title: Targeted therapies in neuroendocrine tumors (NET): clinical trial challenges and lessons learned.
abstract: In the past 3 years, we have witnessed the completion of four randomized phase III studies in neuroendocrine tumors and the approval of two new drugs, everolimus and sunitinib, for the treatment of patients with well-differentiated pancreatic neuroendocrine tumors. These studies demonstrate a shift from case series and single-arm studies toward prospective, randomized controlled clinical trials and evidence-based therapy in the neuroendocrine tumor field. However, the clinical development of these agents also highlights the potential challenges awaiting other new drugs in this area. Herein, we discuss the strengths and weaknesses of the most recent phase II and phase III neuroendocrine tumor studies and discuss how limitations inherent in current trial design can lead to potential pitfalls. We also discuss how trial design can be improved, with the hope of increasing the number of drugs successfully developed to treat patients with neuroendocrine tumors.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. jyao@mdanderson.org
authors.forename: James C
authors.initials: JC
authors.lastname: Yao
authors.forename: Diane Reidy
authors.initials: DR
authors.lastname: Lagunes
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Kulke
mesh_terms: D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D000068338:Everolimus; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D058990:Molecular Targeted Therapy; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011758:Pyrroles / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077210:Sunitinib
chemical_list: D007211:Indoles; D011758:Pyrroles; D000068338:Everolimus; D000077210:Sunitinib; D020123:Sirolimus
keywords: Everolimus; Neuroendocrine tumors; Octreotide; Sunitinib; Trial design