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01.04.2014 | Original Article

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

verfasst von: 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

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 4/2014

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Abstract

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.

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Titel: Phase 1 study of pazopanib alone or combined with lapatinib in Japanese patients with solid tumors
verfasst von: 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
Publikationsdatum: 01.04.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 4/2014
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-014-2374-3

Springer Medizin

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