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    <recommendedItem id="20100101_19_357"
                     title="Targeted Therapy Disappoints in Recurrent Brain Tumors (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/HematologyOncology/BrainCancer/tb/18237?impressionId=1265765952316"
                     
      &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="20100101_19_100"
                     title="PET-CT Finds More Cancers than Standard Neurologic Screens (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/Neurology/GeneralNeurology/tb/17905?impressionId=1265765952316"
                     
      In patients who have neurologic symptoms indicative of cancer, whole-body positron emission tomography-computed tomography (PET-CT) may improve the detection rates when other screening test results are negative, researchers say.&lt;br&gt;
&lt;br&gt;The use of PET-CT increased the diagnostic yield for cancer by 18% in patients with suspected paraneoplastic neurologic disorders for whom results of standard oncologic tests were negative, Andrew McKeon, MB, MRCPI, of the Mayo Clinic in Rochester, Minn., and colleagues reported online in &lt;em&gt;Archives of Neurology&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;&quot;This is important in that firstly, cancer is detected,&quot; McKeon said in an interview with &lt;em&gt;MedPage Today&lt;/em&gt;. &quot;The cancers were treated in all patients and seven of 10 patients went into remission. In addition, five of 10 had improvements in neurologic problems through cancer treatment or treatment with immunotherapies.&quot;&lt;br&gt;
&lt;br&gt;Paraneoplastic neurologic disorders occur in some people with cancer  --  including lung, breast, or ovarian cancer  --  and develop when cancer-fighting antibodies mistakenly attack cells in the nervous system.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;Routine screening for cancer in patients with such symptoms  --  including physical examination, CT of the chest, abdomen and pelvis, and mammography or testicular ultrasound  --  may be unrevealing. That&apos;s often because cancers detected in a paraneoplastic context are frequently small and restricted to one site.&lt;/p&gt;
&lt;p&gt;Detecting autoantibodies via serologic testing refines the search and detects cancer in about 70% of seropositive patients, the researchers wrote.&lt;/p&gt;
&lt;p&gt;&quot;Once [a paraneoplastic antibody] is detected and the suspicion is raised for underlying cancer, the challenge is to try and find it,&quot; McKeon said. &quot;So we wanted to try and see what sort of patients we would find cancers in with PET-CT and try and predict what type of patients the cancers would be found in.&quot;&lt;/p&gt;
&lt;p&gt;PET-CT allows the detection of radiolabeled fludeoxyglucose preferentially taken up by highly metabolically active cancers.&lt;/p&gt;
&lt;p&gt;To evaluate its ability to detect cancer, the researchers conducted a literature review for studies that evaluated the utility of PET for cancer diagnosis in patients with paraneoplastic neurologic disorders. Then they did a retrospective review of medical records of 56 patients with clinically suspected paraneoplastic neurologic disorders who&apos;d had PET-CT scans after standard evaluations that turned out to be negative.&lt;/p&gt;
&lt;p&gt;Median age of the patients at symptom onset was 61.&lt;/p&gt;
&lt;p&gt;Before their PET-CT, patients had had a median of three other screening tests; the most common was CT of the chest, abdomen, and pelvis.&lt;/p&gt;
&lt;p&gt;Using PET-CT, the researchers detected abnormalities suggestive of cancer in 22 patients, or 39% of the total population.&lt;/p&gt;
&lt;p&gt;Among these, cancer was confirmed histologically in 10 patients as follows: &lt;ul&gt; &lt;li&gt;Thyroid papillary cell carcinomas: 2&lt;/li&gt; &lt;li&gt;Solitary lymph nodes: 2 adenocarcinomas, 1 small cell carcinoma&lt;/li&gt; &lt;li&gt;Tonsil squamous cell carcinoma: 1&lt;/li&gt; &lt;li&gt;Lung carcinomas: 1 adenocarcinoma, 1 small cell, 1 squamous cell&lt;/li&gt; &lt;li&gt;Colon adenocarcinoma: 1&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;All 10 patients were seropositive for paraneoplastic autoantibodies.&lt;/p&gt;
&lt;p&gt;Four of the 10 cancers detected using PET-CT were outside the anatomical scope of CT of the chest, abdomen, and pelvis. The six other cancers were too small to be detected by an appropriate regional CT, the researchers wrote.&lt;/p&gt;
&lt;p&gt;Among the other 12 patients who had abnormalities on PET-CT, two had premalignant lesions, one had a noncaseating granuloma, five had negative biopsy results, and other PET-directed evaluations without biopsy were negative in two. There were no further evaluations in the remaining patients.&lt;/p&gt;
&lt;p&gt;The researchers found that detection of a well-characterized neuronal nuclear or cytoplasmic paraneoplastic autoantibody was associated with a successful PET-CT-directed cancer search (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Since the majority of cancers were detected in a limited-stage, 70% of treated patients went into remission. Five patients had sustained improvements in neurologic symptoms after a median follow-up of 11 months.&lt;/p&gt;
&lt;p&gt;Based on their literature review, the present study had a higher detection rate of cancer for PET-CT (12% versus 18%), which may be explained by a larger number of patients available for follow-up in the present study or the enhanced sensitivity of PET-CT over PET alone.&lt;/p&gt;
&lt;p&gt;Still, a caveat is the screen&apos;s high false-positive rate.&lt;/p&gt;
&lt;p&gt;&quot;PET-CT is very sensitive, since it can pick up hypermetabolic tissue,&quot; McKeon said. &quot;But tissue can be hypermetabolic for different reasons.&quot;&lt;/p&gt;
&lt;p&gt;He added that PET-CT &quot;is by no means the be-all and end-all of this. It&apos;s just a helpful screening tool in patients where a cancer is suspected.&quot;&lt;/p&gt;
&lt;p&gt;They acknowledged that their study was limited by its retrospective design and small sample size, but the researchers concluded that &quot;recognizing the limitations of PET-CT, we favor this modality for initial oncologic evaluation of patients in whom a paraneoplastic neurologic disorder is strongly suspected.&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;A co-author stands to receive royalties for commercial assays to detect aquaporin-4-specific autoantibodies.&lt;/p&gt;&lt;p&gt;The other researchers reported no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_1_156"
                     title="Glioma and Cell Phones -- Again No Link"
                     score="-0.005"
                     href="