Ki67 proliferation index, hepatic tumor load, and pretreatment tumor growth predict the antitumoral efficacy of lanreotide in patients with malignant digestive neuroendocrine tumors

Eur J Gastroenterol Hepatol. 2013 Feb;25(2):232-8. doi: 10.1097/MEG.0b013e328359d1a6.

Abstract

Background: An antiproliferative effect of somatostatin analogs was recently demonstrated.

Aim: To identify factors associated with tumor control in a group of patients with well-differentiated malignant digestive neuroendocrine tumors treated with lanreotide.

Methods: A retrospective study was conducted in 68 patients treated with lanreotide alone, with progression-free survival as the primary endpoint. The role of the following factors was searched for by univariate and multivariate analyses: age, sex, mode of discovery, site of the primary tumor, metastatic spread, Ki67 proliferation index, uptake on somatostatin receptor scintigraphy, pretreatment tumor growth, extent of liver involvement, resection of primary tumor, previous treatments, and tumor markers.

Results: Tumor progression was observed in 39/68 patients (57.4%). Median progression-free survival was 29 months. On multivariate analysis, a Ki67 proliferation index of up to 5% [hazard ratio (HR)=0.262, P=0.009], pretreatment stability (HR=0.241, P=0.008), and hepatic tumor load of up to 25% (HR=0.237, P=0.004) were significantly associated with disease stability under lanreotide therapy.

Conclusion: In patients with well-differentiated malignant digestive neuroendocrine tumors, Ki67 proliferation index of up to 5%, stable disease before treatment, and low-to-moderate hepatic tumor involvement (≤ 25%) are associated with tumor control during lanreotide treatment. These data if confirmed in prospective trials will help in rationalizing the use of somatostatin analogs with antiproliferative intent.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Cell Proliferation / drug effects
  • Digestive System Neoplasms / drug therapy*
  • Digestive System Neoplasms / pathology
  • Female
  • Humans
  • Ki-67 Antigen / analysis
  • Male
  • Middle Aged
  • Neuroendocrine Tumors / drug therapy*
  • Neuroendocrine Tumors / pathology
  • Neuroendocrine Tumors / secondary
  • Peptides, Cyclic / pharmacology
  • Peptides, Cyclic / therapeutic use*
  • Prognosis
  • Retrospective Studies
  • Somatostatin / analogs & derivatives*
  • Somatostatin / pharmacology
  • Somatostatin / therapeutic use
  • Survival Analysis
  • Treatment Outcome
  • Tumor Burden
  • Young Adult

Substances

  • Antineoplastic Agents
  • Ki-67 Antigen
  • Peptides, Cyclic
  • lanreotide
  • Somatostatin