PURPOSE: This Phase I study determined the maximum-tolerated dose (MTD) of 
afatinib (Afatinib is an investigational compound and its safety and efficacy 
have not yet been established) (BIBW 2992; trade name not yet approved by FDA), 
an irreversible inhibitor of epidermal growth factor receptor (EGFR)/human 
epidermal growth factor receptor (HER)1 and 2, up to a dose of 50 mg/day in 
advanced non-small cell lung cancer (NSCLC), to establish the recommended dose 
for Phase II.
METHODS: Patients with advanced NSCLC who had received prior platinum-doublet 
chemotherapy and/or erlotinib/gefitinib therapy, or who were ineligible for, or 
not amenable to, treatment with established therapies, received oral afatinib 
once daily. The MTD was determined based on dose-limiting toxicities (DLTs); 
other assessments included safety, pharmacokinetic profile, antitumour activity 
according to response evaluation criteria in solid tumours and EGFR/HER1 
mutation analysis where possible.
RESULTS: Twelve evaluable patients were treated at doses of 20-50 mg/day. One 
DLT was observed at 50 mg/day in Course 1 (Grade 3 mucositis). The most frequent 
drug-related adverse events were diarrhoea, dry skin, stomatitis, rash, 
paronychia and anorexia; most were Grade 1 or 2. Six out of 12 patients had 
tumour size reductions; durable stable disease was achieved in three patients 
including one with EGFR/HER1 exon 19 and T790 M mutations. Peak plasma 
concentrations of afatinib were reached 3-4 h after administration and declined 
with a half-life of 30-40 h. Afatinib 50 mg/day was well tolerated with an 
acceptable safety profile during Phase I.
CONCLUSION: Recommended dose for Phase II was defined as 50 mg/day for Japanese 
patients; the same as for non-Japanese patients.