<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_307"
                     title="Good Results in Poor-Risk Rectal Cancer (CME/CE)"
                     score="0.005"
                     href="http://www.medpagetoday.com/HematologyOncology/ColonCancer/tb/18169?impressionId=1265746958198"
                     
      &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="0.003"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCOGI/tb/18122?impressionId=1265746958198"
                     
      &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_250"
                     title="Cancer Research &quot;Giant&quot; Lawrence Garfinkel Dies at 88"
                     score="0"
                     href="http://www.medpagetoday.com/Pulmonology/Smoking/tb/18108?impressionId=1265746958198"
                     
      &lt;p&gt;Epidemiologist Lawrence Garfinkel, MA, a legendary researcher for the American Cancer Society whose work helped establish a link between cancer and smoking and other activities, died of cardiovascular disease Thursday in Seattle, Washington at 88.&lt;/p&gt;
&lt;p&gt;&quot;The American Cancer Society today mourns the loss of one of its most important historical figures,&quot; said John R. Seffrin, PhD, the society&apos;s chief executive officer.&lt;/p&gt;
&lt;p&gt;&quot;Larry Garfinkel joined the American Cancer Society as a young scientist in 1947, and for more than four decades played an instrumental role in expanding knowledge of and reducing death from smoking.&quot;&lt;/p&gt;
&lt;p&gt;Garfinkel&apos;s 1982 Cancer Prevention Study-II (CPS-II) is the largest contemporary study of tobacco and mortality, with 1.2 million participants and 77,000 data-compiling volunteers across 50 states, the District of Columbia, and Puerto Rico.&lt;/p&gt;
&lt;p&gt;CPS-II uncovered the effects of lifestyle factors, such as obesity, alcohol consumption, medications, genetic elements, that affect cancer and other chronic diseases, the analysis of which still reveals important clues about cancer today.&lt;/p&gt;
&lt;p&gt;The study also found lung cancer mortality rates in women increased five-fold from data collected in the original Cancer Prevention Study, while cancer rates among non-smoking women remained the same. This information provided strong evidence that lung cancer was almost exclusively a disease found in smokers.&lt;/p&gt;
&lt;p&gt;Garfinkel was born on January 11, 1922 in Manhattan&apos;s Lower East Side and was raised in the South Bronx.&lt;/p&gt;
&lt;p&gt;He served in the army during World War II, where he was seriously injured in northern France in August, 1944.&lt;/p&gt;
&lt;p&gt;Ultimately, Garfinkel graduated from the City College of New York and received a Masters Degree from Columbia University. He also received several honorary doctorates.&lt;/p&gt;
&lt;p&gt;Garfinkel began work for the ACS in 1947.&lt;/p&gt;
&lt;p&gt;He assisted E. Cuyler Hammond, MD, and Daniel Horn, MD, in the first ACS prospective mortality study of 187,783 males in the late 1940&apos;s by coordinating much of the field work, including training thousands of ACS volunteers in data collection techniques.&lt;/p&gt;
&lt;p&gt;Garfinkel acted as the co-principal investigator of the larger Cancer Prevention Study I (CPS-I) in 1959. The study enrolled 1 million participants across 25 states and required over 68,000 volunteers to collect data.&lt;/p&gt;
&lt;p&gt;In the 1960s, he contributed to more than two dozen major papers on the relation between smoking and health. He was co-author of one of the first reports combining epidemiology with pathology and provided some of the first direct evidence of lung damage related to smoking.&lt;/p&gt;
&lt;p&gt;Garfinkel also contributed to issuance of the landmark 1964 Surgeon General&apos;s report on smoking and health.&lt;/p&gt;
&lt;p&gt;He was appointed director of ACS research in 1979 after Hammond&apos;s retirement.&lt;/p&gt;
&lt;p&gt;Garfinkel retired from the ACS in 1989. Over the course of his career, he had contributed to more than 100 journal articles.&lt;/p&gt;
&lt;p&gt;Richard D. Klausner, MD, then-director of the National Cancer Institute, said at the time: &quot;Few individuals have contributed as much to our present-day knowledge about the disease consequences of smoking.&lt;/p&gt;
&lt;p&gt;&quot;His remarkable achievement is an important reminder what a tremendous impact an individual can make, and inspires all of us to continue the fight against cancer.&quot;&lt;/p&gt;
&lt;p&gt;Garfinkel continued to volunteer with the ACS after his retirement and taught biostatistics at the New York University Dental School.&lt;/p&gt;
&lt;p&gt;He is survived by his brothers, Harold and Melvin; his sons, Martin and Herb; a daughter-in-law, Margaret Cary, and two grandchildren.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_248"
                     title="Continued Smoking Worsens Lung Cancer Prognosis (CME/CE)"
                     score="0"
                     href="http://www.medpagetoday.com/HematologyOncology/LungCancer/tb/18105?impressionId=1265746958198"
                     
      &lt;p&gt;It&apos;s never too late to stop smoking, even for smokers already diagnosed with lung cancer, a new analysis shows.&lt;/p&gt;
&lt;p&gt;A systematic review of published trials of smokers diagnosed with early stage lung cancer disclosed that patients who stopped smoking when diagnosed were about twice as likely to survive for five years as those who continued to smoke after diagnosis, wrote Amanda Parsons, PhD, a research fellow at the University of Birmingham in England, and colleagues in a paper published online Jan. 22 by &lt;em&gt;BMJ.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;Continuing smoking was associated with a significantly increased risk of all cause mortality (hazard ratio 2.94, 95% CI, 1.15 to 7.54) as well as increased risk of cancer recurrence (HR 1.86, 95% CI 1.01 to 3.41), they wrote.&lt;/p&gt;
&lt;p&gt;The authors extrapolated the benefit of smoking cessation from both the recurrence and mortality data, since none of the studies contained specific information on the &quot;effect of quitting smoking on cancer specific mortality or on development of a second primary tumor in non-small cell lung cancer.&quot;&lt;/p&gt;
&lt;p&gt;They used life table-modeling to come up with the estimate that 33% of smokers diagnosed with early stage NSCLC at age 65 would survive for five years if they continued to smoke, versus an estimated 70% among those who quit smoking after diagnosis.&lt;/p&gt;
&lt;p&gt;&quot;This review has found evidence that after lung cancer has been diagnosed, reductions in risk of developing a second primary or recurrence were associated with quitting within seven years, suggesting that, even at this stage the prognostic outlook can be improved by smoking cessation,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;Whether this observation can be explained by nicotine or by other components of tobacco smoke is unknown, but regardless of the exact mechanism of harm, the authors wrote, the findings &quot;support the hypothesis that continued smoking affects the behavior of a lung tumor.&quot;&lt;/p&gt;
&lt;p&gt;In an accompanying editorial, Tom Treasure, MD, a cardiothoracic surgeon at University College London, and psychiatrist Janet Treasure, PhD, also from University College, wrote that Parsons et al demonstrated that the impact of continued smoking is so large that both patients and &quot;those caring for them should be given this information because the potential benefit is great.&quot;&lt;/p&gt;
&lt;p&gt;There is one significant problem both for patients and doctors, the editorialists noted: &quot;Fewer than one in three patients with lung cancer survive even one year, so the patients likely to benefit are probably healthier to begin with. So, although the information is valuable, it&apos;s application may be limited.&quot;&lt;/p&gt;
&lt;p&gt;Discussing its limitations, the review&apos;s authors noted that it was based on data from 10 observational studies, which raises the &quot;possibility of uncontrolled confounding.&quot;&lt;/p&gt;
&lt;p&gt;Moreover, definitions of smoking &quot;abstinence were generally poor and only five of the 10 studies assigned patients to smoking categories on the basis of smoking status recorded at six months or more after diagnosis.&quot;&lt;/p&gt;
&lt;p&gt;Additionally, they noted, it appears that &quot;smokers with unfavorable prognostic factors were most likely to give up smoking, so that unadjusted estimates underestimated the benefits of quitting.&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 funded by the UK Center for Tobacco Control Studies, the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, and the National Institute for Health Research.&lt;/p&gt;&lt;p&gt;Parsons said she has been reimbursed by Pfizer, maker of varenicline (Chantix) and nicotine nasal spray and inhaler products (Nicotrol).&lt;/p&gt;&lt;p&gt;The editorial writers disclosed no competing interests.&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="-0.001"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCOGI/tb/18076?impressionId=1265746958198"
                     
      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>
</recommendedContent>