Phase I evaluation of telatinib, a VEGF receptor tyrosine kinase inhibitor, in combination with bevacizumab in subjects with advanced solid tumors.
Ann Oncol
; 22(11): 2508-2515, 2011 Nov.
Article
em En
| MEDLINE
| ID: mdl-21378200
ABSTRACT
BACKGROUND:
Blocking both receptor and ligand of the vascular endothelial growth factor (receptor) VEGF(R) pathway might be feasible and increase antitumor activity. This phase I study investigated telatinib, an oral tyrosine kinase inhibitor targeting VEGFR-2, combined with bevacizumab, in adults with solid tumors. PATIENTS ANDMETHODS:
Twenty-six patients were treated in successive cohorts with telatinib (twice-daily continuously, 450-900 mg) or bevacizumab (bi-weekly, starting dose 5 mg/kg). Safety, pharmacokinetics, endothelial (progenitor) cell (E(P)C)/growth factor kinetics and efficacy were assessed.RESULTS:
Most frequent adverse events were pain, nausea, voice changes and fatigue. Five dose-limiting toxicities (DLTs) occurred hypertension (cohort I and II), bowel perforation, lipase increase and atrial flutter (cohort III). Cumulative toxicity resulted in a bevacizumab dose reduction to 1 mg/kg (cohort III). Due to three DLTs (n = 14), this cohort represented the best-tolerated dose level. Bevacizumab effectively neutralized plasma VEGF even at 1 mg/kg. Twelve patients had stable disease (clinical benefit 46%). EPC and SDF-1α levels increased during monotherapy telatinib.CONCLUSIONS:
Telatinib (450 mg b.i.d.) combined with bevacizumab (1 mg/kg bi-weekly) shows antitumor activity, but accumulating constitutional toxicity impedes long-term treatment of patients. Therefore, this combination will not be pursued in a phase II setting.
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Base de dados:
MEDLINE
Assunto principal:
Piridazinas
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Piridinas
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Proteínas Tirosina Quinases
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Protocolos de Quimioterapia Combinada Antineoplásica
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Receptor 1 de Fatores de Crescimento do Endotélio Vascular
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Anticorpos Monoclonais Humanizados
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Neoplasias
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article