Phase II study of sunitinib in Japanese patients w

Authors: 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

Publish Date: 2013/10/01

Volume: 31, Issue: 5, Pages: 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 openlabel phase II study evaluated sunitinib in Japanese patients with welldifferentiated pancreatic NET Patients received sunitinib 375 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 progressionfree 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 treatmentemergent allcausality anygrade 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 375 mg/day on a CDD schedule demonstrated antitumor activity in Japanese patients with unresectable welldifferentiated pancreatic NET Commonly reported adverse events were consistent with the known safety profile of sunitinibWe 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 IncRichard 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

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