BACKGROUND: Epidermal growth factor receptor (EGFR) is overexpressed in 80%-90% 
of non-small-cell lung cancer (NSCLC). Matuzumab, a humanized immunoglobulin 
G(1) (IgG(1)) anti-EGFR monoclonal antibody, blocks activation of EGFR. 
Paclitaxel and EGFR inhibitors have additive antitumour effects in vitro. This 
phase I study assessed the tolerability, pharmacokinetics and efficacy of the 
combination of matuzumab and paclitaxel in patients with advanced NSCLC.
MATERIALS AND METHODS: Eighteen chemotherapy-naïve (n = 9) or pretreated (n = 9) 
patients with stage IIIB or IV EGFR-positive NSCLC received weekly doses of 
matuzumab (100, 200, 400 or 800 mg) followed by paclitaxel 175 mg/m(2) every 3 
weeks. Toxicity was evaluated weekly and pharmacokinetics were measured during 
cycles 1 and 2.
RESULTS: The maximum planned matuzumab dose of 800 mg was achieved without 
reaching the maximum tolerated dose. Grade 4 neutropenia occurred in one of 
three patients at 800 mg but resolved within 1 week; five additional patients 
treated with 800 mg had no dose-limiting toxicity (DLT). Grade 1/2 acneiform 
skin rash in 14 patients was the most frequent matuzumab-related side-effect. 
There were no higher-grade adverse events. Grade 2 toxicities included pruritus 
(n = 2), bronchospasm (n = 1), fissures (n = 1), abdominal pain (n = 1) and hot 
flushes (n = 1). Paclitaxel was discontinued in four patients due to allergic 
reactions. Coadministration of paclitaxel did not alter matuzumab 
pharmacokinetics. Responses occurred in four of 18 patients and included one 
complete response.
CONCLUSIONS: Matuzumab doses up to 800 mg weekly with paclitaxel 175 mg/m(2) 
every 3 weeks are well tolerated, with no apparent drug interactions and with 
evidence of antitumor activity.