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.
Br J Cancer
; 105(1): 44-52, 2011 Jun 28.
Article
de En
| MEDLINE
| ID: mdl-21629245
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, 2[18F]fluoro-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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Triazines
/
Thérapie de rattrapage
/
Alanine
/
Tumeurs gastro-intestinales
/
Anticorps monoclonaux
Limites:
Adult
/
Aged
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Female
/
Humans
/
Male
/
Middle aged
Langue:
En
Journal:
Br J Cancer
Année:
2011
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique