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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=1265795499411"
                     
      &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_346"
                     title="Daytime Sleepiness More Common in Young (CME/CE)"
                     score="0.01"
                     href="http://www.medpagetoday.com/PrimaryCare/SleepDisorders/tb/18221?impressionId=1265795499411"
                     
      &lt;p&gt;Compared with 20-somethings and seniors, middle-age adults are less likely to suffer daytime sleepiness when they don&apos;t get a good night&apos;s sleep, according to a small study.&lt;/p&gt;
&lt;p&gt;When three groups of healthy adults  --  young (20 to 30 years old), middle-age (40 to 55) and older (66 to 83)  --  were studied over four nights, slow wave sleep decreased and the number of nocturnal awakenings progressively increased with age, wrote Derk-Jan Dijk, PhD, of the Surrey Sleep Center at the University of Surrey in Guildford, England, and colleagues in the Feb. 1 issue of &lt;em&gt;Sleep.&lt;/em&gt;&lt;/p&gt;

&lt;p&gt;As the likelihood for eight hours of uninterrupted deep sleep decreased with age, there was no increase in the likelihood of daytime sleepiness, which led Dijk and colleagues to conclude that as people age there may be a change in the &quot;sleep (duration and depth) required to maintain alertness.&quot;&lt;/p&gt;
&lt;p&gt;Based on that observation, the authors wrote that it could be argued that &quot;an eight-hour episode rich in [slow wave sleep] is insufficient for young adults but that an eight-hour sleep episode with less [slow wave sleep] is sufficient for older adults.&quot;&lt;/p&gt;
&lt;p&gt;As a result, middle-age and older adults are less likely to build up &quot;sleep debt&quot; during the daylight hours, so they manage with less time in deep sleep at night, less homeostatic sleep pressure.&lt;/p&gt;
&lt;p&gt;The authors hypothesized that this apparent need for less sleep may be a factor in age-related insomnia.&lt;/p&gt;
&lt;p&gt;If older adults are unaware of the need for less sleep, &quot;their self-selected time in bed, which provides an input to the sleep homeostat, may become maladaptive and lead to reduced sleep consolidation and associated complaints.&quot;&lt;/p&gt;
&lt;p&gt;Dijk and colleagues recruited 44 young adults, 35 middle-age adults, and 31 older adults for their study. All were healthy at baseline and all were initially assessed for an eight-hour nocturnal sleep episode.&lt;/p&gt;
&lt;p&gt;They were then randomized to two nights of either selective short wave sleep interruption by acoustic stimuli or sleep without disruption, followed by one night of recovery sleep.&lt;/p&gt;
&lt;p&gt;Two standardized measurement tools, the Multiple Sleep Latency Test (MSLT) and the Karolinska Sleepiness Scale (KSS), were used to assess objective and subjective sleep propensity.&lt;/p&gt;
&lt;p&gt;&quot;Total sleep time per eight hour time in bed decreased significantly and progressively across the age groups such that older adults slept approximately 20 minutes less than middle-aged, who slept 23 minutes less than young adults,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;The reduction in total sleep time &quot;was primarily related to an increase in the number of awakenings and the duration of wakefulness after sleep onset, rather than an increase in latency to sleep onset.&quot;&lt;/p&gt;
&lt;p&gt;As a result, sleep efficiency decreased significantly from 92.1% for the youngest group, to 82% for the older group (effect of age, &lt;em&gt;P&amp;lt;&lt;/em&gt;0.0001).&lt;/p&gt;
&lt;p&gt;The subjective sleep propensity tests revealed that &quot;young people were significantly sleepier than the middle-age people, who were the least sleepy of the three groups.&quot; Daytime sleepiness for the oldest group &quot;fell in between the other two groups [and] was not significantly different from either.&quot;&lt;/p&gt;
&lt;p&gt;All three groups, regardless of age, demonstrated increased daytime sleepiness following a night of experimental disruption of slow wave sleep, but when the participants had an uninterrupted eight hours of deep sleep, it was only the youngest group that was drowsy during the daytime hours.&lt;/p&gt;
&lt;p&gt;The authors noted that although there was less daytime sleepiness among middle-age and older adults in this study, sleep propensity was not measured during the evening hours, so it was possible that the age-related difference might diminish at twilight.&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 sponsored by H. Lundbeck A/S.&lt;/p&gt;&lt;p&gt;Dijk reported receiving research support from the Air Force Office of Scientific Research, the Biotechnology and Biological Sciences Research Council, GlaxoSmithKline, H. Lundbeck A/S, Merck, Pfizer, Philips Lighting, sanofi-aventis, and Takeda.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_1_634"
                     title="ASTRO: Hair Loss May Be Stopped by Intensity-Modulated Palliative Brain Radiation"
                     score="-0.005"
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