A phase I dose-escalation study of ZD6474 in Japanese patients with solid, malignant tumors

Tomohide Tamura, Hironobu Minami, Yasuhide Yamada, Noboru Yamamoto, Tatsu Shimoyama, Haruyasu Murakami, Atsushi Horiike, Yasuhito Fujisaka, Tetsu Shinkai, Makoto Tahara, Kenji Kawada, Hiromichi Ebi, Yasutsuna Sasaki, Haiyi Jiang, Nagahiro Saijo

研究成果: ジャーナルへの寄稿学術論文査読

141 被引用数 (Scopus)

抄録

INTRODUCTION: ZD6474 (vandetanib) is an orally available inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor, and RET receptor tyrosine kinase activity. This study assessed the safety and tolerability of escalating doses of ZD6474 in Japanese patients with solid, malignant tumors. METHODS: Adult patients with solid tumors refractory to standard therapy received a once-daily oral dose of ZD6474 (100-400 mg) in 28-day cycles, until disease progression or unacceptable toxicity was observed. RESULTS: Eighteen patients were treated at doses of 100 mg (n = 3), 200 mg (n = 6), 300 mg (n = 6), and 400 mg (n = 3). Dose-limiting toxicities at the completion of cycle 2 were hypertension (n = 3), diarrhea (n = 1), headache (n = 1), toxic skin eruption (n = 1), and alanine aminotransferase increase (n = 1). A dose of 400 mg/day was considered to exceed the maximum tolerated dose (MTD). Toxicities were manageable with dose interruption and/or reduction. Objective tumor response was observed in four of nine patients with non-small cell lung cancer (NSCLC) at doses of either 200 or 300 mg. Terminal half-life was about 90-115 hours. Plasma trough concentrations achieved steady-state conditions after approximately 1 month of daily dosing. CONCLUSIONS: It was concluded that a dose of 400 mg/day was considered to exceed the MTD, and doses for phase II study were thought to be not more than 300 mg/day. The objective response observed in some NSCLC patients is encouraging for further studies in this tumor type.

本文言語英語
ページ(範囲)1002-1009
ページ数8
ジャーナルJournal of Thoracic Oncology
1
9
DOI
出版ステータス出版済み - 11-2006
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 呼吸器内科

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