Resectable pancreatic cancer needs surgery, then chemotherapy

BMJ 2004; 328 doi: (Published 18 March 2004) Cite this as: BMJ 2004;328:661
  1. Scott Gottlieb
  1. New York

    Adjuvant chemotherapy has a significant survival benefit in patients with resected pancreatic cancer, whereas treatment with chemoradiotherapy has a negative effect on survival, the results of a new study, in the New England Journal of Medicine, show. The negative effect of chemoradiotherapy was thought to be due to the fact that it delayed the administration of chemotherapy.

    Pancreatic cancer, with an overall five year survival rate ranging from 0.4% to 4%, has a poor prognosis and is one of the top 10 causes of death from cancer in the Western world. Previous studies have shown that surgical resection improves survival, but only about 10% of patients with pancreatic cancer are eligible for the procedure, often because their disease has progressed too far.

    Adjuvant chemotherapy may improve long term survival, but its routine use is not universal because the results of randomised trials have been inconclusive. A previous study, the GITSG (Gastrointestinal Tumor Study Group) trial, randomly assigned 43 patients to receive surgery alone or surgery plus chemoradiotherapy followed by maintenance chemotherapy. The median survival was significantly longer in the “adjuvant treatment” group than in the surgery group (20 months v 11 months), with five year survival estimates of 18% and 8% respectively (Cancer 1987;59: 2006-10

    But three subsequent randomised studies failed to confirm the benefit of adjuvant treatment. Moreover, it is unclear whether the survival advantage in the GITSG trial was due to the combinationof chemoradiotherapy and maintenance chemotherapy or to only one of these treatments alone.

    In the new study, the European Study Group for Pancreatic Cancer (ESPAC) undertook a large, multicentre trial to compare the benefits of adjuvant chemoradiotherapy and maintenance chemotherapy alone in patients with pancreatic cancer (New England Journal of Medicine 2004;350: 1200-10).

    The researchers, led by Dr John Neoptolemos of the department of surgery, Liverpool University,randomly assigned 289 patients with resected pancreatic ductal adenocarcinoma to three different treatment regimes and one group to observation. Seventy three patients were treated with chemoradiotherapy alone (20 Gy over a two week period plus fluorouracil), 75 patients with chemotherapy alone (fluorouracil), and 72 patients with both chemoradiotherapy and chemotherapy. Sixty nine patients were observed.

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

    “The simplest explanation for these observations is that chemoradiotherapy delayed the administration of chemotherapy and consequently reduced the potential benefit of chemotherapy that is derived from delivering it as soon as possible after resection,” the authors wrote. “We conclude thatstandard care for patients with resectable pancreatic cancer should consist of curative surgery followed by adjuvant systemic chemotherapy.”

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