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

Ann Surg Oncol. 2018 Jun;25(6):1709-1715. doi: 10.1245/s10434-018-6468-8. Epub 2018 Apr 6.

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.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemotherapy, Adjuvant
  • Child
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / secondary
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Neuroendocrine Tumors / drug therapy*
  • Neuroendocrine Tumors / secondary
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Neoplasms / surgery
  • Preoperative Care
  • Streptozocin / administration & dosage
  • Survival Rate
  • Tumor Burden
  • Young Adult

Substances

  • Streptozocin
  • Doxorubicin
  • Fluorouracil