Phase I dose-escalation and pharmacokinetic trial of lapatinib (GW572016), a selective oral dual inhibitor of ErbB-1 and -2 tyrosine kinases, in Japanese patients with solid tumors

Kazuhiko Nakagawa, Hironobu Minami, Masayuki Kanezaki, Akihira Mukaiyama, Yoshiyuki Minamide, Hisao Uejima, Takayasu Kurata, Toshiji Nogami, Kenji Kawada, Hirofumi Mukai, Yasutsuna Sasaki, Masahiro Fukuoka

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Objective: The Phase I dose-escalation study was conducted to evaluate the safety and pharmacokinetics of lapatinib (GW572016), a dual ErbB-1 and -2 inhibitor, in Japanese patients with solid tumors that generally express ErbB-1 and/or overexpress ErbB-2. Methods: Patients received oral lapatinib once daily until disease progression or in an event of unacceptable toxicity. Results: Twenty-four patients received lapatinib at dose levels of 900, 1200, 1600 and 1800 mg/day; six subjects enrolled to each dose level. The majority of drug-related adverse events was mild (Grade 1-2); the most common events were diarrhea (16 of 24; 67%), rash (13 of 24; 54%) and dry skin (8 of 24; 33%). No Grade 4 adverse event was observed. There were four Grade 3 drug-related adverse events in three patients (i.e. two events of diarrhea at 1600 and 1800 mg/day each and γ-glutamyl transpeptidase increase at 1800 mg/day). The maximum tolerated dose was 1800 mg/day. The pharmacokinetic profile of lapatinib in Japanese patients was comparable to that of western subjects. Conclusions: Lapatinib was well tolerated at doses of 900-1600 mg/day in Japanese solid tumor patients. Overall, our findings were similar to those of overseas studies.

Original languageEnglish
Pages (from-to)116-123
Number of pages8
JournalJapanese journal of clinical oncology
Volume39
Issue number2
DOIs
Publication statusPublished - 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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