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Investigational New Drugs

, Volume 31, Issue 5, pp 1265–1274 | Cite as

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

  • Tetsuhide ItoEmail author
  • Takuji Okusaka
  • Toshirou Nishida
  • Kenji Yamao
  • Hisato Igarashi
  • Chigusa Morizane
  • Shunsuke Kondo
  • Nobumasa Mizuno
  • Kazuo Hara
  • Akira Sawaki
  • Satoshi Hashigaki
  • Nobuyuki Kimura
  • Mami Murakami
  • Emiko Ohki
  • Richard C. Chao
  • Masayuki Imamura
PHASE II STUDIES

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.

Keywords

Efficacy Japanese Pancreatic neuroendocrine tumor Pharmacokinetics Phase II Sunitinib 

Notes

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

This study was sponsored by Pfizer Inc.

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.

Supplementary material

10637_2012_9910_MOESM1_ESM.doc (108 kb)
Table S1 (DOC 107 kb)

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Copyright information

© The Author(s) 2012

Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

Authors and Affiliations

  • Tetsuhide Ito
    • 1
    Email author
  • Takuji Okusaka
    • 2
  • Toshirou Nishida
    • 3
  • Kenji Yamao
    • 4
  • Hisato Igarashi
    • 1
  • Chigusa Morizane
    • 2
  • Shunsuke Kondo
    • 2
  • Nobumasa Mizuno
    • 4
  • Kazuo Hara
    • 4
  • Akira Sawaki
    • 4
    • 5
  • Satoshi Hashigaki
    • 6
  • Nobuyuki Kimura
    • 6
  • Mami Murakami
    • 6
    • 9
  • Emiko Ohki
    • 6
  • Richard C. Chao
    • 7
  • Masayuki Imamura
    • 8
  1. 1.Department of Medicine and Bioregulatory Science, Graduate School of Medical ScienceKyushu UniversityFukuokaJapan
  2. 2.Hepatobiliary and Pancreatic Oncology DivisionNational Cancer Center HospitalTokyoJapan
  3. 3.Department of SurgeryOsaka Police HospitalOsakaJapan
  4. 4.Department of GastroenterologyAichi Cancer Center HospitalNagoyaJapan
  5. 5.Nagoya Daini Red Cross HospitalNagoyaJapan
  6. 6.Pfizer Japan Inc.TokyoJapan
  7. 7.Pfizer OncologyLa JollaUSA
  8. 8.Kansai Electric Power Company HospitalOsakaJapan
  9. 9.Drug Delivery and Formulation Group, Medicinal Chemistry PlatformOntario Institute for Cancer ResearchTorontoCanada

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