Surgery News - August 2007 - (Page 4)

ONCOLOGY Median Survival for Patients With Pancreatic Cancer 19 months SURGERY NEWS • A U G U S T 2 0 0 7 Only Surgery Can Cure the Disease Pancreatic Cancer • from page 1 surgery was successful in 96% and the tumors were deemed unresectable in the remaining 4%, the analysis showed. Median survival among patients who underwent surgery was significantly better, at 19 months, than the 8-month median survival observed in patients not offered the procedure. The 5-year survival rate in patients who underwent surgery was 19%, the authors noted. Logistic regression analysis of factors predicting use of surgery showed that patients were less likely to undergo surgery if they were older or black, if they had lower annual incomes, were less educated, or were receiving Medicare or Medicaid. “Patients were more likely to receive surgery at academic institutions, high-volume hospitals, and [National Comprehensive Cancer Network/National Cancer Institute] centers,” the authors wrote. While troublesome, the study’s findings “are no surprise at all,” according to Dr. Andrew L. Warshaw, surgeon-in-chief and chair of the surgery department at the Massachusetts General Hospital in Boston. “Pancreatic cancer is a tough disease, and not many people get cured given its relative frequency, so the physician population starts with a sense of nihilism that colors things greatly,” Dr. Warshaw said in an interview. “Even though surgery is the only cure for the disease at the present time, the surgery that is done for it is complex, and most surgeons don’t have substantial experience with it. The low volume increases the risk of a bad outcome and the sense that the surgery isn’t going to help.” Additionally, insurance companies and watchdog groups trumpet this message, he said, by discouraging the surgery by low-volume surgeons. For these reasons, “a lot of patients never even see a surgeon,” said Dr. Warshaw, an ACS Fellow. “Many primary care doctors, in effect, consider it good medical practice not to expose these patients to the surgery. It’s not uncommon for gastroenterologists to have jaundiced [pancreatic cancer] patients with bile duct obstruction and stent them and call it quits, rather than expose them [to pancreatectomy].” 8 months Pancreatectomy (n = 2,734) Source: Dr. Bilimoria No surgery (n = 6,825) For the surgeons’ part, “because many don’t do the Whipple procedure with much frequency, they subconsciously go in looking for reasons that it can’t be done, and they are ready to bail out fast by just doing a bypass or closing up and going home because they didn’t really want to be in there in the first place,” Dr. Warshaw noted. The message that is not being well dis- seminated through the medical ranks, however, “is that we’ve gotten a lot smarter about pancreatic cancer in recent years,” said Dr. Warshaw. “Thanks to advances in medical imaging, our tumor staging ability is much more precise, and we’ve come a long way in our ability to recognize less aggressive, more curable forms of tumors.” These changes have led to better patient selection for surgery, which, together with better trained surgeons, more referrals to centers of expertise, and improved perioperative care, has led to a greater number of pancreatic resections being performed. “Coincident with that, mortality related to surgery has fallen from about 25% in the early 80s to about 1% now,” Dr. Warshaw stated. “The challenge we face now is spreading this message through the medical ranks,” Dr. Warshaw added. Dr. Bilimoria and his colleagues stressed the need for the development of measures to improve the quality of pancreatic cancer care. Specifically, they wrote, “there is an opportunity to improve the care of pancreatic cancer patients in the United States by offering surgery to all appropriate patients with resectable disease.” ■ Melanoma Vaccine Fails to Curb Metastatic Disease BY BRUCE K. DIXON Else vier Global Medical Ne ws C H I C A G O — Patients with resected metastatic stage III or stage IV melanoma gained no overall benefit from a combination of bacillus Calmette-Guérin and allogeneic melanoma vaccine in an international, randomized, phase III trial, Dr. Donald L. Morton said at the annual meeting of the American Society of Clinical Oncology. Despite the vaccine’s disappointing showing, though, he is not throwing in the towel just yet and already is backing efforts to launch a new trial. In addition, he and his associates were encouraged by the trial’s unexpectedly high overall survival rate, compared with previous trials, said Dr. Morton, medical director and surgeon-in-chief at the John Wayne Cancer Institute in Santa Monica, Calif. The combined Malignant Melanoma Active Immunotherapy (MMAIT) trial was the first randomized multicenter trial to use surgical resection as initial therapy for stage IV melanoma patients with up to five metastatic sites. Over 1,600 patients with no evidence of residual disease following tumor resection were randomly and evenly assigned to one of two arms: bacillus Calmette-Guérin (BCG) plus allogeneic melanoma cell vaccine (MCV) or BCG plus placebo. There were two separate trials with 1,160 patients enrolled in the stage III melanoma trial (MMAIT 3) and 496 with stage IV disease into MMAIT 4. BCG was given as an immunologic adjuvant for the first two injections of both MCV (Canvaxin) and placebo, which thereafter were administered by intradermal injection every 2 weeks for the next three injections, every month for the remainder of the first year, every 2 months for the second year, and every 3 months for years 3, 4, and 5, said Dr. Morton, an ACS Fellow. On the basis of the recommendation of the independent data monitoring board, the study was terminated after the interim analysis because of the low probability of demonstrating significant improvement in survival of the BCG-plus-MCV arm if the study had continued to completion of follow-up and final analysis, he said. “To say we were surprised would be an understatement because, with the safety analysis, we were aware of the overall survival of the two groups and in stage III we had a new trial that would enter patients after the initial diagnosis of stage IV disease and then randomize to surgery plus adjuvant BCG, surgery plus observation, and best medical therapy,” Dr. Morton said. Calling the study “an impressive undertaking,” discussant Dr. Jeffrey S. Weber agreed that Canvaxin, which contains tumor cells, might suppress the immune system, which would account for the finding that overall survival was worse for both stage III and stage IV patients given the vaccine. “Did the cells express some counterregulatory molecules at their surface, or did they generate suppressive cytokines? Those are important questions that you want to think about,” said Dr. Weber, professor of interdisciplinary oncology at the H. Lee Moffitt Cancer Center in Tampa, Fla. Dr. Morton concluded that “Canvaxin with BCG does not appear to provide any benefit whatsoever in stage III and stage IV [no evidence of disease] melanoma patients and may even be detrimental. Resectable stage IV melanoma patients can have a long survival after surgery even with more than one site of resection, and even after a subsequent recurrence.” “For resectable stage IV melanoma, aggressive surgical resection is the standard of care in my practice,” he added. Dr. Morton believes it would be premature to dismiss the melanoma vaccine, noting that longThe survival rate was unexpectedly high in stage IV patients, especially those with M1a disease, Dr. Donald L. Morton said. term regression of evaluable disease is achieved in some patients. “We serially tested immune response with skin tests in 52% in the placebo group and 43% in the Canvaxin group. For those with M1b and M1c disease, overall survival was this trial and, again, confirming the John Wayne experience, the high responders had more favorable survival 39% and 36%, respectively. Also, among stage IV patients there was a large differ- than the poor responders, and with antibodies to urinary ence between median disease-free survival (8 months) and tumor-associated antigen we again see a 68% survival at 5 years in phase III versus 51% in nonresponders.” overall survival (36 months). In addition, delayed-type hypersensitivity response to “Our confirmation of prolonged survival in resected stage IV melanoma suggests that more widespread use Canvaxin correlated with improved survival in stage IV, of surgery is indicated at this stage of disease. The high and antibody response to urinary tumor-associated antisurvival may be due to the effectiveness of salvage gen was correlated with improved survival (stages III and surgery in patients who recur,” he said, adding that a IV), confirming the John Wayne trial data, Dr. Morton number of factors may explain the failure of the vaccine said. Dr. Morton owns stock in CancerVax, the maker of to improve survival. “BCG may be an active immunotherapy agent, or Canvaxin, and receives research funding from the comthere could have been selection bias. So we’ve proposed pany. ■ 63% alive at 5 years and at stage IV 40% were alive at 5 years,” Dr. Morton said. Disease-free survival slightly favored the Canvaxin arm, with 27% free of disease at 5 years versus 21% in the placebo arm; overall survival was slightly better (45% at 5 years) in the placebo arm, he explained. There was an unexpectedly high survival rate among patients with stage IV melanoma, especially among those with M1a disease, who made up 40% of the stage IV cohort. Among these patients, overall 5-year survival was BRUCE K. DIXON/ELSEVIER GLOBAL MEDICAL NEWS ELSEVIER GLOBAL MEDICAL NEWS

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Contents Drug Developments News From the College Thoracic Surgery Head & Neck Surgery

Surgery News - August 2007

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