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 CancerThese 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) Chapter 089. Pancreatic Cancer (Part 4) Pancreatic Cancer: Treatment Symptoms and the associated impaired performance status are significantissues in the management of patients with pancreatic cancer, as they can have amarked negative impact on the ability to safely deliver chemotherapy or performcurative surgery. For example, patients with malabsorption secondary topancreatic insufficiency may be treated with pancreatic enzyme supplementation.Indeed effective symptom management is as important a therapeutic goal assurvival prolongation. Advanced Pancreatic Cancer These patients have metastatic or locally advanced inoperable disease andare the majority with newly diagnosed disease. Debulking surgery or partialresections have no role, as these procedures are associated with the same risks as acurative resection but are unlikely to improve survival. Many patients may,however, benefit from endoscopic biliary or duodenal stenting, and some patientsfrom nerve plexus blocks or ablation. Less frequently, intestinal bypass surgery isrequired. The deoxycytidine analogue gemcitabine, given as a single agent(gemcitabine 1000 mg/m2 weekly for 7 weeks followed by 1 week rest, thenweekly for 3 weeks every 4 weeks thereafter), has been the preferred treatment forthese patients since it was shown to yield clinical benefit (a composite parameterfor evaluating symptomatic benefit of treatment used in some trials of this disease)and improved survival compared to 5-fluorouracil. The median survival observedwith single-agent gemcitabine in randomized trials is about 6 months, with a 12-month survival of approximately 18%. Furthermore, two randomized trials haveshown improved survival from the addition of either the oral fluoropyrimidine,capecitabine (gemcitabine 1000 mg/m2 days 1, 8, and 15 plus capecitabine 1660mg/m2 days 1–21, repeated every 28 days), or the tyrosine kinase inhibitor of theepidermal growth factor receptor (EGFR), erlotinib (standard gemcitabine pluserlotinib 100 mg daily). The survival improvement observed with both of thesecombinations appears similar, and the addition of capecitabine to gemcitabine inthis regimen does not appear to increase the toxicity above single-agentgemcitabine. Either combination should, therefore, be considered as options fortreating these patients. Second-line treatment options in pancreatic cancer arelimited although there may be an emerging role for oxaliplatin-basedchemotherapy; fit patients who have failed first-line treatment should be offeredentry into clinical trials. On-going clinical trials are evaluating the potentialbenefits of incorporating other novel targeted agents into the treatment ofpancreatic cancer, usually together with gemcitabine. In patients with locally advanced unresectable disease, external beamchemoradiotherapy may be useful, either as initial treatment or as consolidationafter induction chemotherapy. Operable Disease Complete surgical resection in patients with localized disease (stage I or IIdisease), with distal metastases excluded by prior CT scan of the abdomen andpelvis, and CT of the chest or chest x-ray, is potentially curative. However, suchsurgery is only possible in 10–15% of patients, many of whom will suffer fromrecurrences of their disease. Indeed, the 5-year survival reported in randomizedtrials with surgery alone is approximately 10%, although modern series haveimproved on these results. Outcomes tend to be more favorable in patients withlymph node–negative disease, smaller tumors (less than 3 cm), negative resectionmargins and well-differentiated tumors. Despite a dismal long term outcome, thesepatients still have a better survival with surgery than with other palliativemeasures. Surgery is usually preceded by laparoscopy in order to exclude peritonealmetastases not seen on other staging investigations. Pancreaticoduodenectomy,also known as the Whipple procedure, is the standard operation for cancers of thehead or uncinate process of the pancreas. The procedure involves resection of thepancreatic head, duodenum, first 15 cm of the jejunum, common bile duct, andgallbladder, and a partial gastrectomy, with the pancreatic and biliary anastomosisplaced 45 to 60 cm proximal to the gastrojejunostomy. Perioperative mortalityrates have fallen to less than 5%, reflecting greater experience with the surgeryand perioperative management of these patients. However, this type of surgery ishighly specialized and should ideally only occur in dedicated centers with a highvolume of these cases and specialized surgeons. Adjuvant treatment for patients with curatively resected pancreatic cancer iscontroversial, with divergent treatment ...