title: Phase II study of sunitinib in Japanese patients with unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumor.
abstract: BACKGROUND
  Pancreatic neuroendocrine tumors (NETs) are rare but are frequently diagnosed at advanced stages and require systemic therapy.
  
  
  METHODS
  This multicenter, open-label, phase II study evaluated sunitinib in Japanese patients with well-differentiated pancreatic NET. Patients received sunitinib 37.5 mg/day on a continuous daily dosing (CDD) schedule. The primary endpoint was clinical benefit rate (CBR; percentage of complete responses [CRs] plus partial responses [PRs] plus stable disease [SD] ≥ 24 weeks). Secondary endpoints included objective response rate (ORR), tumor shrinkage, progression-free survival (PFS) probability, safety, pharmacokinetics, and biomarkers.
  
  
  RESULTS
  Twelve patients received treatment. The CBR was 75 % (95 % confidence interval [CI], 43-94) and included 6 patients with a PR and 3 with SD. The ORR was 50 % (95 % CI, 21-79). PFS probability was 91 % (95 % CI, 54-99) at 6 months and 71 % (95 % CI, 34-90) at 12 months. Commonly reported treatment-emergent (all-causality), any-grade adverse events included diarrhea (n=10), hand-foot syndrome and hypertension (both n=8), fatigue and headache (both n=7), and neutropenia (n=6). No deaths on study were reported; one death due to disease progression occurred >28 days after end of treatment. Sunitinib on a CDD schedule resulted in sustained drug concentrations without accumulation across cycles. Tumor responses in all 12 patients did not appear to correlate with decreases in chromogranin A levels.
  
  
  CONCLUSIONS
  Sunitinib 37.5 mg/day on a CDD schedule demonstrated antitumor activity in Japanese patients with unresectable, well-differentiated pancreatic NET. Commonly reported adverse events were consistent with the known safety profile of sunitinib.
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, Japan, itopapa@intmed3.med.kyushu-u.ac.jp.
authors.forename: Tetsuhide
authors.initials: T
authors.lastname: Ito
authors.forename: Takuji
authors.initials: T
authors.lastname: Okusaka
authors.forename: Toshirou
authors.initials: T
authors.lastname: Nishida
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamao
authors.forename: Hisato
authors.initials: H
authors.lastname: Igarashi
authors.forename: Chigusa
authors.initials: C
authors.lastname: Morizane
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kondo
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Mizuno
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hara
authors.forename: Akira
authors.initials: A
authors.lastname: Sawaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hashigaki
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kimura
authors.forename: Mami
authors.initials: M
authors.lastname: Murakami
authors.forename: Emiko
authors.initials: E
authors.lastname: Ohki
authors.forename: Richard C
authors.initials: RC
authors.lastname: Chao
authors.forename: Masayuki
authors.initials: M
authors.lastname: Imamura
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D044466:Asian People; D014408:Biomarkers, Tumor / Q000097:blood; D053379:Chromogranin A / Q000097:blood; D005260:Female; D005755:Gastrins / Q000097:blood; D006801:Humans; D007211:Indoles / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018358:Neuroendocrine Tumors / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D011758:Pyrroles / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D053379:Chromogranin A; D005755:Gastrins; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib