Adjuvant Chemo for Periampullary Adenocarcinoma Shows Modest Survival Benefit
The phase 3 open-label trial, the largest conducted in this population, enrolled 428 patients—297 with ampullary, 96 with bile duct, and 35 with other cancers—in 100 centers in Europe, Australia, Japan, and Canada from July 2000 to May 2008 and randomly assigned them to observation (n=144), folinic acid 20mg/m2 followed by fluorouracil 425mg/m2 days 1 to 5 every 28 days (n=143), or 1000mg/m2 gemcitabine once weekly for 3 of every 4 weeks (n=141) for 6 months, noted John P. Neoptolemos, MD, of the University of Liverpool, UK, on behalf of the European Study Group for Pancreatic Cancer.
Median survival was 35.2 months (95% CI, 27.2–43.0) in the observation group compared with 43.1 months (95%, CI, 34.0–56.0) in the two chemotherapy arms (HR 0.86; (95% CI, 0.66–1.11; Χ2=1.33; P=.25). After adjusting for independent prognostic variables and conducting multiple regression analysis, the hazard ratio for chemotherapy compared with observation was 0.75 (95% CI, 0.57–0.98; Wald Χ2=4.53, P=.03).
In the observation arm, 88 patients (61%) died, as did 83 (58%) in the fluorouracil and 73 (52%) in the gemcitabine arms.
“Based on the null hypothesis, the unadjusted primary analysis of the primary outcome of survival did not demonstrate a significant benefit for adjuvant chemotherapy. Multivariate analysis, correcting for prognostic variables, found a statistically significant survival benefit to chemotherapy and specifically for gemcitabine compared with observation, notwithstanding the better safety profile compared with fluorouracil plus folinic acid, but these results should be considered hypothesis generating,” the authors wrote.
“Although this study found support for the use adjuvant chemotherapy to improve survival in patients with periampullary cancers, this effect was modest, indicating a need for further improvements and warranting the testing of combination chemotherapies,” they concluded.