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<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_307"
                     title="Good Results in Poor-Risk Rectal Cancer (CME/CE)"
                     score="0.006"
                     href="http://www.medpagetoday.com/HematologyOncology/ColonCancer/tb/18169?impressionId=1265793737162"
                     
      &lt;p&gt;Patients with high-risk rectal cancer had high response and three-year survival rates on a regimen of preoperative chemotherapy, followed by standard chemoradiation and then surgical resection, according to results of a multicenter study.&lt;/p&gt;
&lt;p&gt;Three-fourths of patients had objective responses to neoadjuvant chemotherapy, increasing to 89% after chemoradiation, researchers reported online in &lt;em&gt;The Lancet Oncology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Additionally, 97% of patients who underwent surgery had microscopically clear surgical margins. At three years, 83% of patients remained alive, including almost 70% who were progression free.&lt;/p&gt;
&lt;p&gt;&quot;Intensification of systemic therapy with neoadjuvant combination chemotherapy before standard treatment is feasible in poor-risk, potentially operable rectal cancer, with acceptable safety and promising long-term outcomes,&quot; David Cunningham, MD, of the Royal Marsden Hospital in Sutton, England, and co-authors concluded.&lt;/p&gt;
&lt;p&gt;&quot;Future development of this multidisciplinary treatment strategy in randomized trials is warranted.&quot;&lt;/p&gt;
&lt;p&gt;Although surgery remains the primary and potentially curative therapy for localized rectal cancer, local recurrence rates as high as 40% have been reported with conventional resection.&lt;/p&gt;
&lt;p&gt;The introduction of standardized surgery and total mesorectal excision reduced local recurrence rates to less than 10%, which has been associated with improved survival, the authors noted.&lt;/p&gt;
&lt;p&gt;Preoperative radiotherapy and then chemoradiation further reduced the risk of local recurrence, but did not improve overall survival compared with surgery alone.&lt;/p&gt;
&lt;p&gt;Combination chemotherapy has led to higher response rates and progression-free survival compared with monotherapy for patients with advanced rectal cancer, the authors continued. Adjuvant chemotherapy containing oxaliplatin (Eloxatin) also has improved outcomes in resected colon cancer.&lt;/p&gt;
&lt;p&gt;Given that oxaliplatin-fluoropyrimidine combinations have become a preferred standard, investigators designed a clinical trial of high-risk rectal cancer to investigate preoperative treatment with oxaliplatin and capecitabine (Xeloda).&lt;/p&gt;
&lt;p&gt;A previous report involving the first 77 patients enrolled in the trial showed substantial tumor regression, rapid improvement in symptoms, and a high rate of clear surgical margins (&lt;em&gt;J Clin Oncol&lt;/em&gt; 2006; 24: 668-74).&lt;/p&gt;
&lt;p&gt;Nine treatment-related cardiac events occurred in eight of the 77 patients, prompting a protocol amendment to exclude patients with a recent history of clinically significant cardiac problems.&lt;/p&gt;
&lt;p&gt;The updated results comprised 105 patients, and only one cardiac event occurred after the change in eligibility criteria, the authors wrote.&lt;/p&gt;
&lt;p&gt;All of the patients had MRI-defined, poor-risk but nonmetastatic rectal cancer. Patients received four cycles of neoadjuvant chemotherapy over 12 weeks, followed by chemoradiotherapy consisting of a total radiation dose of 54 Gy administered over six weeks, plus daily capecitabine.&lt;/p&gt;
&lt;p&gt;After total mesorectal excision, patients received 12 weeks of adjuvant capecitabine.&lt;/p&gt;
&lt;p&gt;The primary endpoint was pathologic complete response, and median follow-up was 55 months.&lt;/p&gt;
&lt;p&gt;Radiologically confirmed response rates were 74% after neoadjuvant chemotherapy and 89% after chemoradiation. Of 97 patients who had surgery, 93 had microscopically clear margins, and 21 of 105 patients had pathologic complete responses.&lt;/p&gt;
&lt;p&gt;Three-year progression-free and overall survival were 68% and 83%, respectively. Among patients who had surgery, three-year, relapse-free survival was 74%.&lt;/p&gt;
&lt;p&gt;&quot;Our findings show the feasibility of neoadjuvant chemotherapy with capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision, which accord with the initial results of this study,&quot; the authors declared.&lt;/p&gt;
&lt;p&gt;&quot;High radiological response rates to preoperative treatment were recorded, and the number of pathological complete responses surpassed the prespecified number needed to meet the primary objective of this trial.&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;The study was supported by England&apos;s National Health Service and sanofi-aventis.&lt;/p&gt;&lt;p&gt;Cunningham and co-author Niall Tebbutt disclosed relationships with Roche and sanofi-aventis.&lt;/p&gt;&lt;p&gt;Co-author Ian Chau disclosed relationships with Roche and sanofi-aventis.&lt;/p&gt;&lt;p&gt;Co-author Yu Jo Chua disclosed relationships with Roche and sanofi-aventis.&lt;/p&gt;&lt;p&gt;Co-author Gina Brown disclosed a relationship with sanofi-aventis.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_259"
                     title="ASCO GI: Gene Therapy Shows Promise in Esophageal Cancer (CME/CE)"
                     score="0.001"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCOGI/tb/18122?impressionId=1265793737162"
                     
      &lt;p&gt;ORLANDO  --  Injecting the gene encoding for tumor necrosis factor-alpha (TNF-alpha) directly into tumors led to pathologic complete responses in a third of patients and a median survival of four years in a small study of patients with locally advanced esophageal cancer.&lt;/p&gt;
&lt;p&gt;The gene-therapy strategy led to nodal conversion and downstaging in a majority of patients, most of whom underwent surgical resection following chemoradiation and the intratumoral injections of TNF.&lt;/p&gt;
&lt;p&gt;Patients who received the three lowest doses of TNF in the dose-finding study had a five-year median survival of 56%.&lt;/p&gt;
&lt;p&gt;&quot;This represents an encouraging increase in survival relative to historical controls,&quot; Kenneth J. Chang, MD, of the University of California Irvine, reported here at the Gastrointestinal Cancers Symposium. &quot;These results warrant further evaluation.&quot;&lt;/p&gt;
&lt;p&gt;However, another investigator in the multicenter study cautioned that the trial was stopped because of treatment-related deaths that have not been fully explained, and that the regimen is complicated and time-consuming.&lt;/p&gt;
&lt;p&gt;The primary objective of the study was to assess the safety, feasibility, and tolerability of weekly intratumoral injections of TNFerade, a second-generation replication-deficient adenovector, carrying the transgene encoding human TNF-alpha, regulated by the radiation-inducible promotor Egr-1.&lt;/p&gt;
&lt;p&gt;Upon its release inside a tumor, the gene therapy stimulates TNF production to help destroy the tumor. The therapy was developed for use with radiation and conventional chemotherapy.&lt;/p&gt;
&lt;p&gt;The gene therapy has received FDA fast-track status for evaluation as treatment for pancreatic cancer.&lt;/p&gt;
&lt;p&gt;Chang reported results from a dose-finding study involving 24 patients with locally advanced esophageal cancer. All were surgical candidates before enrollment. Each patient received five weekly injections of TNF concurrent with 5-FU, cisplatin, and external-beam radiation therapy. The TNF doses evaluated ranged from 4 x 10&lt;sup&gt;8&lt;/sup&gt; to 4 x 10&lt;sup&gt;11&lt;/sup&gt; PU.&lt;/p&gt;
&lt;p&gt;Staging results showed that all but one of the patients had T3 disease, and 18 had nodal involvement (N1).&lt;/p&gt;
&lt;p&gt;The preoperative therapy was administered over 5.5 weeks. Following a recovery period of five to 11 weeks, patients were to undergo surgical resection, which ultimately was performed in 19 of the 24 study participants.&lt;/p&gt;
&lt;p&gt;Of the 19 patients who underwent resection, six (32%) had pathologic complete responses. Chang reported that nine of 16 evaluable patients converted from N1 to N0 status following preoperative therapy, and 11 of 20 were downstaged from T3 to T2-T0.&lt;/p&gt;
&lt;p&gt;Median overall survival for the patients was 47.7 months. The 56% five-year survival applied to patients in the first three dosing levels. Patients who received the highest dose have not been followed long enough to determine five-year survival.&lt;/p&gt;
&lt;p&gt;During the discussion that followed the presentation, Jaffer Ajani, MD, of M.D. Anderson Cancer Center in Houston, cited concerns about the treatment-related deaths and complexity of the regimen.&lt;/p&gt;
&lt;p&gt;&quot;This is a very big production; it&apos;s not simple to do,&quot; said Ajani. &quot;You have to have a gastroenterologist available to inject every week.&quot;&lt;/p&gt;
&lt;p&gt;&quot;Your numbers are very small, and the pathological CR rate is no different than any other reported in even larger trials,&quot; he added. &quot;And then the subgroups with survival, I&apos;m not sure how meaningful that is because your numbers are so small.&quot;&lt;/p&gt;
&lt;p&gt;Responding to the concern about treatment-related deaths, Chang said none of the deaths was related to the TNF injections.&lt;/p&gt;
&lt;p&gt;With regard to the survival data, he acknowledged the small size of the study and said, &quot;It is what it is.&quot;&lt;/p&gt;
&lt;p&gt;&quot;It appears, as an adjunct, to be safe, and given the preliminary data, I think it is encouraging enough to go on to a larger trial,&quot; said Chang. &quot;That is basically what we are saying. We have something interesting that warrants further study.&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;The study was supported by GenVec.&lt;/p&gt;&lt;p&gt;One or more investigators disclosed relationships with GenVec.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_196"
                     title="Adjuvant Therapy Improves Survival in Pancreatic Cancer (CME/CE)"
                     score="-0.002"
                     href="http://www.medpagetoday.com/Oncology/OtherCancers/tb/18039?impressionId=1265793737162"
                     
      &lt;p&gt;Adjuvant chemoradiotherapy significantly improves survival of patients with resectable pancreatic cancer, according to medical records of almost 3,000 patients.&lt;/p&gt;
&lt;p&gt;Chemoradiotherapy extended median survival by more than 30% compared with surgical resection only, researchers reported in the January &lt;em&gt;Archives of Surgery&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;&lt;em&gt; &lt;/em&gt;In a multivariate analysis, adjuvant chemoradiotherapy proved to be one of only three predictors of improved survival, the other two being treatment at high-volume and academic centers.&lt;/p&gt;
&lt;p&gt;&quot;This analysis provides strong evidence in a real-world setting that postoperative chemoradiotherapy and possibly adjuvant radiotherapy alone improve clinical outcome in patients with pancreatic cancer,&quot; Relin Yang, MD, of the University of Miami, and colleagues wrote.&lt;/p&gt;
&lt;p&gt;&quot;We further substantiate that this benefit is independent of the improved clinical outcomes obtained at high-volume centers and teaching facilities,&quot; they added.&lt;/p&gt;
&lt;p&gt;&quot;Nonetheless, this benefit remains modest, underscoring that further investigation is needed to establish a better adjuvant regimen after complete resection of pancreatic cancer.&quot;&lt;/p&gt;
&lt;p&gt;Complete surgical resection remains the only curative option for patients with early-stage pancreatic adenocarcinoma. Fewer than 25% of patients have cancer amenable to resection. For that small subset of patients, the role of adjuvant therapy remains controversial, the authors wrote.&lt;/p&gt;
&lt;p&gt;To address the issue, Yang and colleagues analyzed data from a population-based cancer registry. They augmented the data&apos;s predictive potential with information related to patient demographics, comorbidities, treatment, and type of facility.&lt;/p&gt;
&lt;p&gt;The authors identified 2,877 patients whose pancreatic adenocarcinoma was diagnosed and treated surgically with curative intent from 1998 to 2002. About 60% of the patients were older than 65. Some 90% were white (86.7% non-Hispanic), and 90% had no history of alcohol abuse.&lt;/p&gt;
&lt;p&gt;The authors reported that 51.9% of patients received neither chemotherapy nor chemoradiotherapy. About 25% received chemoradiotherapy, and another 10% received chemotherapy alone. Most patients were treated at low-volume centers (57.6%) and nonteaching facilities (72.8%).&lt;/p&gt;
&lt;p&gt;Median overall survival was 15 months, and 90-day postsurgical survival was 88.8%. Patients younger than 40 had the best survival (25.7 months versus 13.4 months for patients older than 65, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Race, ethnicity, and abstention from alcohol and tobacco did not significantly influence survival. Survival decreased as a patient&apos;s poverty level increased. Localized disease, well-differentiated tumors, and smaller tumor size were associated with significantly better survival (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Patients treated with surgery only had a significantly lower (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) median overall survival of 12.6 months compared with patients who received chemotherapy or radiation preoperatively (19.9 months) or postoperatively (17.0 months).&lt;/p&gt;
&lt;p&gt;Median survival was 18.2 months among patients treated at high-volume centers versus 13.1 months at low-volume centers (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001). Treatment at a teaching facility was associated with a median survival of 19.8 months compared with 13.6 months for nonteaching facilities (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Multivariate analysis correcting for comorbidities showed that postoperative chemoradiotherapy significantly reduced the mortality hazard ratio (HR 0.69, &lt;em&gt;P&lt;/em&gt;=0.04). The reduced hazard exceeded the benefit associated with treatment at a high-volume center (HR 0.85, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) or at a teaching facility (HR 0.84, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) and was independent of facility type.&lt;/p&gt;
&lt;p&gt;The authors confirmed findings from other studies showing a beneficial effect of treatment in high-volume and teaching facilities, and a benefit for all patients who receive adjuvant chemoradiotherapy, Nita Ahuja, MD, of Johns Hopkins, wrote in a commentary.&lt;/p&gt;
&lt;p&gt;However, the study had several prominent weaknesses: missing information on cancer stage in more than 50% of patients, unknown margin status, and no information on the type or duration of adjuvant therapy.&lt;/p&gt;
&lt;p&gt;The study also did not address another major controversy involving adjuvant therapy for pancreatic cancer.&lt;/p&gt;
&lt;p&gt;&quot;At the end of the day, the present study will do little to quell the debate over the relative benefits of adjuvant chemoradiotherapy compared with chemotherapy alone after surgical resection of pancreatic cancer,&quot; Ahuja wrote.&lt;/p&gt;
&lt;p&gt;North Americans have a bias toward adjuvant chemoradiotherapy, supported primarily by data from a single small randomized clinical trial and several retrospective studies, Ahuja continued. European clinicians favor adjuvant chemotherapy based on one large clinical trial showing a benefit for chemotherapy and another showing no survival advantage for chemoradiotherapy.&lt;/p&gt;
&lt;p&gt;&quot;The present study will do little to change the minds of either camp,&quot; Ahuja concluded.&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;Neither Yang and co-authors nor Ahuja had any disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_223"
                     title="ASCO GI: Regimen Benefits Colon Cancer Patients of All Ages"
                     score="-0.003"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCOGI/tb/18076?impressionId=1265793737162"
                     
      ORLANDO -- Patients with early-stage colorectal cancer benefit from adjuvant chemotherapy with capecitabine (Xeloda) and oxaliplatin (Eloxatin) regardless of age, according to a new analysis of data from a large multicenter clinical trial.&lt;br&gt;
&lt;br&gt;Disease-free survival (DFS) at three years increased from 60% with a control regimen to 66% with the capecitabine/oxaliplatin (XELOX) regimen among patients 70 or older.&lt;br&gt;
&lt;br&gt;Younger patients had a 3% absolute improvement in three-year DFS when treated with the regimen (72% versus 69% for the control group).&lt;br&gt;
&lt;br&gt;Similar results emerged from an analysis that used 65 as the age cutpoint, according to a presentation at a press briefing prior to the 2010 Gastrointestinal Cancers Symposium.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;&quot;XELOX is a new standard of care for patients with early colon cancer, regardless of age,&quot; said Daniel G. Haller, MD, of the University of Pennsylvania. &quot;Patients receiving XELOX immediately after surgery live disease-free for longer, and there is a trend towards superior overall survival with XELOX.&quot;&lt;/p&gt;
&lt;p&gt;The results contradict those of other recent studies that showed no survival benefit with the XELOX regimen in older patients. The reasons for the contradictory findings have yet to be determined, said Haller.&lt;/p&gt;
&lt;p&gt;The findings came from a subgroup analysis of the NO16968 trial. It compared XELOX with bolus intravenous 5-FU/leucovorin, which was the standard of care for stage III colon cancer when the trial began.&lt;/p&gt;
&lt;p&gt;The analysis was performed after two studies reported last year showed that the survival benefit of the regimen was limited to younger patients (&lt;em&gt;ASCO&lt;/em&gt; 2009. Abstract 4010, &lt;em&gt;J Clin Oncol&lt;/em&gt; 2009; 27: 3109-116).&lt;/p&gt;
&lt;p&gt;NO16968 involved a total 1,886 patients, including 409 patients who were ages 70 or older. Study participants were randomized to XELOX or the control regimen, and the primary endpoint was DFS.&lt;/p&gt;
&lt;p&gt;After a median follow-up of 57 months, the three-year DFS in patients younger than 70 was 72% with XELOX and 69% with the control regimen, representing a 21% reduction in the hazard ratio (95% CI 0.66 to 0.94).&lt;/p&gt;
&lt;p&gt;Among older patients, the 6% absolute difference in DFS favoring XELOX constituted a 13% reduction in the hazard ratio (95% CI 0.63 to 1.18).&lt;/p&gt;
&lt;p&gt;When the definition of &quot;older&quot; patients was 65 and older, XELOX still resulted in a 6% absolute difference in DFS compared with the control regimen (68% versus 62%, HR 0.81, 95% CI 0.64 to 1.03). Among patients younger than 65, XELOX led to a three-year DFS of 72% versus 69% with 5FU and leucovorin (HR 0.80, 95% CI 0.65 to 0.98).&lt;/p&gt;
&lt;p&gt;In response to a question, Haller acknowledged that the DFS difference in older patients did not achieve statistical significance, but he said the principal objective of the study was to examine the data for evidence of trends.&lt;/p&gt;
&lt;p&gt;Overall survival data were not sufficiently mature to perform definitive analyses. However, Haller said the data demonstrated trends in favor of XELOX for all age groups evaluated.&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;Haller disclosed relationships with sanofi-aventis and Hoffmann-La Roche.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_2_363"
                     title="SABCS: Pregnancy May Dampen Breast Cancer Survival"
                     score="-0.005"
                     href="