Chemotherapy in Neuroendocrine Tumors

SIMPLE SUMMARY: Cytotoxic chemotherapy is a standard therapy for patients with poorly differentiated neuroendocrine carcinomas, however, its role in patients with well differentiated neuroendocrine tumors is less defined. In this review, we describe the data supporting many of the chemotherapy regimens which have been tested in patients with well differentiated neuroendocrine tumors, specifically focusing on the impact of tumor features (e.g., primary tumor origin, grade and DNA damage repair defects) on chemosensitivity, and discuss future directions for chemotherapy as a combinatorial treatment modality for patients with this disease. ABSTRACT: The role for cytotoxic chemotherapy in patients with well-differentiated neuroendocrine tumors (NETs) remains debated. Compared to patients with poorly differentiated neuroendocrine carcinomas (NECs) where chemotherapy is utilized ubiquitously, chemotherapy may play a more select role in patients with certain types of NETs (e.g., pancreatic tumors, higher grade tumors, and tumors possessing DNA damage repair defects). The primary types of chemotherapy that have been tested in patients with NETs include alkylating agent- and platinum agent-based combinations. Across regimens, chemotherapy appears to elicit greater antitumor activity in patients with pancreatic or grade 3 NETs. The role for chemotherapy in lower grade extra-pancreatic NETs remains undefined. Furthermore, while chemotherapy has demonstrated clinically meaningful benefit for patients in the systemic setting, its role in the adjuvant or neoadjuvant setting is as-of-yet undetermined. Finally, efforts to combine chemotherapy with targeted therapy and peptide receptor radionuclide therapy are ongoing, in hopes of improving the cytoreductive treatment options for patients with NETs.