BACKGROUND: To evaluate the safety and tolerability of two different weekly 
doses of the fully humanized epidermal growth factor receptor (EGFR)-targeting 
monoclonal antibody matuzumab combined with high-dose 5-fluorouracil, leucovorin 
and cisplatin (PLF) in the first-line treatment of patients with EGFR-positive 
advanced gastric and esophagogastric adenocarcinomas.
METHODS: Patients were treated in two matuzumab dose groups with the first 
cohort of patients receiving 400 mg matuzumab in combination with PLF. Based on 
the safety observations the next cohort of patients received 800 mg matuzumab. 
The study was conducted in two parts, with phase A, designed to assess the 
safety and tolerability of the combination, and phase B designed to be a 
treatment continuation for those patients benefiting from treatment. Treatment 
cycles were 7 weeks each. Each patient received the dose of matuzumab they were 
assigned to at study entry for the duration of the study.
RESULTS: Fifteen EGFR-positive patients were enrolled into the two matuzumab 
dose groups; 400 mg dose n=7; 800 mg dose n=8. All patients experienced at least 
one adverse event (AE). No patient experienced any serious AE which was 
considered to be related to matuzumab. Two grade 3 AEs possibly related to 
matuzumab occurred in 2 different patients (13.3 %), both in the 800 mg dose 
group. No dose-limiting toxicity (DLT) was observed in the 400 mg group. The 
maximum tolerated dose of matuzumab was not reached. The best confirmed overall 
response rate was 26.7 %.
CONCLUSION: Matuzumab, in combination with PLF, demonstrated an acceptable 
safety profile with modest anti-tumor activity.