TREATMENT Pancreatic Cancer RESECTABLE DISEASE
Approximately 10% of patients present with localized nonmetastatic disease that is potentially suitable for surgical resection. Approximately 30% of patients have R1 resection (microscopic residual disease) following surgery. Those who undergo R0 resection (no microscopic or macroscopic residual tumor) and who receive adjuvant treatment have the best chance of cure, with an estimated median survival of 20–23 months and a 5-year survival of approximately 20%. Outcomes are more favorable in patients with small (<3 cm), well-differentiated tumors and lymph node–negative disease.
Patients should have surgery in dedicated pancreatic centers that have lower postoperative morbidity and mortality rates. The standard surgical procedure for patients with tumors of the pancreatic head or uncinate process is a pylorus-preserving pancreaticoduodenectomy (modified Whipple’s procedure). The procedure of choice for tumors of the pancreatic body and tail is a distal pancreatectomy, which routinely includes splenectomy.
Postoperative treatment improves long-term outcomes in this group of patients. Adjuvant chemotherapy comprising six cycles of gemcitabine is common practice worldwide based on data from three randomized controlled trials (Table 42-1). The Charité Onkologie trial (CONKO 001) found that the use of gemcitabine after complete resection significantly delayed the development of recurrent disease compared with surgery alone. The European Study Group for Pancreatic Cancer 3 (ESPAC-3) trial, which investigated the benefit of adjuvant 5-fluorouracil/folinic acid (5-FU/FA) versus gemcitabine, revealed no survival difference between the two drugs. However, the toxicity profile of adjuvant gemcitabine was superior to 5-FU/FA by virtue of its lower incidence of stomatitis and diarrhea. Adjuvant radiotherapy is not commonly used in Europe based on the negative results of the ESPAC-1 study. Adjuvant 5-FU-based CRT with gemcitabine before and after radiotherapy as used in the Radiation Therapy Oncology Group (RTOG) 97-04 trial is preferred in the United States. This approach may be most beneficial in patients with bulky tumors involving the pancreatic head. INOPERABLE LOCALLY ADVANCED DISEASE
Approximately 30% of patients present with locally advanced, unresectable, but nonmetastatic pancreatic carcinoma. The median survival with gemcitabine is 9 months. Patients who respond to chemotherapy or who achieve stable disease after 3–6 months of gemcitabine have frequently been offered consolidation radiotherapy. However, a large, phase III, randomized controlled trial, LAP-07, did not demonstrate any improvement in survival for patients treated with CRT after 4 months of disease control on either gemcitabine or a gemcitabine/erlotinib combination. METASTATIC DISEASE
Approximately 60% of patients with pancreatic cancer present with metastatic disease. Patients with poor performance status do not usually benefit from chemotherapy. Gemcitabine was the standard treatment with a median survival of 6 months and a 1-year survival rate of only 20%. The addition of nab-paclitaxel (an albumin bound nanoparticle formulation of paclitaxel) to gemcitabine results in significantly improved 1-year survival compared to gemcitabine alone (35% vs 22%, p <.001). Capecitabine, an oral fluoropyrimidine, has also been combined with gemcitabine (GEM-CAP) in a phase III trial that showed an improvement in response rate and progression-free survival over single-agent gemcitabine, but no overall survival benefit. However, pooling of two other randomized controlled trials with this trial in a meta-analysis resulted in a survival advantage with GEM-CAP. Addition of erlotinib, a small-molecule epidermal growth factor receptor inhibitor, produced a statistically significant but clinically marginal benefit when added to gemcitabine in the advanced disease setting. A phase III trial limited to good performance status patients with metastatic pancreatic cancer showed improved survival with the combination of 5-FU/FA, irinotecan, and oxaliplatin (FOLFIRINOX) compared with gemcitabine, but with increased toxicity (Table 42-2).