Chapter 089. Pancreatic Cancer (Part 4)

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Pancreatic Cancer: Treatment Symptoms and the associated impaired performance status are significant issues in the management of patients with pancreatic cancer, as they can have a marked negative impact on the ability to safely deliver chemotherapy or perform curative surgery. For example, patients with malabsorption secondary to pancreatic insufficiency may be treated with pancreatic enzyme supplementation. Indeed effective symptom management is as important a therapeutic goal as survival prolongation. Advanced Pancreatic Cancer These patients have metastatic or locally advanced inoperable disease and are the majority with newly diagnosed disease. ...

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Chapter 089. Pancreatic Cancer (Part 4) Pancreatic Cancer: Treatment Symptoms and the associated impaired performance status are significant issues in the management of patients with pancreatic cancer, as they can have a marked negative impact on the ability to safely deliver chemotherapy or perform curative surgery. For example, patients with malabsorption secondary to pancreatic insufficiency may be treated with pancreatic enzyme supplementation. Indeed effective symptom management is as important a therapeutic goal as survival prolongation. Advanced Pancreatic Cancer These patients have metastatic or locally advanced inoperable disease and are the majority with newly diagnosed disease. Debulking surgery or partial resections have no role, as these procedures are associated with the same risks as a
curative resection but are unlikely to improve survival. Many patients may, however, benefit from endoscopic biliary or duodenal stenting, and some patients from nerve plexus blocks or ablation. Less frequently, intestinal bypass surgery is required. The deoxycytidine analogue gemcitabine, given as a single agent (gemcitabine 1000 mg/m2 weekly for 7 weeks followed by 1 week rest, then weekly for 3 weeks every 4 weeks thereafter), has been the preferred treatment for these patients since it was shown to yield clinical benefit (a composite parameter for evaluating symptomatic benefit of treatment used in some trials of this disease) and improved survival compared to 5-fluorouracil. The median survival observed with single-agent gemcitabine in randomized trials is about 6 months, with a 12- month survival of approximately 18%. Furthermore, two randomized trials have shown improved survival from the addition of either the oral fluoropyrimidine, capecitabine (gemcitabine 1000 mg/m2 days 1, 8, and 15 plus capecitabine 1660 mg/m2 days 1–21, repeated every 28 days), or the tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR), erlotinib (standard gemcitabine plus erlotinib 100 mg daily). The survival improvement observed with both of these combinations appears similar, and the addition of capecitabine to gemcitabine in this regimen does not appear to increase the toxicity above single-agent gemcitabine. Either combination should, therefore, be considered as options for treating these patients. Second-line treatment options in pancreatic cancer are
limited although there may be an emerging role for oxaliplatin-based chemotherapy; fit patients who have failed first-line treatment should be offered entry into clinical trials. On-going clinical trials are evaluating the potential benefits of incorporating other novel targeted agents into the treatment of pancreatic cancer, usually together with gemcitabine. In patients with locally advanced unresectable disease, external beam chemoradiotherapy may be useful, either as initial treatment or as consolidation after induction chemotherapy. Operable Disease Complete surgical resection in patients with localized disease (stage I or II disease), with distal metastases excluded by prior CT scan of the abdomen and pelvis, and CT of the chest or chest x-ray, is potentially curative. However, such surgery is only possible in 10–15% of patients, many of whom will suffer from recurrences of their disease. Indeed, the 5-year survival reported in randomized trials with surgery alone is approximately 10%, although modern series have improved on these results. Outcomes tend to be more favorable in patients with lymph node–negative disease, smaller tumors (less than 3 cm), negative resection
margins and well-differentiated tumors. Despite a dismal long term outcome, these patients still have a better survival with surgery than with other palliative measures. Surgery is usually preceded by laparoscopy in order to exclude peritoneal metastases not seen on other staging investigations. Pancreaticoduodenectomy, also known as the Whipple procedure, is the standard operation for cancers of the head or uncinate process of the pancreas. The procedure involves resection of the pancreatic head, duodenum, first 15 cm of the jejunum, common bile duct, and gallbladder, and a partial gastrectomy, with the pancreatic and biliary anastomosis placed 45 to 60 cm proximal to the gastrojejunostomy. Perioperative mortality rates have fallen to less than 5%, reflecting greater experience with the surgery and perioperative management of these patients. However, this type of surgery is highly specialized and should ideally only occur in dedicated centers with a high volume of these cases and specialized surgeons. Adjuvant treatment for patients with curatively resected pancreatic cancer is controversial, with divergent treatment approaches preferred in the United States and in Europe, based on the results of different randomized trials conducted on both sides of the Atlantic. In the United States, fluoropyrimidine-based postoperative chemoradiotherapy followed by adjuvant chemotherapy is preferred. In Europe, because a large randomized trial (the European Study Group for Pancreatic Cancer 1 or ESPAC1 trial) showed a survival benefit for adjuvant
chemotherapy with 5-fluorouracil (5FU) (Fig. 89-2), this approach is more common practice.