Phase 1 study of pazopanib alone or combined with lapatinib in Japanese patients with solid tumors

Megumi Inada-Inoue, Yuichi Ando, Kenji Kawada, Ayako Mitsuma, Masataka Sawaki, Taro Yokoyama, Yu Sunakawa, Hiroo Ishida, Kazuhiro Araki, Keishi Yamashita, Keiko Mizuno, Fumio Nagashima, Akiko Takekura, Kazuo Nagamatsu, Yasutsuna Sasaki

研究成果: ジャーナルへの寄稿学術論文査読

20 被引用数 (Scopus)

抄録

Purpose: A phase 1 study of pazopanib alone or in combination with lapatinib was conducted to assess the safety, tolerability, and pharmacokinetics of these oral tyrosine kinase inhibitors in Japanese patients with solid tumors. Methods: In part A (monotherapy), 7 patients initially received pazopanib 800 mg/day, the recommended dose for non-Japanese patients. Then, 3 patients received pazopanib 400 mg/day on day 1 followed by 800 mg/day from day 2 onward. Three other patients received pazopanib 1,000 mg/day. In part B (combination therapy), 17 patients received pazopanib plus lapatinib (pazopanib/lapatinib) at once-daily doses of 400/1,000 mg (4 patients), 800/1,000 mg (3 patients), 400/1,500 mg (3 patients), and then 600/1,250 mg (7 patients). Results: There was no dose-limiting toxicity during the study. In part A, most drug-related adverse events were grade 2 or lower, including neutropenia/neutrophil count decreased, thrombocytopenia/platelet count decreased, diarrhea, hypertension, aspartate aminotransferase increased, and lipase increased. In part B, rash, decreased appetite, and serum thyroid-stimulating hormone increased also occurred. In all dose groups, the plasma concentrations after multiple doses of pazopanib exceeded the target trough concentration for inhibition of vascular endothelial growth factor receptor-2 activity (20 μg/mL). Conclusions: The pharmacokinetic profiles of pazopanib and lapatinib in Japanese patients were not apparently different from those reported in non-Japanese patients. There were no consistent trends in pharmacokinetic drug interactions between pazopanib and lapatinib. Pazopanib monotherapy at 800 and 1,000 mg once daily and pazopanib plus lapatinib once daily at any doses studied were well tolerated in Japanese patients.

本文言語英語
ページ(範囲)673-683
ページ数11
ジャーナルCancer Chemotherapy and Pharmacology
73
4
DOI
出版ステータス出版済み - 04-2014
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 毒物学
  • 薬理学
  • 癌研究
  • 薬理学(医学)

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