management of pancreatic carcinoma

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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:

Last edited 04/2018 and last reviewed 03/2021

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