<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_459"
                     title="Murtha Dead at 77"
                     score="0.011"
                     href="http://www.medpagetoday.com/Washington-Watch/Washington-Watch/tb/18388?impressionId=1265803281497"
                     
      &lt;p&gt;Representative John P. Murtha (D-Pa.), 77, long-time chairman of the House Appropriations Subcommittee on Defense, died yesterday afternoon from complications following a planned laparoscopic cholecystectomy, according to a statement from the congressman&apos;s office.&lt;/p&gt;
&lt;p&gt;He had been admitted to the intensive care unit at Virginia Hospital Center in Arlington on Jan. 31, days after surgeons at the National Naval Medical Center in Bethesda, Md., accidentally nicked his intestine during the operation, according to a report in &lt;em&gt;The Washington Post&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;In that same report, Rep. Bob Brady (D-Pa.), a close friend of Murtha&apos;s, said the congressman developed an infection and fever.&lt;/p&gt;
&lt;p&gt;Citing a request for privacy from the Murtha family and patient privacy laws, a spokesperson for the National Naval Medical Center declined to provide information on the operation.&lt;/p&gt;
&lt;p&gt;In a statement, Virginia Hospital Center said Murtha died &quot;despite aggressive critical care interventions.&quot;&lt;/p&gt;


  &lt;p&gt;Mark Malangoni, MD, surgeon-in-chief at MetroHealth Medical Center in Cleveland, told &lt;em&gt;MedPage Today&lt;/em&gt; that serious complications, including bowel damage and death, are not common following cholecystectomy. More complicated patients, such as the obese and diabetics, have a greater risk of complications and of a switch to an open procedure.&lt;/p&gt;
    &lt;p&gt;Death is extremely rare in healthy individuals, occurring in no more than one per 1,000 patients, according to the American College of Surgeons (ACS).
    &lt;p&gt;More common, but still infrequent, are bleeding and leakage of bile, both of which can be treated fairly easily, said Malangoni, a regent of the ACS.&lt;/p&gt;


&lt;p&gt;When the bowel is damaged, as reportedly occurred in Murtha&apos;s case, it typically occurs in two ways -- either from a sharp injury when the trocars used for a laparoscopic procedure are inserted or from a cautery burn.
    &lt;p&gt;Both types of injury can go unnoticed by the surgeon and may not become apparent for days after the operation, Malangoni said.&lt;p&gt;
    &lt;p&gt;Although he did not know the details of Murtha&apos;s case, Malangoni said a patient would usually be admitted right away, at least overnight, if the surgeon realized that an injury had occurred. The procedure likely would have switched from a laparoscopic one to an open one as well.&lt;/p&gt;


&lt;p&gt;A 2009 Cochrane Review comparing laparoscopic versus open cholecystectomy for patients with symptomatic cholecystolithiasis found no difference in mortality in 38 trials. No patients died in the laparoscopic group and only 0.09% died in the open group.&lt;/p&gt;
&lt;p&gt;Severe complications were reported in 2.2% of the laparoscopic patients and 6.8% of the open patients.&lt;/p&gt;


 &lt;p&gt;Malangoni said most surgeons become experienced with performing laparoscopic cholecystectomies before completing their residency; most will perform 40 or 50 by the end of training.&lt;p&gt;
    &lt;p&gt;&quot;It is a very common operation, so once out into practice, most general surgeons are doing dozens of these each year,&quot; he said. &quot;So your experience comes about pretty quickly.&quot;
    &lt;p&gt;It is unclear how much experience Murtha&apos;s surgeon had.&lt;/p&gt;

&lt;p&gt;Murtha had recently become the longest serving member of Congress in Pennsylvania state history.&lt;/p&gt;
&lt;p&gt;First elected in 1974, Murtha, a former Marine, was the first Vietnam War combat veteran to serve in Congress, and he served as an advocate for the military throughout his career. He was also a prominent critic of the Iraq War.&lt;/p&gt;
&lt;p&gt;Murtha is survived by his wife, Joyce, and three children.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_331"
                     title="Physicians Must Treat Transplant Tourists"
                     score="0.006"
                     href="http://www.medpagetoday.com/Gastroenterology/LiverTransplantation/tb/18203?impressionId=1265803281497"
                     
      &lt;p&gt;Patients who travel to foreign countries for organ transplants may return with more problems than they left with  --  and physicians here have a moral responsibility to treat them, researchers asserted in a transplant journal.&lt;/p&gt;
&lt;p&gt;&quot;Medical tourism&quot; has been on the rise as demand for organs outpaces supply and U.S. healthcare costs skyrocket, Thomas D. Schiano, MD, and Rosamond Rhodes, PhD, of Mount Sinai School of Medicine, reported in &lt;em&gt;Liver Transplantation&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Researchers have estimated that 300 medical tourism transplants occurred between 2004 and 2006, with more than 40% of transplant tourists residing in New York or California, which have only 18% of the total U.S. population. (See &lt;a href=&quot;http://www.medpagetoday.com/PublicHealthPolicy/HealthPolicy/12564&quot; mce_href=&quot;http://www.medpagetoday.com/PublicHealthPolicy/HealthPolicy/12564&quot; target=&quot;_blank&quot;&gt;International Medical Trade Turns Big Business&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;Yet physicians have had little guidance on delivering care to these patients, and some transplant centers may turn them away, based on their actions, Schiano and Rhodes wrote.&lt;/p&gt;
&lt;p&gt;Their questions about treatment arose with a 46-year-old Chinese patient who had been put on a waiting list for a liver transplant here because of end-stage liver disease.&lt;/p&gt;
&lt;p&gt;The patient waited on the list for a year as his disease progressed from 18 points to 21 points on a 40-point severity scale.&lt;/p&gt;
&lt;p&gt;Rather than wait any longer, the patient flew to China and had a liver transplant there.&lt;/p&gt;
&lt;p&gt;Many transplanted organs in China come from executed prisoners, raising concerns about disease. Also, foreign transplants may be compromised by poor organ matching, unhealthy donors, and post-transplant infections, while some transplant centers abroad may use substandard surgical techniques, the researchers said.&lt;/p&gt;
&lt;p&gt;Foreign centers are also less likely to send patients home with adequate records and education than centers here, they asserted.&lt;/p&gt;
&lt;p&gt;Three months after his transplant in China, the patient came back to the clinic at Mount Sinai for follow-up care because he was about to run out of imunosuppressive medication.&lt;/p&gt;
&lt;p&gt;Two months after that, the patient developed sepsis due to diffuse intrahepatic biliary stricturing related to hepatic artery thrombosis.&lt;/p&gt;
&lt;p&gt;He required three additional hospitalizations for biliary sepsis, and at that point, retransplantation was the only viable option, Schiano said.&lt;/p&gt;
&lt;p&gt;However, members of the medical team had conflicting views about giving the patient another new liver.&lt;/p&gt;
&lt;p&gt;&quot;He was a medically suitable candidate,&quot; Schiano and Rhodes wrote, &quot;but there was disagreement about whether it was morally right to provide him with a transplant.&quot;&lt;/p&gt;
&lt;p&gt;The clinicians had few ethical guidelines to refer to in making their decision because many deal solely with moral issues related to donors and foreign medical standards.&lt;/p&gt;
&lt;p&gt;For example, the International Society for Heart and Lung Transplantation issued a statement against accepting organs from prisoners in April 2007, and the American Association for the Study of Liver Diseases and the International Liver Transplant Society endorsed similar policies.&lt;/p&gt;
&lt;p&gt;The American Medical Association&apos;s guidelines on medical tourism focus on best practices  --  for example, the procedure must be voluntary, it can&apos;t limit the alternatives offered to patients, and patients should only be referred to accredited institutions.&lt;/p&gt;
&lt;p&gt;While the United Network for Organ Sharing (UNOS)&apos;s statement on medical tourism does maintain that the medical community has an obligation to provide care for these patients, it stops short of offering further direction to transplant programs.&lt;/p&gt;
&lt;p&gt;&quot;Little guidance is provided for dealing with the specific problems of patients who choose to become transplant tourists,&quot; Schiano and Rhodes wrote.&lt;/p&gt;
&lt;p&gt;Instead, they created some ethical guidance for the &quot;moral quandary.&quot;&lt;/p&gt;
&lt;p&gt;Physicians have a &quot;professional obligation to promote the good of patients&quot; as well as a &quot;professional responsibility to adhere to medicine&apos;s commitment to nonjudgmental regard,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;&quot;Taken together, the moral principles of beneficence and nonjudgmental regard direct us to treat potential or returning transplant tourists as we would treat other patients under our care by focusing on providing the medical treatment and support they need,&quot; they continued.&lt;/p&gt;
&lt;p&gt;Physicians shouldn&apos;t deny patients post-transplantation care, and they ought to provide emergent care at the very least. They may refer the patient to another transplant center for long-term follow-up if they regard it as unethical to continue treatment.&lt;/p&gt;
&lt;p&gt;Patients should also be informed about the possibility of transplant tourism when they are not eligible for a transplant in the U.S. or when they are likely to die before reaching the top of the transplant list, Schiano and Rhodes wrote.&lt;/p&gt;
&lt;p&gt;&quot;Patients should not be threatened with abandonment by a center&apos;s refusal to provide care upon their return,&quot; they added.&lt;/p&gt;
&lt;p&gt;As for the 46-year-old patient who was transplanted in China, the Mount Sinai team decided a transplant program must treat all patients on the basis of their need &quot;regardless of what they might have done or how they secured their transplant organ.&quot;&lt;/p&gt;
&lt;p&gt;&quot;Although [the patient] had a long, complicated transplantation course,&quot; they wrote, &quot;he is currently doing well.&quot;&lt;/p&gt;
&lt;p&gt;Mount Sinai has seen a total of nine patients who pursued transplants in China. Three of those had post-transplant problems but had been turned away elsewhere &quot;because several transplant centers in our region do not render care to transplant tourists,&quot; the authors wrote.&lt;/p&gt;
&lt;p&gt;Seven of those nine patients have hepatitis B. Another three had had a renal transplant in India, and subsequently developed liver failure, the authors reported.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_330"
                     title="Immune Cells Point to Skin Cancer Risk after Transplants (CME/CE)"
                     score="0.005"
                     href="http://www.medpagetoday.com/Nephrology/KidneyTransplantation/tb/18200?impressionId=1265803281497"
                     
      Monitoring two types of immune cells in kidney transplant recipients might identify patients with an increased risk of skin cancer, British investigators reported.&lt;br&gt;
&lt;br&gt;Increased levels of T-regulatory cells (Tregs) more than doubled the risk of squamous cell cancer of the skin. Decreased levels of natural killer (NK) cells were associated with more than a five-fold increased risk of skin cancer.&lt;br&gt;
&lt;br&gt;Both immune parameters had substantially greater predictive power than a history of squamous-cell skin cancer, according to an online report in the &lt;em&gt;Journal of the American Society of Nephrology&lt;/em&gt; by a team of Oxford University investigators.&lt;/p&gt;
&lt;p&gt;&quot;Squamous cell cancer of the skin affects about 30% of kidney transplant patients after 10 years of immunosuppression,&quot; Robert Carroll, MD, currently of Queen Elizabeth Hospital in Woodville, Australia, observed in a statement.&lt;/p&gt;
&lt;p&gt;&quot;A small number of patients develop multiple skin cancers per year, but there is no laboratory test to determine which transplant recipients will develop multiple skin cancers in the future.&quot;&lt;/p&gt;
&lt;p&gt;&quot;If a test can confirm high risk of skin cancer development, this may help clinicians to tailor immunosuppressive regimens for individual patients,&quot; he added.&lt;/p&gt;
&lt;p&gt;Long-term immunosuppression, such as that required for transplant recipients, confers an increased risk of squamous-cell skin cancer.&lt;/p&gt;
&lt;p&gt;Estimates of the magnitude have ranged as high as 200 times greater than the general population, the authors wrote. Additionally, 3% of organ transplant recipients require extensive plastic surgery each year as a result of skin cancer lesions.&lt;/p&gt;
&lt;p&gt;Age at transplantation and the immunosuppression dosage are the principal determinants of skin-cancer risk, and the dosage of immunosuppression also influences the risk of metastasis from squamous-cell cancer of the skin.&lt;/p&gt;
&lt;p&gt;In the general population, cancer has been associated with increased levels of Tregs, including CDR&lt;sup&gt;+&lt;/sup&gt;CD25&lt;sup&gt;high&lt;/sup&gt;FOXP3&lt;sup&gt;+&lt;/sup&gt; and CD8&lt;sup&gt;+&lt;/sup&gt;CD28&lt;sup&gt;-&lt;/sup&gt; cells. The same types of cells could play a role in the risk of skin cancer among organ transplant recipients, the authors wrote.&lt;/p&gt;
&lt;p&gt;Within the tumor microenvironment, Tregs may impair the antitumor activity of CD8&lt;sup&gt;+&lt;/sup&gt; and NK cell. However, in organ transplant recipients, Tregs help control or prevent rejections and may help improve long-term outcomes.&lt;/p&gt;
&lt;p&gt;Different immunosuppressive drugs affect Tregs differently, the authors continued. Sirolimus (Rapamune), for example, increases the number of FOXP3&lt;sup&gt;+&lt;/sup&gt; cells, whereas cyclosporine decreases Treg numbers.&lt;/p&gt;
&lt;p&gt;&quot;Tregs have not been assessed in relation to cancer after transplantation,&quot; the authors wrote. &quot;We therefore investigated the hypothesis that squamous-cell cancer in kidney transplant recipients would be associated with an increased number of Tregs.&quot;&lt;/p&gt;
&lt;p&gt;To examine the hypothesis, investigators phenotyped peripheral blood from 65 kidney transplant recipients with squamous skin cancer and 51 recipients without skin cancer, matched for age, sex, and duration of immunosuppression.&lt;/p&gt;
&lt;p&gt;They also quantified lymphocyte populations in skin cancer lesions from a subset of 25 patients and matched them with 25 other nontransplant patients with squamous cell cancer of the skin.&lt;/p&gt;
&lt;p&gt;The kidney transplant recipients had a median follow-up of 340 days. The investigators found that a concentration of &amp;gt;35 peripheral FOXP3&lt;sup&gt;+&lt;/sup&gt;CD4&lt;sup&gt;+&lt;/sup&gt;CD127&lt;sup&gt;low&lt;/sup&gt; regulatory T cells/&amp;#181;L was associated with a hazard ratio for squamous cell skin cancer of 2.48 (95% CI 1.04 to 5.98).&lt;/p&gt;
&lt;p&gt;An NK cell count &amp;lt;100 cells/&amp;#181;L was associated with a skin cancer hazard ratio of 5.6 (95% CI 1.31 to 24). A history of squamous cell cancer of the skin increased the risk of skin cancer recurrence by a third (HR 1.33, 95% CI 1.15 to 1.53).&lt;/p&gt;
&lt;p&gt;&quot;If similar immune phenotypes are predictive in other kidney transplant recipient populations, then immune phenotype method has the potential to inform immunosuppressive regimen manipulation in kidney transplant recipients at high risk for developing multiple squamous cell cancers,&quot; the authors 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;The authors had no relevant disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_307"
                     title="Good Results in Poor-Risk Rectal Cancer (CME/CE)"
                     score="0.002"
                     href="http://www.medpagetoday.com/HematologyOncology/ColonCancer/tb/18169?impressionId=1265803281497"
                     
      &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_260"
                     title="ASCO GI: Agent Targets IGF Receptor in Pancreatic Cancer (CME/CE)"
                     score="-0.001"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCOGI/tb/18124?impressionId=1265803281497"
                     
      &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>
</recommendedContent>