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<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_467"
                     title="FDA Unveils New Safety Plan for Medical Imaging"
                     score="0.011"
                     href="http://www.medpagetoday.com/Radiology/DiagnosticRadiology/tb/18398?impressionId=1265799942693"
                     
      &lt;p&gt;WASHINGTON  --  The Food and Drug Administration (FDA) says it wants to issue new safety requirements for manufacturers of computed tomography (CT) and fluoroscopic devices to reduce unnecessary radiation from medical imaging.&lt;/p&gt;
&lt;p&gt;The FDA&apos;s plan focuses on three procedures with high radiation doses: CT, nuclear medicine studies, and fluoroscopy. These are the greatest contributors to total radiation exposure within the U.S. population, the FDA said. That&apos;s because they require much higher radiation doses than other radiographic procedures, such as standard X-rays, dental X-rays, and mammography.&lt;/p&gt;
&lt;p&gt;&quot;The amount of radiation Americans are exposed to from medical imaging has dramatically increased over the past 20 years,&quot; Jeffrey Shuren, MD, director of the FDA&apos;s Center for Devices and Radiological Health, said in a prepared statement. &quot;The goal of FDA&apos;s initiative is to support the benefits associated with medical imaging while minimizing the risks.&quot;&lt;/p&gt;
&lt;p&gt;While the three procedures have led to early diagnosis of disease, they expose patients to ionizing radiation that may increase lifetime cancer risk  --  although there is debate within the medical community about the extent of the danger.&lt;/p&gt;
&lt;p&gt;Radiologist Joseph Schoepf, MD, director of Cardiovascular Imaging at the Medical University of South Carolina, lauded the FDA&apos;s initiative and said it would restore the public&apos;s trust in imaging.&lt;/p&gt;
&lt;p&gt;&quot;It is important to note, however, that an increase in cancer mortality [from radiation] has not been observed,&quot; he added. &quot;On the contrary, cancer mortality has dramatically decreased over the past decades, in step with increased utilization of medical imaging.&quot;&lt;/p&gt;
&lt;p&gt;The &lt;em&gt;Archives of Internal Medicine &lt;/em&gt;recently published results from two studies indicating that &lt;a href=&quot;http://www.medpagetoday.com/Radiology/DiagnosticRadiology/17530&quot; mce_href=&quot;http://www.medpagetoday.com/Radiology/DiagnosticRadiology/17530&quot; target=&quot;_blank&quot; title=&quot;CT&amp;#8200;Scans&amp;#8200;May&amp;#8200;Deliver&amp;#8200;Higher-than-Expected&amp;#8200;Radiation&amp;#8200;Doses&quot;&gt;CT scans deliver much higher doses of radiation &lt;/a&gt;than previously thought. The FDA has noted that a patient would have to get 400 standard chest X-rays to be exposed to the same level of radiation as just one CT abdomen scan.&lt;/p&gt;
&lt;p&gt;In an accompanying editorial, the journal&apos;s editor, Rita Redberg, MD, wrote that the studies &quot;make us question if we have gotten carried away in our enthusiasm&quot; for CT.&lt;/p&gt;
&lt;p&gt;It&apos;s becoming clear, she said, that the large doses of radiation from CT scans will lead to additional cancers, which must be taken into account when physicians consider CT for their patients.&lt;/p&gt;
&lt;p&gt;By working with healthcare providers and other federal agencies, the FDA says it hopes to promote safer use of medical imaging and increase patient awareness of their radiation exposure. Part of that involves pushing providers to justify their radiation procedures and optimize the radiation dose in each one.&lt;/p&gt;
&lt;p&gt;&lt;span&gt;Schoepf, who serves on several American College of Radiology committees that discuss the proper used of various imaging procedures, approved of the FDA&apos;s goal but cautioned against restrictions that would hinder clinicians.&lt;/span&gt;&lt;/p&gt;
&lt;p&gt;&quot;There is indeed a need for enhanced transparency, better patient education, more dialogue between patients and their healthcare providers, and increased involvement of the patient in the decision process leading up to an imaging study,&quot; Schoepf said.&lt;/p&gt;
&lt;p&gt;&lt;span&gt;&quot;What is often forgotten in this discussion is that serious injury or death, resulting from missing a potentially life-threatening diagnosis if no imaging is performed, is a much greater, more imminent, and very real risk.&quot;&lt;/span&gt;&lt;/p&gt;
&lt;p&gt;In its statement, the FDA said it wants to boost efforts to develop at least one national registry of radiation doses that will capture information from a variety of imaging studies that can be used to establish benchmarks for healthcare facilities to use with patients.&lt;/p&gt;


 &lt;p&gt;Donald Frush, MD, a radiologist at Duke Medical Center and expert in CT radiation doses in children, said that radiation doses for CT examination vary widely, depending on the size of the patient and the body area scanned, among other things.&lt;/p&gt;
    &lt;p&gt;&quot;However, sometimes this variation is not necessary, and the dose may be excessive,&quot; Frush said.&lt;/p&gt;

&lt;p&gt;The ACR launched a similar registry about a year ago, according to spokesman Shawn Farley. The database is intended as a guide so a radiologist can quickly see how levels of radiation delivered in other practices and hospitals compare to what he or she is delivering.&lt;/p&gt;
&lt;p&gt;&quot;Now that the FDA has come out in favor of doing that, we&apos;re hoping that will put a little more weight behind the process and make more facilities want to take part in this,&quot; Farley told &lt;em&gt;MedPage Today. &lt;/em&gt;&lt;/p&gt;


 &lt;p&gt;Schoepf noted that European governments already require a permanent record of radiation exposure for each patient.&lt;/p&gt;
    &lt;p&gt;As a result, manufacturers of radiation equipment, most of whom sell their products in Europe, already have that capability, he said. So it shouldn&apos;t be difficult to implement the same standard in the U.S.&lt;/p&gt;
    &lt;p&gt;&quot;Radiation exposure should be no secret,&quot; Schoepf said.&lt;/p&gt;


&lt;p&gt;The FDA will hold a public meeting March 30 and 31 to hear comments on what types of safety requirements to establish for manufacturers of CT and fluoroscopic devices. Requirements might include: &lt;ul&gt; &lt;li&gt;That the radiation device display, record, and report equipment settings and radiation dose&lt;/li&gt; &lt;li&gt;Alerting users when the dose exceeds the optimal dose for most patients&lt;/li&gt; &lt;li&gt;Increased training for users&lt;/li&gt; &lt;li&gt;Ability to capture and transmit radiation dose information to a patient&apos;s electronic medical record in addition to national dose registries &lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;&lt;em&gt;This article was developed in collaboration with ABC News. &lt;/em&gt;&lt;img src=&quot;http://www.medpagetoday.com/upload/2009/10/1/14357_1.jpg&quot; mce_src=&quot;http://www.medpagetoday.com/upload/2009/10/1/14357_1.jpg&quot; alt=&quot;&quot;&gt;&lt;/p&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_260"
                     title="ASCO GI: Agent Targets IGF Receptor in Pancreatic Cancer (CME/CE)"
                     score="-0"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCOGI/tb/18124?impressionId=1265799942693"
                     
      &lt;p&gt;ORLANDO  --  A majority of patients with advanced pancreatic cancer had objective responses or stable disease when treated with an inhibitor of the insulin-like growth factor (IGF) receptor, according to data from a small clinical trial reported here.&lt;/p&gt;
&lt;p&gt;A fourth of patients had partial responses that lasted beyond 11 months in some cases. Another third had disease stabilization during treatment with the monoclonal antibody MK-0646, plus chemotherapy and erlotinib (Tarceva).&lt;/p&gt;
&lt;p&gt;&quot;We observed sustained partial responses with two different regimens,&quot; Milind Javle, MD, of M.D. Anderson Cancer Center in Houston, told attendees at the Gastrointestinal Cancers Symposium.&lt;/p&gt;
&lt;p&gt;&quot;Evaluation of MK-0646 is continuing in a randomized phase II study that will include correlative studies to identify predictive markers.&quot;&lt;/p&gt;
&lt;p&gt;Activation of the IGF-1 receptor is associated with an aggressive disease course in pancreatic cancer and acquired resistance to agents that target epidermal growth factor receptor (EGFR) such as erlotinib.&lt;/p&gt;
&lt;p&gt;&lt;/p&gt;
&lt;p&gt; &lt;/p&gt;
&lt;p&gt;Preclinical studies showed that combining an IGF-1 receptor antagonist and cetuximab (Erbitux) had synergistic activity against pancreatic cell lines, Javle said.&lt;/p&gt;
&lt;p&gt;MK-0646 preferentially binds IGF-1 receptor and not the insulin receptor. The antibody inhibits stimulation of IGF-1 receptor by both IGF-1 and IGF-2, Javle continued. MK-0646 downregulates expression of IGF-1 receptor in tumor models and has demonstrated antitumor activity in xenograft models.&lt;/p&gt;
&lt;p&gt;Phase I evaluation of MK-0646 as a single agent showed the antibody was well tolerated and led to downregulation of IGF-1 receptor and other molecules associated with tumor growth. Patients occasionally developed hyperglycemia, which was controlled with oral hypoglycemic agents.&lt;/p&gt;
&lt;p&gt;Javle reported data from a phase I-II study of MK-0646 in combination with gemcitabine (Gemzar) or gemcitabine plus erlotinib. The primary objective of the first phase was to determine the maximum tolerated dose of MK-0646 in combination therapy. Investigators assessed progression-free survival (PFS) of the two combination arms in the second phase.&lt;/p&gt;
&lt;p&gt;The study included patients with stage IV pancreatic adenocarcinoma at least six months after completion of adjuvant chemotherapy.&lt;/p&gt;
&lt;p&gt;Patients were enrolled in a nonrandomized, sequential manner to two treatment arms. One arm had a regimen consisting of weekly gemcitabine plus weekly MK-0646 at either 5 mg/kg or 10 mg/kg. In the second arm, patients received gemcitabine plus daily erlotinib and one of the two doses of MK-0646.&lt;/p&gt;
&lt;p&gt;Dose-limiting hematologic toxicity was defined as grade 4 thrombocytopenia, grade 4 neutropenia lasting at least seven days, or grade 3 or higher neutropenia with fever.&lt;/p&gt;
&lt;p&gt;Dose-limiting nonhematologic toxicity was defined as any grade 3-4 adverse event except rash and controlled hyperglycemia. Delayed dosing was defined as a delay of more than 14 days necessitated by toxicity.&lt;/p&gt;
&lt;p&gt;Of 28 patients enrolled in the study, 23 (82%) required dose adjustment of gemcitabine, and seven had toxicity-associated dose adjustments of erlotinib. Five patients discontinued erlotinib because of toxicity, but no patient withdrew from the study because of toxicity.&lt;/p&gt;
&lt;p&gt;The most frequent grade 3-4 nonhematologic toxicities were hyperglycemia and fatigue (five patients each) and elevated liver enzymes and hypermagnesemia (four each). Half the patients developed grade 3-4 neutropenia and five had grade 3-4 thrombocytopenia. No cases of febrile neutropenia occurred.&lt;/p&gt;
&lt;p&gt;Maximum tolerated dose (MTD) in the first arm was not reached at the 10 mg/kg dose of MK-0646. In the erlotinib arm, MTD was reached at the 5 mg/kg dose of MK-0646.&lt;/p&gt;
&lt;p&gt;Of 24 patients evaluable for response, six (25%) had partial responses and eight (33%) had stable disease. The remaining 10 patients had progressive disease. Response duration ranged from 14 to beyond 44 weeks. Time to progression did not differ between the treatment arms.&lt;/p&gt;
&lt;p&gt;A randomized phase II study of MK-0646 has already begun, said Javle. Patients receive one of three treatment regimens: gemcitabine plus the monoclonal antibody, with or without erlotinib, or control therapy with gemcitabine and erlotinib.&lt;/p&gt;
&lt;p&gt;The activity demonstrated in the study does not constitute an antitumor signal for MK-0646, Philip A. Philip, MD, of the Karmanos Cancer Center in Detroit, said during a formal discussion of the study.&lt;/p&gt;
&lt;p&gt;&quot;Further preclinical and clinical validation of and IGF-1 receptor-based multitargeted strategy in pancreatic cancer must be undertaken,&quot; he said. &quot;Additionally, predictive biomarkers must be developed for patient selection and stratification. We need more data before we begin to design a phase III study.&quot;&lt;/p&gt;
&lt;p&gt;Hyperglycemia with MK-0646 should not come as a surprise, Philip said. The IGF-1 receptor occurring on normal cells has 84% homology with insulin receptor.&lt;/p&gt;
&lt;p&gt;&quot;There will be overlap between IGF-1 receptor and insulin receptor when targeting IGF-1 receptor,&quot; said Philip. &quot;Moreover, up to 40% of patients with pancreatic cancer have diabetes mellitus.&quot;&lt;/p&gt;
&lt;p&gt;In an ongoing intergroup trial involving a different IGF-1 receptor inhibitor, almost half the patients developed grade 1 or 2 hyperglycemia, and 14% developed grade 3 or 4, he added. However, hyperglycemia does not appear to be a dose-limiting toxicity.&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 Merck.&lt;/p&gt;&lt;p&gt;One or more investigators in the study disclosed relationships with Merck.&lt;/p&gt;&lt;p&gt;Philip disclosed relationships with Bristol-Myers Squibb, ImClone, OSIP, sanofi-aventis, Genentech, Pfizer, Lilly, and Roche.&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"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCOGI/tb/18122?impressionId=1265799942693"
                     
      &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_256"
                     title="ASCO GI: Targeted Regimen Active in Esophageal Cancer"
                     score="-0.001"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCOGI/tb/18117?impressionId=1265799942693"
                     
      &lt;p&gt;Half of patients with metastatic esophageal cancer responded to a regimen of conventional chemotherapy and erlotinib (Tarceva), investigators in a small clinical trial reported here.&lt;/p&gt;
&lt;p&gt;Fifteen of 30 patients had objective responses, including one complete response, when the targeted agent was added to oxaliplatin (Eloxatin) and 5-FU (FOLFOX). The response rate exceeded prespecified efficacy criteria, which called for a 10% absolute improvement in historical response rates to oxaliplatin-based chemotherapy.&lt;/p&gt;
&lt;p&gt;&quot;We did not observe a high rate of grade 3-4 adverse events,&quot; Zev A. Wainberg, MD, of UCLA, said in an interview at the Gastrointestinal Cancers Symposium. &quot;With respect to the primary endpoint, we achieved what we set out to do, which was to achieve a response rate of 45%. We surpassed that with a 50% response rate.&quot;&lt;/p&gt;
&lt;p&gt;FOLFOX is a standard therapy for patients with metastatic gastric and esophageal cancer, but a rising incidence of adenocarcinoma of the gastroesophageal junction (GEJ) suggests a need for additional therapeutic options.&lt;/p&gt;
&lt;p&gt;Inhibitors of epidermal growth factor receptor, such as erlotinib, have demonstrated modest response rates in patients with esophageal/GEJ cancer but no evidence of activity against distal gastric cancer.&lt;/p&gt;
&lt;p&gt;Given that background, plus phase I evidence of the safety and tolerability of FOLFOX plus erlotinib, investigators designed a clinical trial to evaluate the combination in patients with untreated metastatic adenocarcinoma of the esophagus or GEJ. Patients enrolled in the phase II, single-arm study received a modified FOLFOX regimen consisting of oxaliplatin, 5-FU, and leucovorin, followed by more 5-FU. Additionally, patients received oral erlotinib daily.&lt;/p&gt;
&lt;p&gt;Treatment cycles were repeated every two weeks until disease progression, withdrawal, or unacceptable toxicity. The primary endpoint was overall response rate, with a goal of 10% improvement over a historical control rate of 34.8% with oxaliplatin-based regimens.&lt;/p&gt;
&lt;p&gt;Wainberg presented findings on 30 evaluable patients from the ongoing trial. The patients&apos; mean age was 59, all but three were men, six had unresectable cancer and the remaining 24 had metastatic disease. Four patients had prior surgery, and seven had received radiation or chemotherapy for nonmetastatic disease.&lt;/p&gt;
&lt;p&gt;In addition to the 50% overall response rate, 12 additional patients had stable disease, resulting in an overall disease control rate of 90%. The median progression-free survival was 5.1 months, and median overall survival was 11 months. Median follow-up duration was 7.5 months.&lt;/p&gt;
&lt;p&gt;The most common adverse events were diarrhea/dehydration (24%), hypokalemia (15%), neutropenia (9%), and elevated liver enzymes (9%). Wainberg said 86.5% of adverse events were grade 1-2. One patient died following gastrointestinal perforation, and 13 patients required interruptions or modifications in erlotinib dosing.&lt;/p&gt;
&lt;p&gt;&quot;To our knowledge, this is the first trial to selectively examine the addition of a targeted agent to chemotherapy in a clinically defined subset of upper GI cancers,&quot; Wainberg and colleagues concluded in a poster presentation.&lt;/p&gt;
&lt;p&gt;&quot;Based on these results, FOLFOX plus or minus erlotinib should be considered for further development,&quot; they added.&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;No funding source was reported for the study.&lt;/p&gt;&lt;p&gt;The authors had no disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_257"
                     title="ASCO GI: Targeted Agent Slows Neuroendocrine Tumors"
                     score="-0.001"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCOGI/tb/18116?impressionId=1265799942693"
                     
      &lt;p&gt;ORLANDO  --  Patients with progressive pancreatic neuroendocrine tumors lived twice as long without progression when treated with sunitinib (Sutent) compared with placebo, data from a French clinical trial showed.&lt;/p&gt;
&lt;p&gt;Median overall survival had not been reached in the sunitinib arm, but sunitinib treatment was associated with a 60% reduction in hazard ratio compared with placebo. More than 90% of patients in the sunitinib group remained alive at six months, Eric Raymond, MD, reported here at the Gastrointestinal Cancers Symposium.&lt;/p&gt;
&lt;p&gt;&quot;Sunitinib continuous daily dosing resulted in clinically significant improvement in the median progression-free survival (PFS), improvement in overall survival, and a clinically significant increase in overall response rate versus placebo,&quot; said Raymond, of Hopital Beaujon in Clichy, France.&lt;/p&gt;
&lt;p&gt;Most of the survival benefit owed to disease stabilization, as fewer than 10% of patients had objective responses.&lt;/p&gt;
&lt;p&gt;The finding suggests that sunitinib might facilitate use of second- and third-line therapies that could build on the delayed progression and extended survival, he added.&lt;/p&gt;
&lt;p&gt;Moreover, these findings appear to confirm results of phase I-II studies that showed sunitinib activity in pancreatic neuroendocrine tumors. In an open-label phase II study, for example, treatment with sunitinib led to partial responses in 16.7% of patients and stable disease &amp;#8805;6 months in 56.1%, and median time to progression of 7.7 months in 66 patients, Raymond said.&lt;/p&gt;
&lt;p&gt;Those favorable early benefits led to this multicenter phase III trial involving 170 patients, who received sunitinib 37.5 mg/d or placebo. Treatment continued until progression, death, withdrawal, and development of unacceptable toxicity. All patients also received best supportive care.&lt;/p&gt;
&lt;p&gt;The primary endpoint was progression-free survival. Secondary endpoints included overall survival, overall response rate, time to response, duration of response, safety, and patient-reported outcomes.&lt;/p&gt;
&lt;p&gt;The patients&apos; median age was 56, and 48% were men. All but one patient had ECOG 0-1 performance status. About half of the tumors were non-functioning. Among functioning tumors, gastrinomas accounted for 11%, other/multiple neuropeptide for about 8%, and unspecified for 22%.&lt;/p&gt;
&lt;p&gt;The median progression-free survival was 11.4 months in the sunitinib group and 5.5 months with placebo (HR 0.418, &lt;em&gt;P&lt;/em&gt;=0.0001). Patients treated with sunitinib had a 71.3% probability of being alive and free of disease at six months compared with 43.2% of the placebo group.&lt;/p&gt;
&lt;p&gt;Overall survival had not been reached after a median follow-up of 10 to 11 months. The probability of being alive at six months was 92.6% in the sunitinib arm and 85.2% in the placebo group. Kaplan-Meier analysis revealed a significant advantage in favor of the sunitinib arm (HR 0.409, &lt;em&gt;P&lt;/em&gt;=0.0204).&lt;/p&gt;
&lt;p&gt;Sunitinib was associated with an overall response rate of 9.3%, consisting of two complete responses and six partial responses. Additionally, 62.8% of patients in the sunitinib group had stable disease. The median response duration was 8.1 months. No objective responses occurred in the placebo group, but 60% had stable disease.&lt;/p&gt;
&lt;p&gt;Adverse events occurred more often in the sunitinib group, but grade 3+ events were uncommon in both groups.&lt;/p&gt;
&lt;p&gt;Although no unexpected adverse events were observed, Raymond said patients should be advised of the potential for graying of the hair, which occurred in almost 30% of sunitinib-treated patients.&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 Pfizer.&lt;/p&gt;&lt;p&gt;One or more investigators disclosed relationships with Pfizer.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
</recommendedContent>