Phase II study of sunitinib in Japanese patients with unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumor

• Published in: Investigational new drugs Vol. 31; no. 5; pp. 1265 - 1274
• Main Authors: Ito, Tetsuhide, Okusaka, Takuji, Nishida, Toshirou, Yamao, Kenji, Igarashi, Hisato, Morizane, Chigusa, Kondo, Shunsuke, Mizuno, Nobumasa, Hara, Kazuo, Sawaki, Akira, Hashigaki, Satoshi, Kimura, Nobuyuki, Murakami, Mami, Ohki, Emiko, Chao, Richard C., Imamura, Masayuki
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2013; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Analysis; Angiogenesis Inhibitors - blood; Angiogenesis Inhibitors - pharmacokinetics; Angiogenesis Inhibitors - therapeutic use; Antineoplastic agents; Asian Americans; Asian Continental Ancestry Group; Biological and medical sciences; Biomarkers, Tumor - blood; Cancer therapies; Chromogranin A - blood; Confidence intervals; Drug dosages; Drug therapy; Female; Gastrins - blood; Gastroenterology. Liver. Pancreas. Abdomen; General aspects; Hospitals; Humans; Indoles - blood; Indoles - pharmacokinetics; Indoles - therapeutic use; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Magnetic resonance imaging; Male; Medical sciences; Medicine; Medicine & Public Health; Metastasis; Middle Aged; Neoplasm Metastasis; Neuroendocrine tumors; Neuroendocrine Tumors - blood; Neuroendocrine Tumors - drug therapy; Neuroendocrine Tumors - pathology; Oncology; Pancreatic cancer; Pancreatic Neoplasms - blood; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - pathology; Pharmaceutical sciences; Pharmacokinetics; Pharmacology. Drug treatments; Pharmacology/Toxicology; Phase II Studies; Pyrroles - blood; Pyrroles - pharmacokinetics; Pyrroles - therapeutic use; Response rates; Studies; Sunitinib; Surgery; Treatment Outcome; Tumors; Vascular endothelial growth factor; White people; Asia; Japan; Efficacy; Sunitinib; Phase II; Pharmacokinetics; Japanese; Pancreatic neuroendocrine tumor; Antineoplastic agent; Toxicity; Metastasis; Phase II trial; Advanced stage; Antiangiogenic agent; Protein-tyrosine kinase; Pancreatic disease; Human; Enzyme; Tyrosine kinase inhibitor; Transferases; Treatment efficiency; Enzyme inhibitor; Malignant tumor; Treatment; Unresectable; Digestive diseases; Multikinase inhibitor; Cancer
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-012-9910-y

Summary Background. Pancreatic neuroendocrine tumors (NETs) are rare but are frequently diagnosed at advanced stages and require systemic therapy. Patients and 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.