Annals of Oncology Advance Access originally published online on March 13, 2006
Annals of Oncology 2006 17(6):1007-1013; doi:10.1093/annonc/mdl042
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© 2006 European Society for Medical Oncology
A phase I study of the humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody EMD 72000 (matuzumab) in combination with paclitaxel in patients with EGFR-positive advanced non-small-cell lung cancer (NSCLC)
1 Department of Hematology/Oncology, University of Tuebingen, 72076 Tuebingen, Germany; 2 Division of Medical Oncology, British Columbia Cancer Agency - Vancouver Cancer Center, Vancouver, Canada; 3 Merck KGaA, Darmstadt; 4 Department of Oncology, Hematology, Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, Germany
* Correspondence to: Dr C. Bokemeyer, Department of Oncology/Hematology, Bone Marrow Transplantation, University Medical Center Hamburg Eppendorf, Martinistraße 52, 20246 Hamburg, Germany. Tel: +49-40-42803-2960; Fax: +49-40-42803-8054; E-mail: c.bokemeyer{at}uke.uni-hamburg.de
Background: Epidermal growth factor receptor (EGFR) is overexpressed in 80%–90% of non-small-cell lung cancer (NSCLC). Matuzumab, a humanized immunoglobulin G1 (IgG1) 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/m2 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/m2 every 3 weeks are well tolerated, with no apparent drug interactions and with evidence of antitumor activity.
Key words: EMD 72000, matuzumab, lung cancer, paclitaxel, phase I
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