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

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.