A Randomized Trial of Chemoradiotherapy and Chemotherapy after Resection of Pancreatic Cancer
John P. Neoptolemos, NEJM 2004;350:1200

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The median survival was 15.9 months among the 145 patients who were assigned to chemoradiotherapy and 17.9 months among the 144 patients who were not assigned to receive chemoradiotherapy.Two-year and five-year survival estimates were 29 percent and 10 percent, respectively, among patients who received chemoradiotherapy and 41 percent and 20 percent, respectively, among those who did not receive chemoradiotherapy.

The median survival was 20.1 months among the 147 patients who received chemotherapy and 15.5 months among the 142 patients who did not receive chemotherapy.. Two-year and five-year survival estimates were 40 percent and 21 percent, respectively, among patients who received chemotherapy and 30 percent and 8 percent, respectively, among patients who received no chemotherapy

Background The effect of adjuvant treatment on survival in pancreatic cancer is unclear. We report the final results of the European Study Group for Pancreatic Cancer 1 Trial and update the interim results.

Methods In a multicenter trial using a two-by-two factorial design, we randomly assigned 73 patients with resected pancreatic ductal adenocarcinoma to treatment with chemoradiotherapy alone (20 Gy over a two-week period plus fluorouracil), 75 patients to chemotherapy alone (fluorouracil), 72 patients to both chemoradiotherapy and chemotherapy, and 69 patients to observation.

Adjuvant Therapy

Chemoradiotherapy consisted of a 20-Gy dose to the tumor given in 10 daily fractions over a two-week period plus an intravenous bolus of fluorouracil (500 mg per square meter of body-surface area on each of the first three days of radiotherapy and again after a planned break of two weeks). Chemotherapy consisted of an intravenous bolus of leucovorin (20 mg per square meter), followed by an intravenous bolus of fluorouracil (425 mg per square meter) on each of 5 consecutive days every 28 days for six cycles. Combination therapy consisted of chemoradiotherapy followed by chemotherapy, both administered as described above.

Results The analysis was based on 237 deaths among the 289 patients (82 percent) and a median follow-up of 47 months (interquartile range, 33 to 62). The estimated five-year survival rate was 10 percent among patients assigned to receive chemoradiotherapy and 20 percent among patients who did not receive chemoradiotherapy (P=0.05). The five-year survival rate was 21 percent among patients who received chemotherapy and 8 percent among patients who did not receive chemotherapy (P=0.009). The benefit of chemotherapy persisted after adjustment for major prognostic factors.

Conclusions Adjuvant chemotherapy has a significant survival benefit in patients with resected pancreatic cancer, whereas adjuvant chemoradiotherapy has a deleterious effect on survival.