Extended cycle streptozotocin/5-FU chemotherapy for maintenance therapy in pancreatic neuroendocrine tumors

Endocrine. 2019 Aug;65(2):460-467. doi: 10.1007/s12020-019-01941-w. Epub 2019 Apr 29.


Purpose: The standard of care treatment for patients with advanced pancreatic neuroendocrine tumors (pNET) is a combination of streptozotocin and 5-FU. Although widely used, little is known about the best long-term strategy with these substances.

Methods: We here report our experience of 28 patients treated with streptozotocin/5-FU for advanced pNET with special consideration for long-term management using an extended cycle protocol.

Results: Standard 6-weekly Moertel protocol resulted in a median progression-free survival of 21 months (range 3-128) and a median overall survival of 69 months (range 3-157+) in the whole cohort. Thirteen of the 28 patients were switched to an extended 3-month cycle protocol for maintenance therapy. Of these 13 patients, 2 achieved complete remission, 1 partial remission, and 8 stable disease as best response while 2 showed progressive disease following switch to the extended protocol, resulting in an additional median progression-free survival of 23 months. Median overall survival after the start of chemotherapy in this patient group was 69 months (21-157+). Patients benefitted from extended periods free of chemotherapy-associated side effects after switching to the extended cycle protocol.

Conclusions: Switching to an extended cycle protocol of 3 months for maintenance therapy following initial standard cycles may achieve long-term disease stabilization in selected patients with advanced pNET with good patient acceptance.

Keywords: 5-FU; Chemotherapy; Neuroendocrine tumor; Streptozotocin.

MeSH terms

  • Antibiotics, Antineoplastic / administration & dosage*
  • Antimetabolites, Antineoplastic / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols
  • Female
  • Fluorouracil / administration & dosage*
  • Humans
  • Maintenance Chemotherapy
  • Male
  • Neuroendocrine Tumors / drug therapy*
  • Pancreatic Neoplasms / drug therapy*
  • Retrospective Studies
  • Streptozocin / administration & dosage*
  • Treatment Outcome


  • Antibiotics, Antineoplastic
  • Antimetabolites, Antineoplastic
  • Streptozocin
  • Fluorouracil