Journal of Digestive Cancer Research

Korean Society of Gastrointestinal Cancer Research (대한소화기암연구학회)
권호 표지

Treatment for Metastatic Pancreatic Cancer

전이성 췌장암의 치료

  • Bo Young Lee (Pancreatobiliary Cancer Clinic, National Cancer Center) ;
  • Sang Myung Woo (Pancreatobiliary Cancer Clinic, National Cancer Center)
  • 이보영 (국립암센터 췌담도암클리닉) ;
  • 우상명 (국립암센터 췌담도암클리닉)
  • Received : 2018.12.05
  • Accepted : 2018.12.15
  • Published : 2018.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Pancreatic ductal adenocarcinoma is a dismal prognosis and 5th leading cause of cancer related death in Korea. A large proportion of patients are diagnosed at advanced or metastatic stage. Therefore systemic chemotherapy has become the mainstay of treatment for pancreatic cancer. For most patients advanced or metastatic pancreatic cancer that has a good Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1, we can recommend for FOLFIRINOX (leucovorin, 5-fluorouracil [5-FU], irinotecan and oxaliplatin) and gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel). Currently, steps towards improved therapeutic efficacy of palliative chemotherapy have been made by introducing these regimens. For patients with an ECOG PS of 2, gemcitabine monotherapy or S1 alone is recommended. The second-line therapy for patients initially treated with gemcitabine-based chemotherapy includes provide FOLFOX (leucovorin, 5-FU, and oxaliplatin), capecitabine plus oxaliplatin, and 5-FU plus liposomal irinotecan. The gemcitabine-based chemotherapy is a reasonable choice for patients treated with FOLFIRINOX. Currently, studies on selecting patients for biomarkers related to molecular biologic features of tumors are underway for the realization of precise medicine, and the development and verification of preclinical models for the development of new therapeutic agents are being carried out continuously.

Keywords

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016;66:7-30.
  2. Kamisawa T, Wood LD, Itoi T, Takaori K. Pancreatic cancer. Lancet 2016;388:73-85.
  3. Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. N Engl J Med 2014;371:1039-1049.
  4. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 2014;74:2913-2921.
  5. Yip D, Karapetis C, Strickland A, Steer CB, Goldstein D. Chemotherapy and radiotherapy for inoperable advanced pancreatic cancer. Cochrane Database Syst Rev 2006:Cd002093.
  6. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011;364:1817-1825.
  7. Sohal DPS, Kennedy EB, Khorana A, et al. Metastatic pancreatic cancer: ASCO clinical practice guideline update. J Clin Oncol 2018;36:2545-2556.
  8. Gourgou-Bourgade S, Bascoul-Mollevi C, Desseigne F, et al. Impact of FOLFIRINOX compared with gemcitabine on quality of life in patients with metastatic pancreatic cancer: results from the PRODIGE 4/ACCORD 11 randomized trial. J Clin Oncol 2013;31:23-29.
  9. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013;369:1691-1703.
  10. Kim H, Samuel S, Lopez-Casas P, et al. SPARC-independent delivery of nab-paclitaxel without depleting tumor stroma in patient-derived pancreatic cancer xenografts. Mol Cancer Ther 2016;15:680-688.
  11. Hidalgo M, Plaza C, Musteanu M, et al. SPARC expression did not predict efficacy of nab-paclitaxel plus gemcitabine or gemcitabine alone for metastatic pancreatic cancer in an exploratory analysis of the phase III MPACT trial. Clin Cancer Res 2015;21:4811-4818.
  12. Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the national cancer institute of canada clinical trials group. J Clin Oncol 2007;25:1960-1966.
  13. Herrmann R, Bodoky G, Ruhstaller T, et al. Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss group for clinical cancer research and the central European cooperative oncology group. J Clin Oncol 2007;25:2212-2217.
  14. Heinemann V, Boeck S, Hinke A, Labianca R, Louvet C. Meta-analysis of randomized trials: evaluation of benefit from gemcitabine-based combination chemotherapy applied in advanced pancreatic cancer. BMC Cancer 2008;8:82.
  15. Sohal DP, Mangu PB, Khorana AA, et al. Metastatic pancreatic cancer: American society of clinical oncology clinical practice guideline. J Clin Oncol 2016;34:2784-2796.
  16. Ueno H, Ioka T, Ikeda M, et al. Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol 2013;31:1640-1648.
  17. Oettle H, Riess H, Stieler JM, et al. Second-line oxaliplatin, folinic acid, and fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory pancreatic cancer: outcomes from the CONKO-003 trial. J Clin Oncol 2014;32:2423-2429.
  18. Gill S, Ko YJ, Cripps C, et al. PANCREOX: A randomized phase III study of 5-fluorouracil/Leucovorin with or without oxaliplatin for second-line advanced pancreatic cancer in patients who have received gemcitabine-based chemotherapy. J Clin Oncol 2016.
  19. Xiong HQ, Varadhachary GR, Blais JC, Hess KR, Abbruzzese JL, Wolff RA. Phase 2 trial of oxaliplatin plus capecitabine (XELOX) as second-line therapy for patients with advanced pancreatic cancer. Cancer 2008;113:2046-2052.
  20. Wang-Gillam A, Li CP, Bodoky G, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet 2016;387:545-557.
  21. Fendrich V, Langer P, Bartsch DK. Familial pancreatic cancerstatus quo. Int J Colorectal Dis 2014;29:139-145.
  22. Wang T, Wentz SC, Ausborn NL, et al. Pattern of breast cancer susceptibility gene 1 expression is a potential prognostic biomarker in resectable pancreatic ductal adenocarcinoma. Pancreas 2013;42:977-982.
  23. Kaufman B, Shapira-Frommer R, Schmutzler RK, et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol 2015;33:244-250.
  24. Fogelman DR, Wolff RA, Kopetz S, et al. Evidence for the efficacy of iniparib, a PARP-1 inhibitor, in BRCA2-associated pancreatic cancer. Anticancer research 2011;31:1417-1420.
  25. Bajor DL, Vonderheide RH. Cracking the stone: combination vaccination and CTLA-4 blockade in pancreatic cancer. J Immunother 2013;36:362-364.
  26. Zhang Y, Choi M. Immune therapy in pancreatic cancer: now and the future? Rev Recent Clin Trials 2015;10:317-325.
  27. Seifert M, Seifert G, Wolff-Vorbeck G, Langenmair E, Hopt UT, Wittel UA. Inducing a humoral immune response to pancreatic cancer antigen. Cell Immunol 2016;310:150-155.
  28. DeSelm CJ, Tano ZE, Varghese AM, Adusumilli PS. CAR T-cell therapy for pancreatic cancer. J Surg Oncol 2017;116:63-74.
  29. Roshani R, McCarthy F, Hagemann T. Inflammatory cytokines in human pancreatic cancer. Cancer Lett 2014;345:157-163.
  30. Waghray M, Yalamanchili M, Dziubinski M, et al. GM-CSF mediates mesenchymal-epithelial cross-talk in pancreatic cancer. Cancer Discov 2016;6:886-899.
  31. Melstrom LG, Salazar MD, Diamond DJ. The pancreatic cancer microenvironment: A true double agent. J Surg Oncol 2017;116:7-15.
  32. Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 2017;357:409-413.
  33. Kamerkar S, LeBleu VS, Sugimoto H, et al. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature 2017;546:498-503.
  34. Thompson H. US National Cancer Institute's new Ras project targets an old foe. Nat Med 2013;19:949-950.
  35. Van Cutsem E, van de Velde H, Karasek P, et al. Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer. J Clin Oncol 2004;22:1430-1438.
  36. Patricelli MP, Janes MR, Li LS, et al. Selective inhibition of oncogenic KRAS output with small molecules targeting the inactive state. Cancer Discov 2016;6:316-329.
  37. Provenzano PP, Cuevas C, Chang AE, Goel VK, Von Hoff DD, Hingorani SR. Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell 2012;21:418-429.
  38. Moreira L, Bakir B, Chatterji P, Dantes Z, Reichert M, Rustgi AK. Pancreas 3D Organoids: Current and future aspects as a research platform for personalized medicine in pancreatic cancer. Cell Mol Gastroenterol Hepatol 2018;5:289-298.