New drugs in neuroendocrine tumors: rising of new therapeutic philosophies?
OBJECTIVE
There has been a major progress in the understanding of tumor biology during the past decades and, as a consequence, new potential targets for medical treatment of cancer have been identified. Some of the new so-called targeted therapies may prove to be of value also in neuroendocrine tumors (NETs). This review focuses on recent progress in the treatment of NETs, discussing new agents and also optimization/improvement of currently available therapies.


RESULTS
New molecular-targeted therapies, exploiting some of the well known biological properties of NETs, such as presence of somatostatin, peptide and tyrosine kinase receptors and high vascularity, are currently being evaluated in clinical trials. Recent phase II and III data indicate that the multitarget tyrosine kinase inhibitor sunitinib has antiproliferative effects in NETs. Similarly, the mammalian target of rapamycin inhibitor everolimus has demonstrated antitumor activity in both carcinoids and pancreatic endocrine tumors. In addition, two oral chemotherapeutic agents, temozolomide and capecitabine, show promising effects and may replace streptozotocin-based regimens. The use of angiogenesis inhibitors has its rationale and bevacizumab has been tested in combination with other drugs. Radiolabeled somatostatin analogues are established as a well tolerated, effective treatment but timing is still unclear and long-term side effects need to be assessed.


CONCLUSIONS
Recent phase II studies have provided very promising new treatment options for NET patients. Phase III trials are needed to confirm the results and combinations of different treatment modalities are needed to make optimal use of the new modalities. Ideally, predictors of response should be developed and the new definitions of response necessitates careful monitoring with biomarkers and imaging procedures including functional imaging. Whether the new therapies prolong survival of the patients should also be established.
Eriksson
Barbro
B
Department of Endocrine Oncology, Institution for Medical Sciences, Uppsala University Hospital, Uppsala, Sweden. barbro.eriksson@medsci.uu.se
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000069287:Capecitabine; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004358:Drug Therapy / Q000379:methods* / Q000639:trends; D000068338:Everolimus; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D018358:Neuroendocrine Tumors / Q000188:drug therapy*; D015282:Octreotide / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077210:Sunitinib; D000077204:Temozolomide; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D003841:Deoxycytidine; D000069287:Capecitabine; D003606:Dacarbazine; D000068338:Everolimus; D015282:Octreotide; D005472:Fluorouracil; D000077210:Sunitinib; D020123:Sirolimus; D000077204:Temozolomide