Phase i dose-escalation study to determine the safety, pharmacokinetics and pharmacodynamics of brivanib alaninate in combination with full-dose cetuximab in patients with advanced gastrointestinal malignancies who have failed prior therapy

C. R. Garrett, L. L. Siu, A. El-Khoueiry, J. Buter, C. M. Rocha-Lima, J. Marshall, P. Lorusso, P. Major, J. Chemidlin, O. Mokliatchouk, L. Velasquez, W. Hayes, D. Feltquate, S. Syed, S. Ford, G. Kollia, S. Galbraith, D. S.A. Nuyten

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Background:The objectives of this phase I study were to determine the safety, pharmacokinetics (PK), pharmacodynamics and efficacy of brivanib combined with full-dose cetuximab in patients with advanced gastrointestinal malignancies.Methods:Patients with advanced gastrointestinal malignancies who had failed prior therapies received brivanib (320, 600 or 800 mg daily) plus cetuximab (400 mg m-2 loading dose then 250 mg m-2 weekly). Assessments included adverse events, PK, tumour response, 218Ffluoro-2-deoxyglucose positron-emitting tomography and K-Ras mutation analyses.Results:Toxicities observed were manageable; the most common treatment-related toxicities (10% of patients) were fatigue, diarrhoea, anorexia, increase in aspartate aminotransferase and alanine aminotransferase, acneiform dermatitis, headache, mucosal inflammation, nausea, dry skin, vomiting, hypertension, pruritus, proteinuria and weight loss. Of 62 patients, 6 (9.7%) had objective radiographic partial responses, with an overall response rate of 10%. Median duration of response was 9.2 months; median progression-free survival was 3.9 months.Conclusions:The acceptable toxicity profile and efficacy of brivanib observed in this study were promising. These findings are being further evaluated in a phase III study of brivanib plus cetuximab vs cetuximab alone in patients previously treated with combination chemotherapy for K-Ras wild-type advanced metastatic colorectal cancer.

Original languageEnglish (US)
Pages (from-to)44-52
Number of pages9
JournalBritish Journal of Cancer
Volume105
Issue number1
DOIs
StatePublished - Jun 28 2011

Keywords

  • antiangiogenesis
  • brivanib
  • cetuximab
  • gastrointestinal tumours

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Phase i dose-escalation study to determine the safety, pharmacokinetics and pharmacodynamics of brivanib alaninate in combination with full-dose cetuximab in patients with advanced gastrointestinal malignancies who have failed prior therapy'. Together they form a unique fingerprint.

  • Cite this

    Garrett, C. R., Siu, L. L., El-Khoueiry, A., Buter, J., Rocha-Lima, C. M., Marshall, J., Lorusso, P., Major, P., Chemidlin, J., Mokliatchouk, O., Velasquez, L., Hayes, W., Feltquate, D., Syed, S., Ford, S., Kollia, G., Galbraith, S., & Nuyten, D. S. A. (2011). Phase i dose-escalation study to determine the safety, pharmacokinetics and pharmacodynamics of brivanib alaninate in combination with full-dose cetuximab in patients with advanced gastrointestinal malignancies who have failed prior therapy. British Journal of Cancer, 105(1), 44-52. https://doi.org/10.1038/bjc.2011.182