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The clinical outcomes of second-line chemotherapy in patients with advanced pancreatic cancer: a retrospective study

  • Jung, Hyun yeb (Department of Internal Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine) ;
  • Lee, Eun Mi (Department of Internal Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine)
  • Received : 2021.07.22
  • Accepted : 2021.09.14
  • Published : 2022.04.30

Abstract

Background: Despite recent advances in first-line chemotherapy for advanced pancreatic cancer, standard treatment after the failure of initial chemotherapy has not been established. Hence, we aimed to retrospectively analyze the clinical characteristics and outcomes of second-line chemotherapy in patients with advanced pancreatic cancer. Methods: We reviewed the clinical data of patients with advanced pancreatic cancer who underwent palliative chemotherapy at Kosin University Gospel Hospital between January 2013 and October 2020. Results: Among 366 patients with advanced pancreatic cancer who had received palliative chemotherapy, 104 (28.4%) underwent at least one cycle of second-line chemotherapy. The median age of the patients at the time of initiating second-line treatment was 62 years (interquartile range, 57-62 years), and 58.7% (61 patients) of them were male. The common second-line chemotherapy regimens were 5-fluorouracil (FU) plus leucovorin, irinotecan, and oxaliplatin (33 patients, 31.7%); gemcitabine/nab-paclitaxel (29, 27.9%), gemcitabine±erlotinib (13, 12.5%); and oxaliplatin and 5-FU/leucovorin (12, 11.5%). The median overall survival (OS) and progression-free survival were 6.4 months (95% confidence interval [CI], 4.5-8.6 months) and 4.5 months (95% CI, 2.7-6.3 months), respectively. In a multivariate analysis, poor performance status (PS) (hazard ratio [HR], 2.247; p=0.021), metastatic disease (HR, 2.745; p=0.011), and elevated carcinoembryonic antigen (CEA) levels (HR, 1.939; p=0.030) at the beginning of second-line chemotherapy were associated with poor OS. Conclusion: The survival outcome of second-line chemotherapy for advanced pancreatic cancer remains poor. However, PS, disease extent (locally advanced or metastatic), and CEA level may help determine patients who could benefit from second-line treatment.

Keywords

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020;70:7-30. https://doi.org/10.3322/caac.21590
  2. Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011;364:1817-25. https://doi.org/10.1056/NEJMoa1011923
  3. Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013;369:1691-703. https://doi.org/10.1056/NEJMoa1304369
  4. Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, 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 CanadaClinical Trials Group. J Clin Oncol 2007;25:1960-6. https://doi.org/10.1200/JCO.2006.07.9525
  5. Oettle H, Riess H, Stieler JM, Heil G, Schwaner I, Seraphin J, 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;32:2423-9. https://doi.org/10.1200/JCO.2013.53.6995
  6. Gill S, Ko YJ, Cripps C, Beaudoin A, Dhesy-Thind S, Zulfiqar M, et al. PANCREOX: a randomized phase III study of fluorouracil/leucovorin with or without oxaliplatin for second-line advanced pancreatic cancer in patients who have received gemcitabine-based chemotherapy. J Clin Oncol 2016;34:3914-20. https://doi.org/10.1200/JCO.2016.68.5776
  7. Wang-Gillam A, Li CP, Bodoky G, Dean A, Shan YS, Jameson 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;387:545-57. https://doi.org/10.1016/S0140-6736(15)00986-1
  8. Ramaswamy A, Parthiban S, Malhotra M, Kothari R, Goel A, Bhargava P, et al. Outcomes with second-line chemotherapy in advanced pancreatic cancers: a retrospective study from a tertiary cancer center in India. Indian J Cancer 2018;55:144-7. https://doi.org/10.4103/ijc.ijc_553_17
  9. Tsang ES, Wong HL, Wang Y, Renouf DJ, Cheung WY, Lim HJ, et al. Outcomes and characteristics of patients receiving second-line therapy for advanced pancreatic cancer. Am J Clin Oncol 2019;42:196-201. https://doi.org/10.1097/COC.0000000000000500
  10. Gransmark E, Bagenholm Bylin N, Blomstrand H, Fredrikson M, Avall-Lundqvist E, Elander NO. Real world evidence on second-line palliative chemotherapy in advanced pancreatic cancer. Front Oncol 2020;10:1176. https://doi.org/10.3389/fonc.2020.01176
  11. Nagrial AM, Chin VT, Sjoquist KM, Pajic M, Horvath LG, Biankin AV, et al. Second-line treatment in inoperable pancreatic adenocarcinoma: a systematic review and synthesis of all clinical trials. Crit Rev Oncol Hematol 2015;96:483-97. https://doi.org/10.1016/j.critrevonc.2015.07.007
  12. Rahma OE, Duffy A, Liewehr DJ, Steinberg SM, Greten TF. Second-line treatment in advanced pancreatic cancer: a comprehensive analysis of published clinical trials. Ann Oncol 2013;24:1972-9. https://doi.org/10.1093/annonc/mdt166
  13. Pelzer U, Schwaner I, Stieler J, Adler M, Seraphin J, Dorken B, et al. Best supportive care (BSC) versus oxaliplatin, folinic acid and 5-fluorouracil (OFF) plus BSC in patients for second-line advanced pancreatic cancer: a phase III-study from the German CONKO-study group. Eur J Cancer 2011;47:1676-81. https://doi.org/10.1016/j.ejca.2011.04.011
  14. Kim ST, Choi YJ, Park KH, Oh SC, Seo JH, Shin SW, et al. A prognostic model to identify patients with advanced pancreas adenocarcinoma who could benefit from second-line chemotherapy. Clin Oncol (R Coll Radiol) 2012;24:105-11. https://doi.org/10.1016/j.clon.2011.02.005
  15. Sinn M, Dalken L, Striefler JK, Bischoff S, Schweitzer N, Pelzer U, et al. Second-Line treatment in pancreatic cancer patients: who profits? Results from the CONKO Study Group. Pancreas 2016;45:601-5. https://doi.org/10.1097/MPA.0000000000000533
  16. Vienot A, Beinse G, Louvet C, de Mestier L, Meurisse A, Fein F, et al. Overall survival prediction and usefulness of second-line chemotherapy in advanced pancreatic adenocarcinoma. J Natl Cancer Inst 2017;109. doi: 10.1093/jnci/djx037.
  17. Hsu CC, Liu KH, Chang PH, Chen PT, Hung CY, Hsueh SW, et al. Development and validation of a prognostic nomogram to predict survival in patients with advanced pancreatic cancer receiving second-line palliative chemotherapy. J Gastroenterol Hepatol 2020;35:1694-703. https://doi.org/10.1111/jgh.14926
  18. Lee JE, Lee HS, Chung MJ, Park JY, Park SW, Song SY, et al. Analysis of clinical predictive factors affecting the outcome of second-line chemotherapy for gemcitabine-refractory advanced pancreatic cancer. Gut Liver 2020;14:135-43. https://doi.org/10.5009/gnl18419
  19. Colloca G. Performance status as prognostic factor in phase III trials of first-line chemotherapy of unresectable or metastatic pancreatic cancer: a trial-level meta-analysis. Asia Pac J Clin Oncol 2021 Jun 23 [Epub]. http://doi.org/10.1111/ajco.13598.
  20. Sohal D, Kennedy EB, Khorana A, Copur MS, Crane CH, Garrido-Laguna I, et al. Metastatic pancreatic cancer: ASCO clinical practice guideline update. J Clin Oncol 2018;36:2545-56. https://doi.org/10.1200/JCO.2018.78.9636
  21. Ducreux M, Cuhna AS, Caramella C, Hollebecque A, Burtin P, Goere D, et al. Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015;26(Suppl 5):v56-68. https://doi.org/10.1093/annonc/mdv295
  22. Kim JH, Lee SC, Oh SY, Song SY, Lee N, Nam EM, et al. Attenuated FOLFIRINOX in the salvage treatment of gemcitabine-refractory advanced pancreatic cancer: a phase II study. Cancer Commun (Lond) 2018;38:32. https://doi.org/10.1186/s40880-018-0304-1
  23. Portal A, Pernot S, Tougeron D, Arbaud C, Bidault AT, de la Fouchardiere C, et al. Nab-paclitaxel plus gemcitabine for metastatic pancreatic adenocarcinoma after FOLFIRINOX failure: an AGEO prospective multicentre cohort. Br J Cancer 2015;113:989-95. https://doi.org/10.1038/bjc.2015.328
  24. da Rocha Lino A, Abrahao CM, Brandao RM, Gomes JR, Ferrian AM, Machado MC, et al. Role of gemcitabine as second-line therapy after progression on FOLFIRINOX in advanced pancreatic cancer: a retrospective analysis. J Gastrointest Oncol 2015;6:511-5. https://doi.org/10.3978/j.issn.2078-6891.2015.041
  25. Viaud J, Brac C, Artru P, Le Pabic E, Leconte B, Bodere A, et al. Gemcitabine as second-line chemotherapy after FOLFIRINOX failure in advanced pancreatic adenocarcinoma: a retrospective study. Dig Liver Dis 2017;49:692-6. https://doi.org/10.1016/j.dld.2017.02.007
  26. Sarabi M, Mais L, Oussaid N, Desseigne F, Guibert P, De La Fouchardiere C. Use of gemcitabine as a second-line treatment following chemotherapy with FOLFIRINOX for metastatic pancreatic adenocarcinoma. Oncol Lett 2017;13:4917-24. https://doi.org/10.3892/ol.2017.6061