Many clinicians are familiar with the clinical presentation, diagnostics, and treatment options for patients with pancreatic ductal adenocarcinoma. Periampullary adenocarcinoma represents a different clinical entity that is significantly less common than pancreatic ductal adenocarcinoma; however, patients can present with similar symptoms. The periampullary region consists of those organs within 2 cm of the ampulla of Vater, which includes the head of the pancreas, distal common bile duct, duodenum, or the ampulla of Vater itself. The overall incidence of periampullary carcinoma in the general population is relatively low, with rates of 11.7, 0.88, 0.49, and 0.01 per 100,000 in the pancreas, bile duct, ampulla, and duodenum respectively.1

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Up to 80% of all periampullary adenocarcinomas are resectable, which represents a significant treatment option for patients.2 The postsurgical resection 5-year survival rates vary based on location of the periampullary adenocarcinoma; however, it ranges from 23% to 59%.2 A challenging question that is often raised after surgical resection of any cancer is: What is the potential role of adjuvant chemotherapy with respect to survival benefit, quality of life, and symptomatic relief? There is significantly more data evaluating the role of adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma compared with those patients with periampullary adenocarcinoma. One of the more prominent studies that evaluated the role of adjuvant chemotherapy in periampullary adenocarcinoma was the European Study Group for Pancreatic Cancer (ESPAC)-3 periampullary trial.


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The ESPAC-3 trial was a prospective, open-label, phase 3, randomized controlled trial that included 100 centers and a total of 428 patients.2 All patients were evaluated postresection of their respective cancer, and the most common periampullary adenocarcinomas were the ampulla of Vater and bile duct. Patients were divided into one of three groups: observation, fluorouracil (FU) and folinic acid, or gemcitabine. The median survival in the observation group was 35.2 months compared with 43.1 months in the two treatment groups; however, these results were not statistically significant. Patients in the FU group had more statistically significantly adverse events compared with those patients in the gemcitabine group. The most common grade 3 or 4 toxicities included diarrhea, stomatitis, and fatigue. Therefore, the authors concluded that patients with resected periampullary adenocarcinomas who received adjuvant chemotherapy did not have a significant survival benefit when compared with observation. This study was somewhat limited by the relatively small patient population size, however; it was the largest randomized trial of its type at that time.

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Although it appears that there is no role for adjuvant chemotherapy in patients with resected periampullary adenocarcinomas with respect to survival, new data will hopefully continue to accumulate through clinical trials which may provide new options for these patients.

References

  1. Neoptolemos JP, Moore MJ, Cox TF, et al. Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial. JAMA. 2012;308(2):147-156.
  2. Berberat PO, Künzli BM, Gulbinas A, et al. An audit of outcomes of a series of periampullary carcinomas. Eur J Surg Oncol. 2009;35(2):187-191.