lt;p&gt;Even so, jumping directly into a phase III study before the final results of a phase II study might have been premature, even with a strong preclinical rationale, the authors and an accompanying editorial said.&lt;/p&gt;
&lt;p&gt;Evanthia Galanis, MD, DSc, and Jan C. Buckner, MD, both of the Mayo Clinic in Rochester, Minn., wrote in an editorial that response rate &quot;can be particularly misleading as an indicator of antitumor activity of antiangiogenic agents.&quot;&lt;/p&gt;
&lt;p&gt;Reduced vascular permeability can appear as improvement on enhanced MRI, without true antitumor effect, the editorialists noted. Nor does response rate correlate well with progression-free or overall survival in this type of cancer, they wrote.&lt;/p&gt;
&lt;p&gt;Still, they cautioned, these negative phase III results aren&apos;t the final word on the drug whose modest activity was comparable to standard treatment  --  and with satisfactory tolerability.&lt;/p&gt;
&lt;p&gt;&quot;It would therefore still be worth incorporating enzastaurin in rationally designed combinatorial regimens, especially if based on a strong mechanistic rationale or preclinical demonstration of synergistic activity,&quot; Galanis and Buckner wrote.&lt;/p&gt;
&lt;p&gt;The study randomized patients with World Health Organization grade 4 glioblastoma to receive six-week cycles of open-label enzastaurin 500 mg/d (1,125-mg loading dose on day one) or lomustine (100 to 130 mg/m&lt;sup&gt;2&lt;/sup&gt; on day one).&lt;/p&gt;
&lt;p&gt;It was stopped at the planned interim futility analysis after enrollment of 266 patients.&lt;/p&gt;
&lt;p&gt;The researchers had powered the study for a 45% improvement in median progression-free survival, but found it actually tended to be 28% better with lomustine (HR 1.28, 95% CI 0.97 to 1.70).&lt;/p&gt;
&lt;p&gt;Six-month progression-free survival rates were 11.1% with the experimental treatment, compared with 19.0% among controls (&lt;em&gt;P&lt;/em&gt;=0.13).&lt;/p&gt;
&lt;p&gt;Overall survival, too, was similar at 6.6 and 7.1 months, respectively (HR 1.20, &lt;em&gt;P&lt;/em&gt;=0.25). Objective response rate showed no differences either (&lt;em&gt;P&lt;/em&gt;=0.501).&lt;/p&gt;
&lt;p&gt;Patient-reported time to deterioration  --  measured on the Functional Assessment of Cancer Therapy&amp;#8211;Brain questionnaire  --  was 2.27 months with enzastaurin compared with 2.33 months for lomustine (&lt;em&gt;P&lt;/em&gt;=0.54).&lt;/p&gt;
&lt;p&gt;Results likewise were similar between the groups for physical and functional well-being and for brain tumor&amp;#8211;specific concerns (&lt;em&gt;P&lt;/em&gt;&amp;gt;0.05).&lt;/p&gt;
&lt;p&gt;Adverse event rates were not different between groups, although more were drug-related in the lomustine group (62% versus 44%, &lt;em&gt;P&lt;/em&gt;=0.008).&lt;/p&gt;
&lt;p&gt;Enzastaurin did have the advantage of less hematologic toxicity overall (&lt;em&gt;P&lt;/em&gt;&amp;#8804;0.001), and specifically for grade 3 to 4 adverse events (one versus 46 events, &lt;em&gt;P&lt;/em&gt;&amp;#8804;0.001).&lt;/p&gt;
&lt;p&gt;Study deaths in the enzastaurin group totaled 11, including four due to adverse events and one drug-related; while the four deaths in lomustine-treated patients were disease-related.&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 Eli Lilly, including writing and editorial support.&lt;/p&gt;&lt;p&gt;Wick and co-authors reported financial conflicts of interest with Eli Lilly, including employment and stock ownership for some.&lt;/p&gt;&lt;p&gt;Co-authors also reported financial conflicts of interest with Merck, Genentech, Enzon, Schering-Plough, and AstraZeneca.&lt;/p&gt;&lt;p&gt;Galanis reported conflicts of interest with Merck, Bristol-Myers Squibb, Gradalis, Genetech, and Bayer Pharmaceuticals.&lt;/p&gt;&lt;p&gt;Buckner reported conflicts of interest with Merck Serono, Genentech, Excelixis, Bayer Pharmaceuticals, Bristol-Myers Squibb, and Anti-Sense Pharma.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_1245"
                     title="AACR: MRI Can Pick Out Mutation in Glioblastoma"
                     score="-0.006"
                     href="http://www.medpagetoday.com/MeetingCoverage/AACR/tb/13880?impressionId=1265810708411"
                     
       DENVER, April 23 -- Magnetic resonance imaging has been used -- for what investigators think is the first time -- to pick out a genetic mutation in a brain tumor. 
              &lt;p&gt; 
              &lt;p&gt;In glioblastoma multiforme, changes in regional cerebral blood volume picked up by MR perfusion-weighted imaging can indicate that the tumor carries a particularly aggressive oncogene, according to Donald O&apos;Rourke, M.D., of the University of Pennsylvania.
              &lt;p&gt; 
              &lt;p&gt;&quot;To my knowledge this is the first demonstration that an MRI technique -- or any imaging technique -- can predict with very high specificity and positive predictive value the mutational status of a human tumor,&quot; Dr. O&apos;Rourke said at the American Association for Cancer Research meeting.
              &lt;p&gt; 
              &lt;p&gt;The &quot;major impetus&quot; for the research, Dr. O&apos;Rourke said, was the recent &quot;explosion&quot; in both genomics and imaging methods.
              &lt;p&gt; 
              &lt;p&gt;MRI is now used to classify tumors, select treatment, and to evaluate responses, he said, and he and his colleagues wished to extend those uses to glioblastoma.
              &lt;p&gt; 
              &lt;p&gt;In particular, they thought that variant III of the epidermal growth factor receptor (EGFR) might be associated with changes in regional cerebral blood volume that could be distinguished from those caused by other forms of the oncogene.
              &lt;p&gt; 
              &lt;p&gt;The so-called EGFRvIII mutation occurs in about 35% of glioblastomas and is associated with poorer survival. It up-regulates vascular endothelial growth factor (VEGF), a pro-angiogenic factor.
              &lt;p&gt; 
              &lt;p&gt;The researchers tested tissue samples from 35 patients with glioblastoma. Then they tracked blood volume changes in routine MRIs taken to follow the tumors, Dr. O&apos;Rourke said.
              &lt;p&gt; 
              &lt;p&gt;In each of eight different independent methods used to evaluate the images, he said, &quot;there was a significant correlation between cerebral blood volume and EGFRvIII.&quot;
              &lt;p&gt; 
              &lt;p&gt;Interestingly, the increase in blood volume was not completely explained by the effects of EGFRvIII on VEGF, he said, possibly because the oncogene affects other pro-angiogenic factors.
              &lt;p&gt; 
              &lt;p&gt;Nonetheless, the model developed by the researchers using blood volume to predict EGFRvIII status was highly predictive and even better when blood volume and VEGF were combined, Dr. O&apos;Rourke said.
              &lt;p&gt; 
              &lt;p&gt;Specifically, every unit increase in regional cerebral blood volume more than doubled the odds that the tumor had EGFRvIII. The odds ratio was 2.49, with a 95% confidence interval from 1.12 to 5.56, which was significant at &lt;em&gt;P&lt;/em&gt;=0.026.
              &lt;p&gt; 
              &lt;p&gt;In the model with blood volume and VEGF combined, the odds ratio was 2.7, with a 95% confidence interval from 1.04 to 6.99, which was significant at &lt;em&gt;P&lt;/em&gt;=0.041.
              &lt;p&gt; 
              &lt;p&gt;&quot;What was impressive to us was the degree of the prediction model that we were able to develop from our data,&quot; Dr. O&apos;Rourke said.
              &lt;p&gt; 
              &lt;p&gt;The theme of the meeting this year is &quot;science, synergy, and success,&quot; said 
              &lt;p&gt;Michael Caligiuri, M.D., of Ohio State University and program chair of the conference, and the report by Dr. O&apos;Rourke showed the value of &quot;team science&quot; in achieving those goals.
              &lt;p&gt; 
              &lt;p&gt;&quot;Science today is no longer done in an individual laboratory -- it&apos;s across a spectrum of collaborators in the lab, transitioning into the clinic and then back into the lab,&quot; he said.
              &lt;p&gt; 
              &lt;p&gt;&lt;table cellspacing=&quot;0&quot; hspace=&quot;1&quot; style=&quot;border-style:solid; border-width:1px; border-color:#8dabbc; font-family:arial; font-size:12px; background-color:#DBE9F2; padding:5px 5px 5px 5px;&quot;&gt;
&lt;tr&gt;&lt;td&gt; Dr. O&apos;Rourke did not report study support or conflicts.&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;
    </recommendedItem>
    <recommendedItem id="20090101_1_634"
                     title="ASTRO: Hair Loss May Be Stopped by Intensity-Modulated Palliative Brain Radiation"
                     score="-0.007"
                     href="