title: A phase II study of axitinib in advanced neuroendocrine tumors.
abstract: Neuroendocrine tumors (NETs) are highly vascular neoplasms overexpressing vascular endothelial growth factor (VEGF) as well as VEGF receptors (VEGFR). Axitinib is a potent, selective inhibitor of VEGFR-1, -2 and -3, currently approved for the treatment of advanced renal cell carcinoma. We performed an open-label, two-stage design, phase II trial of axitinib 5mg twice daily in patients with progressive unresectable/metastatic low-to-intermediate grade carcinoid tumors. The primary end points were progression-free survival (PFS) and 12-month PFS rate. The secondary end points included time to treatment failure (TTF), overall survival (OS), overall radiographic response rate (ORR), biochemical response rate and safety. A total of 30 patients were enrolled and assessable for toxicity; 22 patients were assessable for response. After a median follow-up of 29months, we observed a median PFS of 26.7months (95% CI, 11.4-35.1), with a 12-month PFS rate of 74.5% (±10.2). The median OS was 45.3 months (95% CI, 24.4-45.3), and the median TTF was 9.6months (95% CI, 5.5-12). The best radiographic response was partial response (PR) in 1/30 (3%) and stable disease (SD) in 21/30 patients (70%); 8/30 patients (27%) were unevaluable due to early withdrawal due to toxicity. Hypertension was the most common toxicity that developed in 27 patients (90%). Grade 3/4 hypertension was recorded in 19 patients (63%), leading to treatment discontinuation in six patients (20%). Although axitinib appears to have an inhibitory effect on tumor growth in patients with advanced, progressive carcinoid tumors, the high rate of grade 3/4 hypertension may represent a potential impediment to its use in unselected patients.
authors.affiliation: Department of Gastrointestinal OncologyH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA jonathan.strosberg@moffitt.org.
authors.forename: J R
authors.initials: JR
authors.lastname: Strosberg
authors.affiliation: Department of Gastrointestinal OncologyH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: M
authors.initials: M
authors.lastname: Cives
authors.affiliation: Department of Medicine and The UCSF Helen Diller Family Comprehensive Cancer CenterUniversity of California, San Francisco, California, USA.
authors.forename: J
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Department of Medicine and The UCSF Helen Diller Family Comprehensive Cancer CenterUniversity of California, San Francisco, California, USA.
authors.forename: T
authors.initials: T
authors.lastname: Weber
authors.affiliation: Department of Medicine and The UCSF Helen Diller Family Comprehensive Cancer CenterUniversity of California, San Francisco, California, USA.
authors.forename: M
authors.initials: M
authors.lastname: Nickerson
authors.affiliation: Department of Medicine and The UCSF Helen Diller Family Comprehensive Cancer CenterUniversity of California, San Francisco, California, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Atreya
authors.affiliation: Department of Medicine and The UCSF Helen Diller Family Comprehensive Cancer CenterUniversity of California, San Francisco, California, USA.
authors.forename: A
authors.initials: A
authors.lastname: Venook
authors.affiliation: Department of Medicine and The UCSF Helen Diller Family Comprehensive Cancer CenterUniversity of California, San Francisco, California, USA.
authors.forename: R K
authors.initials: RK
authors.lastname: Kelley
authors.affiliation: Department of Gastrointestinal OncologyH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: T
authors.initials: T
authors.lastname: Valone
authors.affiliation: Department of Gastrointestinal OncologyH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: B
authors.initials: B
authors.lastname: Morse
authors.affiliation: Department of Gastrointestinal OncologyH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: D
authors.initials: D
authors.lastname: Coppola
authors.affiliation: Department of Medicine and The UCSF Helen Diller Family Comprehensive Cancer CenterUniversity of California, San Francisco, California, USA.
authors.forename: E K
authors.initials: EK
authors.lastname: Bergsland
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077784:Axitinib; D003110:Colonic Neoplasms / Q000188:drug therapy; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D007191:Indazoles / Q000009:adverse effects / Q000627:therapeutic use*; D007414:Intestinal Neoplasms / Q000188:drug therapy; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012004:Rectal Neoplasms / Q000188:drug therapy; D013953:Thymus Neoplasms / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D000077784:Axitinib
keywords: VEGF; VEGFR; antiangiogenesis; carcinoid tumor; tyrosine kinase inhibitor