Advertisement

Annals of Surgical Oncology

, Volume 25, Issue 6, pp 1709–1715 | Cite as

Preoperative Fluorouracil, Doxorubicin, and Streptozocin for the Treatment of Pancreatic Neuroendocrine Liver Metastases

  • Jordan M. Cloyd
  • Kiyohiko Omichi
  • Takashi Mizuno
  • Yoshikuni Kawaguchi
  • Ching-Wei D. Tzeng
  • Claudius Conrad
  • Yun Shin Chun
  • Thomas A. Aloia
  • Matthew H. G. Katz
  • Jeffrey E. Lee
  • Daniel Halperin
  • James Yao
  • Jean-Nicolas Vauthey
  • Arvind Dasari
Hepatobiliary Tumors

Abstract

Introduction

While preoperative chemotherapy is frequently utilized before resection of non-neuroendocrine liver metastases, patients with resectable neuroendocrine liver metastases typically undergo surgery first. FAS is a cytotoxic chemotherapy regimen that is associated with substantial response rates in locally advanced and metastatic pancreatic neuroendocrine tumors.

Methods

All patients who underwent R0/R1 resection of pancreatic neuroendocrine liver metastases at a single institution between 1998 and 2015 were included. The outcomes of patients treated with preoperative FAS were compared with those of patients who were not.

Results

Of the 67 patients included, 27 (40.3%) received preoperative FAS, whereas 40 (59.7%) did not. Despite being associated with higher rates of synchronous disease, lymph node metastases, and larger tumor size, patients who received preoperative FAS had similar overall survival [overall survival (OS), 108.2 months (95% confidence interval (CI) 78.0–136.0) vs. 107.0 months (95% CI 78.0–136.0), p = 0.64] and recurrence-free survival [RFS, 25.1 months (95% CI 23.2–27.0) vs. 18.0 months (95% CI 13.8–22.2), p = 0.16] as patients who did not. Among patients who presented with synchronous liver metastases (n = 46), the median OS [97.3 months (95% CI 65.9–128.6) vs. 65.0 months (95% CI 28.1–101.9), p = 0.001] and RFS [24.8 months (95% CI 22.6–26.9) vs. 12.1 months (2.2–22.0), p = 0.003] were significantly greater among patients who received preoperative FAS compared with those who did not.

Conclusions

The use of FAS before liver resection is associated with improved OS compared with surgery alone among patients with advanced synchronous pancreatic neuroendocrine liver metastases.

Notes

Acknowledgment

The authors recognize Ms. Ruth Haynes for administrative support in the preparation of this manuscript.

Disclosure

None of the authors have any conflicts of interest associated with this study.

Supplementary material

10434_2018_6468_MOESM1_ESM.docx (14 kb)
Supplementary material 1 (DOCX 13 kb)

References

  1. 1.
    Cloyd JM, Poultsides GA. Non-functional neuroendocrine tumors of the pancreas: advances in diagnosis and management. World J Gastroenterol. 2015;21(32):9512–25.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003;97(4):934–59.CrossRefPubMedGoogle Scholar
  3. 3.
    Touzios JG, Kiely JM, Pitt SC, et al. Neuroendocrine hepatic metastases: does aggressive management improve survival? Ann Surg. 2005;241(5):776–83.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Mayo SC, de Jong MC, Bloomston M, et al. Surgery versus intra-arterial therapy for neuroendocrine liver metastasis: a multicenter international analysis. Ann Surg Oncol. 2011;18(13):3657–65.CrossRefPubMedGoogle Scholar
  5. 5.
    Saxena A, Chua TC, Perera M, Chu F, Morris DL. Surgical resection of hepatic metastases from neuroendocrine neoplasms: a systematic review. Surg Oncol. 2012;21(3):e131–41.CrossRefPubMedGoogle Scholar
  6. 6.
    Fairweather M, Swanson R, Wang J, et al. Management of neuroendocrine tumor liver metastases: long-term outcomes and prognostic factors from a large prospective database. Ann Surg Oncol.2017.Google Scholar
  7. 7.
    Brouquet A, Abdalla EK, Kopetz S, et al. High survival rate after two-stage resection of advanced colorectal liver metastases: response-based selection and complete resection define outcome. J Clin Oncol. 2011;29(8):1083–90.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Kopetz S, Chang GJ, Overman MJ, et al. Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol. 2009;27(22):3677–83.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Martel G, Hawel J, Rekman J, et al. Liver resection for non-colorectal, non-carcinoid, non-sarcoma metastases: a multicenter study. PloS One. 2015;10(3):e0120569.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Broder LE, Carter SK. Pancreatic islet cell carcinoma. II. Results of therapy with streptozotocin in 52 patients. Ann Intern Med. 1973;79(1):108–18.CrossRefPubMedGoogle Scholar
  11. 11.
    Moertel CG, Hanley JA, Johnson LA. Streptozocin alone compared with streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma. N Engl J Med. 1980;303(21):1189–94.CrossRefPubMedGoogle Scholar
  12. 12.
    Moertel CG, Lefkopoulo M, Lipsitz S, Hahn RG, Klaassen D. Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med. 1992;326(8):519–23.CrossRefPubMedGoogle Scholar
  13. 13.
    Kouvaraki MA, Ajani JA, Hoff P, et al. Fluorouracil, doxorubicin, and streptozocin in the treatment of patients with locally advanced and metastatic pancreatic endocrine carcinomas. J Clin Oncol. 2004;22(23):4762–71.CrossRefPubMedGoogle Scholar
  14. 14.
    Rivera E, Ajani JA. Doxorubicin, streptozocin, and 5-fluorouracil chemotherapy for patients with metastatic islet-cell carcinoma. Am J Clin Oncol. 1998;21(1):36–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Prakash L, Bhosale P, Cloyd J, et al. Role of Fluorouracil, doxorubicin, and streptozocin therapy in the preoperative treatment of localized pancreatic neuroendocrine tumors. J Gastrointest Surg. 2017;21(1):155–63.CrossRefPubMedGoogle Scholar
  16. 16.
    Edge S, Byrd D, Compton C. AJCC Cancer Staging Manual, 7th edn. New York: Springer; 2010.Google Scholar
  17. 17.
    Dindo D, Demartines N, Clavien P-A. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Chu QD, Hill HC, Douglass HO, et al. Predictive factors associated with long-term survival in patients with neuroendocrine tumors of the pancreas. Ann Surg Oncol. 2002;9(9):855–62.CrossRefPubMedGoogle Scholar
  19. 19.
    Devata S, Kim EJ. Neoadjuvant chemotherapy with capecitabine and temozolomide for unresectable pancreatic neuroendocrine tumor. Case Rep Oncol. 2012;5(3):622–6.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Kaemmerer D, Prasad V, Daffner W, et al. Neoadjuvant peptide receptor radionuclide therapy for an inoperable neuroendocrine pancreatic tumor. World J Gastroenterol. 2009;15(46):5867–70.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Sowa-Staszczak A, Pach D, Chrzan R, et al. Peptide receptor radionuclide therapy as a potential tool for neoadjuvant therapy in patients with inoperable neuroendocrine tumours (NETs). Eur J Nucl Med Mol Imaging. 2011;38(9):1669–74.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    van Vliet EI, van Eijck CH, de Krijger RR, et al. Neoadjuvant treatment of nonfunctioning pancreatic neuroendocrine tumors with [177Lu-DOTA0,Tyr3] Octreotate. J Nucl Med. 2015;56(11):1647–53.CrossRefPubMedGoogle Scholar
  23. 23.
    Ezziddin S, Lauschke H, Schaefers M, et al. Neoadjuvant downsizing by internal radiation: a case for preoperative peptide receptor radionuclide therapy in patients with pancreatic neuroendocrine tumors. Clin Nucl Med. 2012;37(1):102–4.CrossRefPubMedGoogle Scholar
  24. 24.
    Stoeltzing O, Loss M, Huber E, et al. Staged surgery with neoadjuvant 90Y-DOTATOC therapy for down-sizing synchronous bilobular hepatic metastases from a neuroendocrine pancreatic tumor. Langenbecks Arch Surg. 2010;395(2):185–92.CrossRefPubMedGoogle Scholar
  25. 25.
    Sowa-Staszczak A, Hubalewska-Dydejczyk A, Tomaszuk M. PRRT as neoadjuvant treatment in NET. Recent Results Cancer Res Fortschritte Krebsforsch Progres Dans Rech Sur Cancer. 2013;194:479–85.CrossRefGoogle Scholar
  26. 26.
    Perysinakis I, Aggeli C, Kaltsas G, Zografos GN. Neoadjuvant therapy for advanced pancreatic neuroendocrine tumors: an emerging treatment modality? Horm Athens Greece. 2016;15(1):15–22.Google Scholar

Copyright information

© Society of Surgical Oncology 2018

Authors and Affiliations

  • Jordan M. Cloyd
    • 1
  • Kiyohiko Omichi
    • 1
  • Takashi Mizuno
    • 1
  • Yoshikuni Kawaguchi
    • 1
  • Ching-Wei D. Tzeng
    • 1
  • Claudius Conrad
    • 1
  • Yun Shin Chun
    • 1
  • Thomas A. Aloia
    • 1
  • Matthew H. G. Katz
    • 1
  • Jeffrey E. Lee
    • 1
  • Daniel Halperin
    • 2
  • James Yao
    • 2
  • Jean-Nicolas Vauthey
    • 1
  • Arvind Dasari
    • 2
  1. 1.Department of Surgical OncologyUniversity of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of Gastrointestinal Medical OncologyUniversity of Texas MD Anderson Cancer CenterHoustonUSA

Personalised recommendations