Pancreatic NETs: where do we stand now?

• Published in: Cancer and metastasis reviews Vol. 33; no. 1; pp. 361 - 366
• Main Authors: Faivre, S., Castellano, D., Strosberg, J., González, E., Salazar, R.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.03.2014; Springer; Springer Nature B.V
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Chemotherapy; Disease-Free Survival; DNA Modification Methylases - metabolism; DNA Repair Enzymes - metabolism; Everolimus; Humans; Indoles - therapeutic use; Neuroendocrine Tumors - diagnosis; Neuroendocrine Tumors - drug therapy; Neuroendocrine Tumors - enzymology; Oncology; Pancreatic Neoplasms - diagnosis; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - enzymology; Pyrroles - therapeutic use; Sirolimus - analogs & derivatives; Sirolimus - therapeutic use; Treatment Outcome; Tumor Suppressor Proteins - metabolism; mTOR inhibitors; Chemotherapy; Sunitinib; Targeted therapy; Antiangiogenics; Everolimus
• ISSN: 0167-7659; 1573-7233
• DOI: 10.1007/s10555-013-9466-0

The systemic management of patients with pancreatic neuroendocrine tumors includes chemotherapy and targeted agents such as everolimus and sunitinib. Which treatment to favor in a particular patient is not known. The most commonly used chemotherapy agents are streptozocin and temozolamide, often prescribed in combination with fluoropyrimidines. A potential biomarker for selection of temozolomide-based chemotherapy is O-6-methylguanine-DNA-methyltrasferase expression. Chemotherapy yields higher response rates and may be preferable in patients with higher-grade tumors and those who are symptomatic. The mammalian target of rapamycin inhibitor everolimus has shown improvement in progression-free survival (PFS) in a robust, well-conducted phase III study. Everolimus, however, can induce limiting toxicities that may result in treatment discontinuation and does not improve survival. However, the objective response rate is very low. Sunitinib, likewise, increases PFS but the data comes from a smaller trial which was terminated early. Sunitinib displays a different toxicity profile and is associated with a trend towards improved overall survival. It is clear that biomarkers to properly select the most effective agents in an individual patient are needed.