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

Tetsuhide Ito, 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

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Abstract

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.

Original languageEnglish
Pages (from-to)1265-1274
Number of pages10
JournalInvestigational New Drugs
Volume31
Issue number5
DOIs
Publication statusPublished - Oct 1 2013

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Neuroendocrine Tumors
Confidence Intervals
Appointments and Schedules
Disease-Free Survival
Hand-Foot Syndrome
Safety
Chromogranin A
Therapeutics
sunitinib
Neutropenia
Causality
Fatigue
Headache
Disease Progression
Diarrhea
Neoplasms
Pharmacokinetics
Biomarkers
Hypertension
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

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

In: Investigational New Drugs, Vol. 31, No. 5, 01.10.2013, p. 1265-1274.

Research output: Contribution to journalArticle

Ito, T, Okusaka, T, Nishida, T, Yamao, K, Igarashi, H, Morizane, C, Kondo, S, Mizuno, N, Hara, K, Sawaki, A, Hashigaki, S, Kimura, N, Murakami, M, Ohki, E, Chao, RC & Imamura, M 2013, 'Phase II study of sunitinib in Japanese patients with unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumor', Investigational New Drugs, vol. 31, no. 5, pp. 1265-1274. https://doi.org/10.1007/s10637-012-9910-y
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. / Phase II study of sunitinib in Japanese patients with unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumor. In: Investigational New Drugs. 2013 ; Vol. 31, No. 5. pp. 1265-1274.
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abstract = "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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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

PY - 2013/10/1

Y1 - 2013/10/1

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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