Efficacy of Capecitabine and Temozolomide in Small Bowel (Midgut) Neuroendocrine Tumors.

Taymeyah Al-Toubah,Brian Morse,Jonathan Strosberg

doi:10.3390/curroncol29020046

Taymeyah Al-Toubah, Brian Morse + Show 1 more

Open Access

https://doi.org/10.3390/curroncol29020046

Copy DOI

Journal: Current Oncology	Publication Date: Jan 26, 2022
Citations: 10	License type: CC BY 4.0

Affiliation: Moffitt Cancer Center

Abstract

Simple SummaryThe capecitabine/temozolomide (CAPTEM) regimen has proven activity in pancreatic neuroendocrine tumors (NETs); however, data are limited in NETs of the small bowel. To observe whether this regimen has activity in this patient population, we conducted a retrospective study of all patients with small bowel NETs treated with this regimen at our institution. We found that response rates were poor among patients with low-intermediate grade tumors but higher among patients with high-grade disease. Our findings suggest that the CAPTEM regimen should be reserved for patients with higher-grade small bowel NETs.The capecitabine/temozolomide regimen has significant activity in pancreatic NETs; however, data are limited in NETs of the small bowel (midgut). A retrospective study of all patients with metastatic midgut NETs seen at Moffitt Cancer Center between January 2008 and June 2019 treated with CAPTEM was conducted. 32 patients with proven or suspected well-differentiated primary small bowel NETs (excluding duodenum) were identified. 6 patients were found to have a radiographic response (19%), 5 of whom had high-grade disease. Only one patient among 23 with low/intermediate-grade disease responded (4%), whereas the response rate for patients with high-grade disease was 56%. Among patients with low/intermediate-grade disease, 44% discontinued due to poor tolerability. The CAPTEM regimen appears to have an activity in patients with high-grade small bowel NETs and is largely inactive in patients with low/intermediate-grade tumors.

Highlights

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are clinically and biologically heterogeneous neoplasms [1]
The randomized phase II ECOG 2211 trial demonstrated a significant improvement in progression-free survival (PFS) and overall survival (OS) with the capecitabine and temozolomide (CAPTEM) combination compared with temozolomide monotherapy [14]
We reviewed our experience with CAPTEM in midgut NETs, with a focus on the comparison of high-grade tumors versus low/intermediate-grade disease

Summary

Introduction

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are clinically and biologically heterogeneous neoplasms [1]. The two most common subtypes, midgut and pancreatic NETs, are distinct in their underlying mutational landscape, hormonal secretion profile, and response to various anti-cancer therapies [2,3]. Pancreatic NETs are more distributed between indolent and aggressive and are characterized by higher objective response rates to most therapies, including targeted drugs and peptide receptor radiotherapy (PRRT) [4,5]. One of the most striking differences between pancreatic and midgut NETs is their differential response to cytotoxic therapy, with objective response rates (ORR) of approximately 50% reported in patients with pancreatic NETs treated with alkylating or platinum-based regimens, versus 0–10% among midgut NET patients [6,7,8,9,10]. The most studied cytotoxic regimen in the NET field has consisted of capecitabine and temozolomide (CAPTEM). CAPTEM is recommended by multiple expert consensus guidelines for the treatment of advanced, progressive pancreatic NETs [17,18,19]

Methods

Results

Conclusion