Dose and schedule modification are required for long-term continuation of sunitinib in Japanese patients with advanced pancreatic neuroendocrine tumors

Cancer Chemother Pharmacol. 2018 Jan;81(1):163-169. doi: 10.1007/s00280-017-3482-7. Epub 2017 Nov 21.


Purpose: This study aimed to clarify the efficacy and safety of sunitinib in Japanese patients with pancreatic neuroendocrine tumors (PNET), especially by focusing on dose and schedule modification.

Methods: Sixteen patients with advanced PNET treated with sunitinib were reviewed retrospectively. Efficacy was evaluated by progression-free survival (PFS) and objective tumor response. Toxicity profile was assessed regularly. Correlation between relative dose intensity (RDI) and treatment period was also evaluated.

Results: The median PFS was 25.8 months, and the probability of PFS at 1-year was 92%. The objective response rate and clinical benefit rate were 44% and 69%, respectively. The common adverse drug reactions (ADRs) were hand-foot syndrome (88%), neutropenia (75%), leucopenia (75%), and diarrhea (63%). Due to the development of severe ADRs, 81% required dose reduction and 31% discontinued sunitinib treatment, respectively. Prolonged treatment period was significantly correlated with decreased RDI (Spearman r = - 0.57, P = 0.022). The median RDI among 9 patients whom continued sunitinib more than 1 year was 49%.

Conclusions: Sunitinib showed significant clinical benefit in Japanese patients with advanced PNET in the real-world clinical setting. Successful management of ADRs with appropriate dose reduction and interruption can enable long-term continuation of sunitinib.

Keywords: Pancreatic neuroendocrine tumors; Relative dose intensity; Sunitinib; Tyrosine kinases inhibitor.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Drug Administration Schedule
  • Female
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Neuroendocrine Tumors / drug therapy*
  • Neuroendocrine Tumors / pathology
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Progression-Free Survival
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Retrospective Studies
  • Sunitinib / administration & dosage*
  • Sunitinib / adverse effects
  • Sunitinib / therapeutic use*


  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Sunitinib