Irinotecan plus cisplatin followed by octreotide long-acting release maintenance treatment in advanced gastroenteropancreatic neuroendocrine carcinoma: IPO-NEC study

Oncotarget. 2017 Apr 11;8(15):25669-25678. doi: 10.18632/oncotarget.12900.

Abstract

There have been very few prospective studies of first-line chemotherapy on advanced gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC). This phase II study assessed the activity and safety of irinotecan plus cisplatin (IP) followed by octreotide long-acting release (LAR) maintenance treatment in advanced GEP-NEC. Forty patients were treated and eighteen patients (45.0%) had a partial response. The median progression-free survival (PFS) and overall survival (OS) were 5.7 months and 12.9 months, respectively. Because GEP-NECs are heterogeneous, a subgroup analysis was conducted by dividing all patients into a high proliferation neuroendocrine tumor (NET) group (well differentiated neuroendocrine neoplasms with a Ki-67 level between 20-60%) or a poorly differentiated NEC (PDNEC) group. Compared with the PDNEC group, the patients in high proliferation NET group had a lower response rate (0% versus 51.4%) but longer PFS (8.9 versus 5.7 months) and received more octreotide LAR treatment (median cycles, 7 versus 3). The most common toxicities included grade 3/4 leukopenia/neutropenia (60%), nausea/vomiting (17.5%) and diarrhea (12.5%). Therefore, IP is an active regimen in patients with advanced GEP-PDNEC and should probably not be given to patients with advanced high proliferative NET. The benefit of octreotide LAR maintenance therapy on high proliferation NETs requires further study.

Keywords: cisplatin; gastroenteropancreatic neuroendocrine carcinomas; heterogeneous; irinotecan; octreotide long-acting release.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Cisplatin / administration & dosage
  • Female
  • Humans
  • Induction Chemotherapy
  • Intestinal Neoplasms / diagnosis
  • Intestinal Neoplasms / drug therapy*
  • Intestinal Neoplasms / mortality
  • Irinotecan
  • Maintenance Chemotherapy
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neuroendocrine Tumors / diagnosis
  • Neuroendocrine Tumors / drug therapy*
  • Neuroendocrine Tumors / mortality
  • Octreotide / administration & dosage
  • Octreotide / adverse effects
  • Octreotide / therapeutic use*
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / mortality
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / mortality
  • Survival Rate
  • Treatment Outcome

Substances

  • Biomarkers
  • Irinotecan
  • Cisplatin
  • Octreotide
  • Camptothecin

Supplementary concepts

  • Gastro-enteropancreatic neuroendocrine tumor