Effects of lapatinib monotherapy: results of a randomised phase II study in therapy-naive patients with locally advanced squamous cell carcinoma of the head and neck
| Autor: | C Carracedo, L Downie, Iman El-Hariry, J. M. del Campo, P Sebastian, Natalie Compton, D Lokanatha, Stéphane Temam, J. H. Bourhis, Kevin J. Harrington, Ricardo Hitt, D Midwinter, Nigel Biswas-Baldwin, N Maroudias, D. de Raucourt, Christopher M. Nutting, Didier Cupissol |
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| Rok vydání: | 2011 |
| Předmět: |
Oncology
Adult Male squamous cell carcinoma Cancer Research medicine.medical_specialty Pathology medicine.medical_treatment Phases of clinical research Antineoplastic Agents Lapatinib Placebo Targeted therapy Placebos Internal medicine medicine Carcinoma Humans Single-Blind Method Epidermal growth factor receptor Neoplasms Squamous Cell Adverse effect skin and connective tissue diseases Neoadjuvant therapy Aged Aged 80 and over biology business.industry Squamous Cell Carcinoma of Head and Neck Middle Aged medicine.disease Neoadjuvant Therapy Treatment Outcome Head and Neck Neoplasms biology.protein Carcinoma Squamous Cell Disease Progression Quinazolines Clinical Study Female business epidermal growth factor receptor Algorithms medicine.drug |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 |
| Popis: | Background: Lapatinib is a dual inhibitor of epidermal growth factor receptor (EGFR) and human EGFR-2 (HER-2) tyrosine kinases. This study investigated the pharmacodynamic and clinical effects of lapatinib in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Methods: In total, 107 therapy-naive patients with locally advanced SCCHN were randomised (2 : 1) to receive lapatinib or placebo for 2–6 weeks before chemoradiation therapy (CRT). Endpoints included apoptosis and proliferation rates, clinical response, and toxicity. Results: Versus placebo, lapatinib monotherapy did not significantly increase apoptosis detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labelling or caspase-3 assays. A statistically significant decrease in proliferation using Ki67 assay was observed (P=0.030). In a subset of 40 patients that received ⩾4 weeks of lapatinib or placebo, objective response rate (ORR) was 17% (n=4/24) vs 0% (n=0/16). In the lapatinib single-agent responders, all had EGFR overexpression, 50% had EGFR amplification, and 50% had HER2 expression by immunohistochemistry (including one patient with HER2 amplification). However, these patients showed variable modulation of apoptosis, proliferation, and phosphorylated EGFR on drug treatment. Following CRT, there was a statistically non-significant difference in ORR between lapatinib (70%) and placebo (53%). There was no clear correlation between changes in apoptosis or proliferation and response to chemoradiation. Mucosal inflammation, asthenia, odynophagia, and dysphagia were the most commonly reported adverse events with lapatinib. Conclusion: Short-term lapatinib monotherapy did not demonstrate apoptotic changes, but provided evidence of clinical activity in locally advanced SCCHN, and warrants further investigation in this disease. |
| Databáze: | OpenAIRE |
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