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
gamma-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.
