TY - JOUR
T1 - Phase II study of sunitinib in Japanese patients with unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumor
AU - Ito, Tetsuhide
AU - Okusaka, Takuji
AU - Nishida, Toshirou
AU - Yamao, Kenji
AU - Igarashi, Hisato
AU - Morizane, Chigusa
AU - Kondo, Shunsuke
AU - Mizuno, Nobumasa
AU - Hara, Kazuo
AU - Sawaki, Akira
AU - Hashigaki, Satoshi
AU - Kimura, Nobuyuki
AU - Murakami, Mami
AU - Ohki, Emiko
AU - Chao, Richard C.
AU - Imamura, Masayuki
N1 - Funding Information:
Acknowledgments We would like to thank all of the participating patients and their families, as well as the network of investigators, research nurses, study coordinators, and operations staff. We are also grateful to Kyoko Okano and Junichi Tanuma (Pfizer Japan Inc.) for their contributions to study management and to Atsushi Shibata for advice regarding the safety profile of sunitinib. Medical writing support was provided by Molly Heitz at ACUMED® (Tytherington, UK) with funding from Pfizer Inc.
Funding Information:
This study was sponsored by Pfizer Inc.
Funding Information:
Conflict of interest Richard Chao, Satoshi Hashigaki, Nobuyuki Kimura, and Emiko Ohki are employees of Pfizer, and N. Kimura, E. Ohki, and R. Chao hold Pfizer stock. Mami Murakami was previously employed by Pfizer. Tetsuhide Ito, Takuji Okusaka and Kenji Yamao have received research funding from Pfizer. Toshirou Nishida has received research funding from Pfizer and Novartis Pharmaceuticals. Hisato Igarashi, Nobumasa Mizuno, Kazuo Hara, Chigusa Morizane, Shunsuke Kondo, Akira Sawaki, and Masayuki Imamura have no potential conflicts of interest to disclose.
PY - 2013/10
Y1 - 2013/10
N2 - 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.
AB - 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.
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U2 - 10.1007/s10637-012-9910-y
DO - 10.1007/s10637-012-9910-y
M3 - Article
C2 - 23269537
AN - SCOPUS:84884817266
SN - 0167-6997
VL - 31
SP - 1265
EP - 1274
JO - Investigational New Drugs
JF - Investigational New Drugs
IS - 5
ER -
