Capecitabine and temozolomide combination for treatment of high-grade well-differentiated neuroendocrine tumour and poorly-differentiated neuroendocrine carcinoma. Retrospective analysis.

INTRODUCTION: Many retrospective studies confirmed that capecitabine combined with temozolomide is effective in treatment of neuroendocrine neoplasm. Most of studies focused on grade 1 and grade 2 neuroendocrine tumours, mainly of pancreas origin. There are limited data regarding efficacy capecitabine with temozolomide in grade 3 neuroendocrine tumours. The new World Health Organization 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 overall prognosis is better in the subgroup of patients with grade 3 neuroendocrine tumours.

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 was 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. Disease control rate was twice higher 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 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: Capecitabine and temozolomide combination is effective treatment for patients with grade 3 neuroendocrine tumours with Ki-67 index ranging between 20 and 54%. The treatment did not overcome aggressive character of neuroendocrine carcinomas and resulted is low response and survival outcomes in comparison to those achieved in tumours therapy.