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 language | English |
|---|---|
| Pages (from-to) | 44-52 |
| Number of pages | 9 |
| Journal | British Journal of Cancer |
| Volume | 105 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jun 28 2011 |
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Keywords
- antiangiogenesis
- brivanib
- cetuximab
- gastrointestinal tumours
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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. / 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.
In: British Journal of Cancer, Vol. 105, No. 1, 28.06.2011, p. 44-52.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Garrett, C. R.
AU - Siu, L. L.
AU - El-Khoueiry, A.
AU - Buter, J.
AU - Rocha-Lima, C. M.
AU - Marshall, J.
AU - Lorusso, P.
AU - Major, P.
AU - Chemidlin, J.
AU - Mokliatchouk, O.
AU - Velasquez, L.
AU - Hayes, W.
AU - Feltquate, D.
AU - Syed, S.
AU - Ford, S.
AU - Kollia, G.
AU - Galbraith, S.
AU - Nuyten, D. S A
PY - 2011/6/28
Y1 - 2011/6/28
N2 - 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.
AB - 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.
KW - antiangiogenesis
KW - brivanib
KW - cetuximab
KW - gastrointestinal tumours
UR - http://www.scopus.com/inward/record.url?scp=79959699570&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79959699570&partnerID=8YFLogxK
U2 - 10.1038/bjc.2011.182
DO - 10.1038/bjc.2011.182
M3 - Article
C2 - 21629245
AN - SCOPUS:79959699570
VL - 105
SP - 44
EP - 52
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 1
ER -