Phase i study of bortezomib and cetuximab in patients with solid tumours expressing epidermal growth factor receptor

A. Z. Dudek, K. Lesniewski-Kmak, N. J. Shehadeh, O. N. Pandey, M. Franklin, R. A. Kratzke, E. W. Greeno, P. Kumar

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Bortezomib inhibits nuclear factor-B (NF-B). Cetuximab is a chimeric mouse-human antibody targeted against epidermal growth factor receptor (EGFR). We hypothesised that concomitant blockade of NF-B and EGFR signalling would overcome EGFR-mediated resistance to single-agent bortezomib and induce apoptosis through two molecular pathways. The aim of this phase I trial was to establish the maximum tolerated dose (MTD) for bortezomib plus cetuximab in patients with EGFR-expressing epithelial tumours. The 21-day treatment cycle consisted of bortezomib administered on days 1 and 8 through dose escalation (1.3-2 mg m 2). Cetuximab was delivered at a dose of 250 mg m 2 on days 1, 8 and 15 (400 mg m 2 day 1 cycle 1). A total of 37 patients were enroled and given a total 91 cycles. No grade 3 haematological toxicity was noted. Non-hematological grade 3 toxicities included fatigue (22% of patients), dyspnoea (16%) and infection (11%). The MTD was not reached at the highest tested bortezomib dose (2.0 mg m 2). Efficacy outcomes included disease progression in 21 patients (56.7%) and stable disease (SD) at 6 weeks in 16 patients (43.3%). Five of the six patients with SD at 12 weeks were diagnosed with cancers of the lungs or head and neck. This combination therapy was moderately effective in extensively pretreated patients with non-small cell lung or head and neck cancers and warrants further investigation.

Original languageEnglish (US)
Pages (from-to)1379-1384
Number of pages6
JournalBritish Journal of Cancer
Volume100
Issue number9
DOIs
StatePublished - May 5 2009

Keywords

  • Bortezomib
  • Cetuximab
  • EGFR
  • Epithelial solid tumours
  • Proteasome inhibition

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Dudek, A. Z., Lesniewski-Kmak, K., Shehadeh, N. J., Pandey, O. N., Franklin, M., Kratzke, R. A., Greeno, E. W., & Kumar, P. (2009). Phase i study of bortezomib and cetuximab in patients with solid tumours expressing epidermal growth factor receptor. British Journal of Cancer, 100(9), 1379-1384. https://doi.org/10.1038/sj.bjc.6605043