Management of pancreatic carcinoma

The management of pancreatic carcinoma includes the following:

• curative:
  
  
  • surgery offers the only possibility of cure and should be performed in specialist centres
  • surgical methods include
    • pancreaticoduodenectomy – for tumours associated with the head, neck, and uncinate process of the pancreas
      • involves resection of the proximal pancreas, along with the distal stomach, duodenum, distal bile duct, and gallbladder as an en bloc specimen
      • Intestinal continuity is restored via a gastrojejunostomy, choledochojejunostomy, pancreaticojejunostomy
      • morbidity can be as high as 40% following this procedure
    • distal pancreactomy – for tumours of the body and tail of the pancreas
    • NICE state (2):
      • if head of pancreas cancer, consider pylorus preserving resection if the tumour can be adequately resected.
      • consider standard lymphadenectomy rather than extended lymphadenectomy for people having head of pancreas resection.
  • neoadjuvant chemotherapy and chemoradiation
    • could be useful in patients with resectable tumors
    • the aim neoadjuvant therapy is to increase the incidence of R0 resections, downstage borderline resectable disease to allow resection, and reduce loco-regional recurrence.
    • resectable pancreatic cancer neoadjuvant chemotherapy, radiotherapy or chemoradiation should only be performed within clinical trials
      
      
  • adjuvant chemotherapy (2)
    • start adjuvant therapy as soon as they are well enough to tolerate all 6 cycles.
    • adjuvant gemcitabine plus capecitabine should be offered to people who have had sufficient time to recover after pancreatic cancer resection
      
    • consider adjuvant gemcitabine for people who are not well enough to tolerate combination chemotherapy
      
      
  • locally advanced pancreatic cancer
    • systemic combination chemotherapy should be offered to people with locally advanced pancreatic cancer who are well enough to tolerate it.
    • consider gemcitabine for people with locally advanced pancreatic cancer who are not well enough to tolerate combination chemotherapy.
    • consider capecitabine as the radiosensitiser when using chemoradiotherapy
      
      
  • metastatic pancreatic cancer
    • First-line treatment
      • FOLFIRINOX should be offered to people with metastatic pancreatic cancer and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
      • gemcitabine combination therapy should be considered for people who are not well enough to tolerate FOLFIRINOX
      • gemcitabine should be offered to people who are not well enough to tolerate combination chemotherapy
    • Second-line treatment
      • oxaliplatin-based chemotherapy should be considered as second-line treatment for people who have not had first-line oxaliplatin.
      • gemcitabine-based chemotherapy should be considered as second-line treatment for people whose cancer has progressed after first-line FOLFIRINOX
        
        
  • palliative:
  • useful in patients who are unwilling or not medically fit enough to undergo major pancreatic surgery
  • jaundice and associated itching can be relieved by procedures such as
    • endoscopic or percutaneous stenting
    • surgical intervention such as creation of a biliary diversion via a cholecystojejunostomy.
  • vomiting may be due to duodenal involvement and thus a gastroenterostomy may be necessary
  • pain relief is achieved using opiates and/or coeliac plexus block

Notes:

• FOLFIRINOX is a chemotherapy regimen for treatment of advanced pancreatic cancer. It is made up of the following four drugs:
  • FOL - folinic acid (leucovorin), a vitamin B derivative that modulates/potentiates/reduces the side effects of fluorouracil;
  • F - fluorouracil (5-FU), a pyrimidine analog and antimetabolite which incorporates into the DNA molecule and stops DNA synthesis;
  • IRIN - irinotecan (Camptosar), a topoisomerase inhibitor, which prevents DNA from uncoiling and duplicating; and
  • OX - oxaliplatin (Eloxatin), a platinum-based antineoplastic agent, which inhibits DNA repair and/or DNA synthesis
• for metastatic disease - chemotherapy
  • for patients with advanced disease, gemcitabine is a reasonable choice and is the standard chemotherapy. However, the overall treatment benefits are limited
    • among patients with locally advanced metastatic pancreatic adenocarcinoma, gemcitabine has been shown to improve outcomes compared with fluorouracil
      • the US Food and Drug Administration approved gemcitabine in 1996 as the first chemotherapeutic agent for patients with pancreatic cancer since its approval of fluorouracil
        • approval was based on the results of studies on advanced disease
        • in a randomized trial of gemcitabine vs fluorouracil as a first-line therapy in 126 patients with advanced or metastatic adenocarcinoma of the pancreas, the median survival for patients treated with gemcitabine was 5.7 months and 1-year survival was 18% compared with a median survival of 4.4 months and 1-year survival of 2% for patients treated with fluorouracil (P = .003) (5)
    • combinations of GEM and other cytotoxic agents (such as 5-FU or capecitabine, irinotecan, cis- or oxaliplatin) do not confer a significant advantage in survival
    • combination of 5-FU, irinotecan and oxaliplatin (FOLFIRINOX) have shown a significant improvement in the overall survival of patients with stage IV pancreatic cancer and can be considered as a novel therapeutic option for patients ≤75 years of age with a good PS (0 or 1) and a level of bilirubin ≤1.5 ULN (3)

Reference:

• (1) Bond-Smith G et al. Pancreatic adenocarcinoma. BMJ. 2012;344:e2476
• (2) NICE (February 2018). Pancreatic cancer
• (3) Seufferlein T et al. Pancreatic adenocarcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23 Suppl 7:vii33-40
• (4) Drugs and Therapeutics Bulletin (2003);41(5): 36-39
• (5) Burris HA, Moore MJ, Anderson J; et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15(6):2403-2413