Pancreatic NETs: where do we stand now?
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.
Department Medical Oncology, Beaujon University Hospital, Clichy, France, sandrine.faivre@bjn.aphp.fr.
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Faivre
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Castellano
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Strosberg
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González
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Salazar
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D015254:DNA Modification Methylases / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000378:metabolism; D018572:Disease-Free Survival; D000068338:Everolimus; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D018358:Neuroendocrine Tumors / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D011758:Pyrroles / Q000627:therapeutic use*; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077210:Sunitinib; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D014408:Biomarkers, Tumor; D007211:Indoles; D011758:Pyrroles; D025521:Tumor Suppressor Proteins; D000068338:Everolimus; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077210:Sunitinib; D020123:Sirolimus