Multi-center clinical evaluation of streptozocin-based chemotherapy for advanced pancreatic neuroendocrine tumors in Japan: focus on weekly regimens and monotherapy

Cancer Chemother Pharmacol. 2018 Oct;82(4):661-668. doi: 10.1007/s00280-018-3656-y. Epub 2018 Jul 27.


Purpose: Streptozocin (STZ) is a key agent for treating advanced pancreatic neuroendocrine tumors (pNET). Most STZ regimens for pNET are daily and also include 5-fluorouracil (5FU), whereas STZ monotherapy and weekly regimens have also been applied in daily practice in Japan. The present study aimed to evaluate responses to weekly regimens and to STZ monotherapy, and to identify a predictive marker of a response to STZ.

Methods: Clinical data regarding STZ-based chemotherapy for pNET were collected between 2015 and 2017 at 25 facilities. We analyzed the effects, safety, progression-free survival (PFS), and factors that correlate with responses to STZ.

Results: The overall objective response rate (ORR) of 110 patients who underwent STZ-based chemotherapy (monotherapy, 81.8%; weekly regimen 46.4%) was 21.8%, and PFS was 9.8 months. The ORR of weekly vs. daily regimens was 21.6 vs. 22.0% (P = 1.000), and that of monotherapy vs. combination therapy was 21.1 vs. 25.0% (P = 0.766). A Ki67 proliferation index (Ki67) of > 5% was a predictive marker of a response to STZ (P = 0.017), whereas regimen type, mono- or combination therapy, treatment line and liver tumor burden were not associated with responses. The frequencies of Grade ≥ 3 nausea and hematological adverse events were significantly lower for monotherapy than combination therapy (P = 0.032).

Conclusions: The effects of weekly STZ monotherapy on pNET are comparable to those previously reported and the toxicity profile was acceptable. Ki67 > 5% was the sole predictive marker of an objective response.

Keywords: Ki67 proliferation index; Monotherapy; Pancreatic neuroendocrine tumor; Prognostic factor; Streptozocin.

Publication types

  • Multicenter Study

MeSH terms

  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / adverse effects
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Humans
  • Japan
  • Ki-67 Antigen / analysis*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neuroendocrine Tumors* / blood
  • Neuroendocrine Tumors* / drug therapy
  • Neuroendocrine Tumors* / pathology
  • Pancreatic Neoplasms* / blood
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / pathology
  • Predictive Value of Tests
  • Progression-Free Survival
  • Retrospective Studies
  • Streptozocin* / administration & dosage
  • Streptozocin* / adverse effects
  • Treatment Outcome


  • Antibiotics, Antineoplastic
  • Ki-67 Antigen
  • MKI67 protein, human
  • Streptozocin