Safety and Efficacy of the S-1/Temozolomide Regimen in Patients with Metastatic Neuroendocrine Tumors

Abstract

Purpose: Both capecitabine alone and capecitabine in combination with temozolomide have activities against neuroendocrine tumors (NETs). However, the role of S-1 in NETs is still unknown. We performed a study to evaluate the safety and efficacy of the S-1/temozolomide (STEM) regimen in patients with locally advanced or metastatic NETs. Methods: A retrospective review was conducted in 20 patients with locally advanced or metastatic NETs treated with the STEM regimen. Of the patients, 15 (75.00%) had failed 1 or more lines of treatment with somatostatin analogues, sunitinib, everolimus, anlotinib, or other chemotherapy regimens. The patients received S-1 at 40 mg/m² orally twice daily on days 1-14 and temozolomide 200 mg orally once daily on days 10-14 of a 21-day cycle. The patients were followed up for evidence of object response, toxicity, and progression-free survival. Results: Response to treatment was assessed using RECIST 1.1. Eight patients (40.00%) achieved a partial response (PR), and another 8 (40.00%) had stable disease (SD). The clinical benefit rate (PR and SD) was 80.00%. The median progression-free survival was not achieved. Only 1 patient (5.00%) had grade 3 adverse events. Among the patients with NETs of different origins, 4 (40.00%) and 5 (50.00%) with pancreatic NETs attained PR and SD, respectively. Four (40.00%) and 3 patients (30.00%) with nonpancreatic NETs attained PR and SD, respectively. Conclusions: The STEM regimen is exceptionally highly active and well tolerated in patients with locally advanced or metastatic NETs. Even in patients who showed disease progression with previous therapies, it is still highly active. In this 20-patient study, the regimen appeared to be similarly active in pancreatic endocrine tumors and nonpancreatic NETs.

Intratumoral injection of anlotinib hydrogel enhances antitumor effects and reduces toxicity in mouse model of lung cancer

“…It was approved as an optional third-line treatment for refractory advanced non-small cell lung cancer (Han et al., 2018a,b; Chen, 2019 ; Zhou et al., 2019 ). Like other analogous agents, the most common adverse effects of AL are hypertension, triglyceride elevation, elevated thyroid-stimulating hormone (TSH) (Sun et al., 2016 ; Si et al., 2018 ; Zhao et al., 2018 ). The pattern of systemic administration determines the increase in local blood concentrations along with increased systemic cardiovascular toxicity.…”

S-1/temozolomide versus S-1/temozolomide plus thalidomide in advanced pancreatic and non-pancreatic neuroendocrine tumours (STEM): A randomised, open-label, multicentre phase 2 trial

“… 15 We have previously reported that S-1 plus temozolomide has strong anti-tumour efficacy and is well tolerated in patients with locally advanced or metastatic NETS. 16 Thalidomide, an angiogenesis inhibitor that can suppress cell proliferation and tumour angiogenesis, has also shown an anti-tumour effect against NETS. 17 A phase II study demonstrated that temozolomide combined with thalidomide resulted in an overall ORR of 25%, and a 2-year survival rate of 70% in patients with metastatic NETS.…”