A phase I study of bevacizumab (B) in combination with everolimus (E) and erlotinib (E) in advanced cancer (BEE).
Cancer Chemother Pharmacol
; 67(2): 465-74, 2011 Feb.
Article
em En
| MEDLINE
| ID: mdl-21079958
ABSTRACT
PURPOSE:
VEGF, mTOR, and EGFR inhibitors have demonstrated anti-tumor and anti-angiogenic effects alone and in combination with each other. This study evaluated the safety, tolerability, and pharmacokinetics of bevacizumab, everolimus, and erlotinib combination.METHODS:
Doublet therapy consisted of bevacizumab at 10 mg/kg every 14 days and everolimus 5 mg daily which escalated to 10 mg daily. Erlotinib 75 mg daily was added to the phase II dose recommended phase II dose (RPTD) of bevacizumab and everolimus. Dose-limiting toxicity (DLT) was assessed in cycle 1.RESULTS:
Forty-eight patients with advanced solid malignancies were evaluable for DLT and efficacy. No DLTs were observed in the doublet dose escalation. Two DLTs (grade 3 mucositis and grade 3 rash) were observed with the addition of erlotinib 75 mg daily. Consequently, triplet doses were adjusted and were better tolerated. Four patients had a partial response. Median progression-free survival (PFS) for the doublet therapy was 6.0 months (0.5 to 32+ months) and 5.5 months (0.8 to 27+ months) for the triplet therapy. Systemic exposure of everolimus was significantly higher in combination with erlotinib (476 ± 161 ng h/mL) compared to when given alone (393 ± 156 ng h/mL; P = 0.020).CONCLUSIONS:
The RPTD for the doublet therapy is bevacizumab 10 mg/kg every 14 days and everolimus 10 mg daily, and the RPTD for the triplet therapy is bevacizumab 5 mg/kg every 14 days, everolimus 5 mg and erlotinib 75 mg daily. Prolonged disease stability was demonstrated in tumors known to respond to mTOR inhibition and potentially resistant to VEGF blockade.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinazolinas
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Protocolos de Quimioterapia Combinada Antineoplásica
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Sirolimo
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Anticorpos Monoclonais
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Neoplasias
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Ano de publicação:
2011
Tipo de documento:
Article