Novel fluoropyrimidine-based chemotherapy for advanced well-differentiated neuroendocrine tumors: a clinical update

ABSTRACT

Introduction: Patients with advanced well-differentiated neuroendocrine tumors (NETs) who have bulky and/or symptomatic and/or rapidly progressive disease require chemotherapy treatment.

Areas covered: This review summarizes the accumulating evidence for treatment with fluorouracil-based chemotherapy in well-differentiated NETs. The main clinical studies, toxicity and predictors of fluorouracil- based chemotherapy regimens in well-differentiated NETs are discussed, along with the current issues, future research directions and therapeutic prospects.

Expert opinion: Somatostatin analogs may control symptoms of hormone excess and tumor growth in patients with well-differentiated metastatic NETs, and biological therapies may improve progression-free survival for these patients. However, chemotherapy leads to higher objective response rates and symptom control by reducing tumor bulk. The low response rate and significant toxicities of conventional chemotherapy regimens limit their widespread use. Fortunately, some novel fluoropyrimidine-based treatment including fluorouracil, capecitabine, or S-1 based chemotherapy with or without antiangiogenic agents have been investigated in recent years. These treatments showed significant efficacy and less toxicity in pancreatic and non-pancreatic metastatic well-differentiated NETs. Additionally, non-pancreatic well-differentiated NETs have also achieved similar tumor response or survival comparable to pancreatic NETs. Moreover, some predictors of response to these treatment regimens have been evaluated.

KEYWORDS:

• Chemotherapy
• fluoropyrimidine
• well-differentiated
• neuroendocrine tumours
• predictor

Article highlights

• Patients with advanced well-differentiated NETs who have high tumor burden and/or symptomatic and/or rapidly progressive disease need be treated with chemotherapy.

• Recently some novel fluoropyrimidine-based chemotherapy regimens including CAPTEM, CapeOx and FOLFOX, STEM, CapStrep and CapStrepCis and Capecitabine monotherapy shown had better curative effect and acceptable toxicity in advanced well-differentiated NETs.

• These novel fluoropyrimidine-based chemotherapy regimens appeared to be active in both pancreatic endocrine tumors and nonpancreatic NETs.

• Some predictors of response to novel fluoropyrimidine-based treatment for advanced well-differentiated NETs have been explored.

• Prospective studies are needed to adequately investigate the role of novel fluoropyrimidine-based chemotherapy regimens in well-differentiated NETs.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This work was supported by grants from the Thousand Talents of Program of High-end Innovation of Qinghai Province in China (awarded to J Zhao and G Shen).