Japanese Journal of Clinical Oncology Advance Access originally published online on December 3, 2008
Japanese Journal of Clinical Oncology 2009 39(2):116-123; doi:10.1093/jjco/hyn135
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© The Author (2008). Published by Oxford University Press. All rights reserved
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
1 Kinki University School of Medicine, Osaka
2 National Cancer Center Hospital East, Chiba
3 GlaxoSmithKline, Tokyo
4 Saitama Medical School, Saitama, Japan
For reprints and all correspondence: Kazuhiko Nakagawa, Kinki University School of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-0014, Japan. E-mail: nakagawa{at}med.kindai.ac.jp
Received August 24, 2008; accepted October 30, 2008
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 
-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.
Key Words: ErbB-1 • ErbB-2 • lapatinib • phase I • tyrosine kinase inhibitor
Present address: Kobe University Hospital and Graduate School of Medicine, Hyogo, Japan