Capecitabine and temozolomide combination for treatment of high-grade, well-differentiated neuroendocrine tumour and poorly-differentiated neuroendocrine carcinoma — retrospective analysis

Abstract

Introduction: Many retrospective studies have confirmed that capecitabine combined with temozolomide is effective in neuroendocrine neoplasms. Most of the studies focused on grade 1 and grade 2 neuroendocrine tumours, mainly of pancreatic origin. There are limited data regarding the efficacy capecitabine with temozolomide in grade 3 neuroendocrine tumours. The new World Health Organisation 2017 classification distinguished well-differentiated grade 3 neuroendocrine tumours from poorly differentiated grade 3 neuroendocrine carcinomas. Treatment options for grade 3 neuroendocrine neoplasms are limited, and the overall prognosis is better in the subgroup of patients with grade 3 neuroendocrine tumours. Material and methods: It was a retrospective study in the population of patients with diagnosed grade 3 neuroendocrine neoplasms of different origin treated with capecitabine and temozolomide. Data on clinical and demographic characteristics of the population were collected from four Polish clinical centres. This study aimed to evaluate response and survival parameters and compare outcomes of treatment of neuroendocrine tumours and carcinomas. Results: The study included 32 patients with grade 3 neuroendocrine tumours treated with capecitabine and temozolomide. The disease control rate was twice as high in the group of patient with neuroendocrine tumours in comparison to carcinomas (70 vs. 30%). The progression-free survival for patients with neuroendocrine tumours was 15.3 months (95% CI: 3.9-30.4), and for patients with neuroendocrine carcinomas it was 3.3 months (95% CI: 2.5-7.1). Median overall survival was 22 months (95% CI: 11.8-22.0) and 4.6 months (95% CI: 2.2-5.9) for patients with tumours and carcinomas, respectively. The treatment regimen was generally well tolerated. Conclusions: The combination of capecitabine and temozolomide is an effective treatment for patients with grade 3 neuroendocrine tumours with Ki-67 index ranging between 20 and 54%. The treatment did not overcome the aggressive character of neuroendocrine carcinomas and resulted in low response and survival outcomes in comparison to those achieved in tumour therapy. (Endokrynol Pol 2019; 70 (4): 313-317)

Systemic Treatment of Gastroenteropancreatic Neuroendocrine Carcinoma

“…Only 16 were evaluable for radiological response and DCR was 38%, while no PR or CR were observed. Efficacy of temozolomide plus capecitabine was further assessed[52] in patients with GEP-NET G3 (n=20) and GEP-NEC G3 (n=12). DCR was 70% in the NET group and 30% in NEC group.…”

PRRT in high-grade gastroenteropancreatic neuroendocrine neoplasms (WHO G3)

“…A NET G2-like medical treatment strategy as tested in recent small retrospective studies may be more appropriate for patients with NET G3. Temozolomide/ capecitabine in patients with NET G3 tumors resulted in a disease control rate of 70%, PFS 15 months and OS 22 months (Rogowski et al 2019). Everolimus in patients with pancreatic NET G3 with a Ki-67 ≤55% resulted in a PFS of 6 months and OS of 28 months (Panzuto et al 2017).…”

Malignant Gastrointestinal Neuroectodermal Tumor (GNET) with Prolonged Disease-Free Survival after Platinum-Based Chemotherapy

“…The patient was initially treated with systemic chemotherapy utilizing capecitabine 1500 mg/m 2 po BID D1-14 and temozolomide 150 mg/m 2 D10-14 every 28 days [ 2 ]. Imaging studies after 4 cycles of chemotherapy showed interval progression of the disease with development of numerous liver lesions and increased size of peritoneal masses.…”

“…It was previously known as clear cell sarcoma-like tumor of the GI tract (CCSLTGT) [ 1 ]. In the recent years, it has been recognized as a separate entity with specific histologic, immunohistochemistry, and molecular features [ 2 ]. GNET carries a poor prognosis, and systemic therapeutic options are very limited with lack of guidelines or management recommendation.…”