Pancreatic Cancer pp 1039-1071 | Cite as

Adjuvant Chemotherapy in Pancreatic Cancer

  • John P. Neoptolemos
  • David Cunningham
  • Francesco Sclafani
  • Paula Ghaneh
Reference work entry

Abstract

Pancreatic cancer is one of the major causes of cancer death. Most patients present with advanced disease, and only 10–15% of patients can undergo resection. Survival after curative surgery is poor, as recurrences occur either locally or distantly. Adjuvant therapy has been employed in large randomized trials to treat systemic disease and hopefully improve the poor prognosis. Chemoradiation, chemotherapy using 5-fluorouracil/folinic acid (5FU/FA), S-1, gemcitabine or gemcitabine plus capecitabine, and combination therapy have all been used in the adjuvant setting.

The results of the EORTC and ESPAC-1 trials have revealed that there is no survival advantage associated with adjuvant chemoradiation following resection for pancreatic cancer compared to no chemoradiation. There is no level 1 evidence, as yet that chemoradiation is superior to chemotherapy alone following surgery. Justification for the use of combination chemoradiation with follow-on chemotherapy is based on the results of an underpowered 1987 GITSG study, which closed prematurely and compared intervention to observation. The RTOG 9704 combination study did not demonstrate a survival difference between a 5FU-based regimen compared with a gemcitabine-based chemoradiation regimen. There is no completed randomized study comparing chemotherapy versus combination therapy.

There is a clear survival advantage with adjuvant 5FU/FA and single-agent gemcitabine based on the results from the ESPAC-1 and CONKO-001 study, respectively. The ESPAC-3 trial showed that these adjuvant regimens are equally effective, but gemcitabine has a better toxicity profile. In contrast, in a Japanese population, the JASPAC-01 trial demonstrated the superiority of S1 over gemcitabine. Adjuvant combination chemotherapy with gemcitabine plus capecitabine has been recently shown to provide a survival advantage compared with gemcitabine alone in Western patients in the ESPAC-4 trial. Phase III studies investigating other combination chemotherapy regimens are ongoing and will possibly increase the number of treatment options in this setting.

Keywords

Adjuvant chemotherapy Meta-analysis Pancreatic cancer Randomized controlled trial 

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • John P. Neoptolemos
    • 1
  • David Cunningham
    • 2
  • Francesco Sclafani
    • 2
  • Paula Ghaneh
    • 3
    • 4
  1. 1.Department of General, Visceral and Transplantation SurgeryUniversity of HeidelbergHeidelbergGermany
  2. 2.Department of MedicineThe Royal Marsden NHS Foundation TrustLondon and SurreyUK
  3. 3.Department of SurgeryThe Royal Liverpool and Broadgreen University Hospitals NHS TrustLiverpoolUK
  4. 4.Department of Molecular and Clinical Cancer MedicineInstitute of Translational Medicine, University of LiverpoolLiverpoolUK

Section editors and affiliations

  • James L. Abbruzzese
    • 1
  • Raul A. Urrutia
    • 2
  • John Neoptolemos
    • 3
  • Markus W. Büchler
    • 4
  1. 1.Duke University Medical CenterDurhamUSA
  2. 2.Mayo Clinic Cancer CenterMayo ClinicRochesterUSA
  3. 3.Division of Surgery and OncologyUniversity of LiverpoolLiverpoolUK
  4. 4.Department of General, Visceral and Transplantation SurgeryUniversity of HeidelbergHeidelbergGermany

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