Surgery News- July 2008

J U LY 2 0 0 8 • SURGERY NEWS ONCOLOGY 7 Pancreatic Cancer Survival Doubles With Gemcitabine B Y P AT R I C E W E N D L I N G Else vier Global Medical Ne ws C H I C A G O — Adjuvant chemotherapy with gemcitabine doubled 5-year survival rates, compared with surveillance alone, in pancreatic cancer patients who underwent surgery with curative intent, according to final results from a phase III international trial. After 5 years of follow-up, 21% of patients who were given gemcitabine (Gemzar) for 6 months and 9% of patients who were not given gemcitabine after curative surgery were still alive. Gemcitabine increased disease-free survival as well as overall survival, and “should be the standard of care for adjuvant treatment of pancreatic cancer,” Dr. Helmut Oettle of Charité Medical University of Berlin said in a press conference at the annual meeting of the American Society of Clinical Oncology. An intent-to-treat analysis from the CONKO-001 (Charité ONKOlogie Clinical Studies in GI cancer) trial enrolled 368 patients at 88 academic and community oncology centers in Germany and Austria. All had resected pancreatic cancer but no prior radiation or chemotherapy. Karnofsky performance scores were at least 50%. Patients were randomized to receive adjuvant chemotherapy with six cycles of gemcitabine on days 1, 8, and 15 every 4 weeks (n = 186) or observation (n = 182). The intent-to-treat analysis was based on 179 and 175 patients, respectively. Median ages were 62 years in the gemcitabine arm and 61 years in the observation arm. A total of 86% of patients in both groups had T3-4 tumors, and 71% of patients in the gemcitabine arm and 73% in the observation arm were lymph node positive. Median overall survival significantly improved from 20.2 months with observation to 22.8 months with gemcitabine (hazard ratio 0.72, P = .005). Long-term survival was comparable for the gemcitabine group vs. the observation group at 1 year (72% vs. 72.5%), but improved 8.5% at 2 years (48.5% vs. 40%), 17% at 3 years (36.5% vs. 19.5%), and 12% at 5 years (21% vs. 9%), Dr. Ulf Neumann reported at the meeting on behalf of the CONKO-001 study group. Subgroup analyses showed a significant beneficial effect of gemcitabine in patients with R0 resections (22.8 vs. 20.3 months, HR 0.74) and T3-4 tumors (21 vs. 19 months, HR 0.74); and a nonsignificant trend toward improvement in those with R1 resections (22.1 vs. 14.1 months, HR 0.62) and T1-2 tumors (40.6 vs. 27 months, HR 0.58). The number of patients in the subgroups was too small to draw any con- clusions, said Dr. Neumann, who is also at Charité Medical University of Berlin. The study’s primary end point of disease-free survival remained as previously reported ( JAMA 2007;297:267-77), significantly improving from 6.9 weeks with ob- AFTER 5 YEARS OF FOLLOW-UP, 21% OF PATIENTS WHO WERE GIVEN GEMCITABINE FOR 6 MONTHS AFTER CURATIVE SURGERY WERE STILL ALIVE. servation to 13.4 weeks with gemcitabine (HR 0.55, P < .001). Subgroup analyses showed a significant beneficial effect of gemcitabine on diseasefree survival in patients with R0 and R1 resections, lymph node–negative and –positive tumors, as well as T1-2 and T3-4 tumors, all with P values below .05, Dr. Neumann said. Discussant Dr. Robert Wolff of the University of Texas M.D. Anderson Cancer Center, Houston, said the trial’s findings support gemcitabine as a community standard for adjuvant therapy and provide the best level 1 evidence for disease-free, median overall, and 5-year survival. But Dr. James Neifeld, who commented on the study, advised caution. “Results will need to be replicated in the U.S. before we should consider it standard of care here,” said Dr. Neifeld, an ACS Fellow and chairman of the surgery department at Virginia Commonwealth University, Richmond. Dr. Wolff acknowledged that the overall survival results aren’t much much better than those of other adjuvant therapies, and the results don’t apply to all patients who undergo up-front surgery, because some may not be resectable, some don’t recover from surgery, and some are metastatic at restaging, said Dr. Wolff, who disclosed relationships with Eli Lilly & Co., the maker of gemcitabine; Genentech; and Sanofi-Aventis. “Are we making any progress, despite better surgery and perioperative care, better imaging, and slightly better chemotherapy?” Dr. Wolff asked. The first results from CONKO-001 showed that postoperative gemcitabine was well tolerated; grades 3/4 toxicities occurred infrequently. Overall survival and toxicity were secondary end points of the study, which was supported in part by a grant from Lilly Deutschland. Dr. Neumann disclosed a consultant or advisory role with Lilly Oncology, Roche Pharmaceuticals, and Sanofi-Aventis. ■ Cisplatin Does Not Improve Anal Canal Cancer Outcomes B Y M A RY A N N M O O N Else vier Global Medical Ne ws did not improve overall or disease-free Cisplatin-baseda induction chemotherapy survival rates in randomized phase III trial assessing 644 patients with anal canal carcinoma, researchers reported. This strategy to debulk the tumor and perhaps to sensitize it to later chemoradiotherapy was not superior to standard mitomycinbased induction treatment, and in fact increased the need for colostomy, they said. Disease-free survival rates were 61% at 3 years after diagnosis and 54% at 5 years with cisplatin-based induction chemotherapy, compared with 67% at 3 years and 60% at 5 years with standard treatment. Overall survival rates were 76% at 3 years and 70% at 5 years with cisplatin, compared with 84% at 3 years and 75% at 5 years with standard treatment. None of these differences were statistically significant. The rates of colostomy were 16% at 3 years and 19% at 5 years with cisplatin, which was significantly higher (P = .02) than the 10% colostomy rate at both time periods with standard treatment, the investigators said ( JAMA 2008;299:1914-21). These results “clearly demonstrate the importance of conducting phase [III] trials to test hypotheses that appear to have merit,” said Dr. Jaffer A. Ajani of the University of Texas M.D. Anderson Cancer Center, Houston, and his coauthors. Five cooperative research groups participated in the study, which was coordinated by the Radiation Therapy Oncology Group. The investigators undertook the trial because cisplatin chemoinduc- tion had produced “encouraging” results in preclinical trials and small pilot studies. “We hypothesized that induction chemotherapy with fluorouracil and cisplatin would reduce the volume of the primary tumor, and that the ensuing concurrent chemoradiation (experimental group) would be more effective for local control and colostomy-free survival compared with traditional up-front concur- rent chemoradiation with fluorouracilmitomycin (control group),” they explained. Dr. Ajani and associates evaluated 320 subjects in the experimental group and 324 in the control group, after following them for a median of 2.5 years. Subjects had histologically documented squamous, basaloid, or cloacogenic carcinoma of the anal canal. The tumors were stage T2-T4 (mea- suring from 2 cm in diameter to large enough to invade adjacent organs) with a range of nodal status. Approximately 27% of patients had tumors larger than 5 cm, and 26% had positive nodes. Cisplatin-based treatment should be used only in a clinical trial setting or in patients unable to tolerate the combination of fluorouracil and mitomycin, the investigators concluded. ■ http://www.NashvilleSurg.com

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Surgery News- July 2008 Contents The 20/20 Vision: Health Reform Trauma: Airway Anchor News From the College: Jacobson Winner General Surgery: Worth the Trouble

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