Antitumor activity and biomarker analysis of sunitinib in patients with bevacizumab-refractory metastatic renal cell carcinoma.
J Clin Oncol
; 26(22): 3743-8, 2008 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-18669461
ABSTRACT
PURPOSE:
To assess the safety and efficacy of sunitinib in patients with bevacizumab-refractory metastatic renal cell carcinoma (mRCC) and explore biomarkers for sunitinib response. PATIENTS ANDMETHODS:
Patients with mRCC and disease progression after bevacizumab-based therapy received oral sunitinib 50 mg once daily in 6-week cycles on a 4/2 schedule (4 weeks with treatment followed by 2 weeks without treatment) in a phase II multicenter study. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), duration of response (DR), overall survival (OS), and safety. Plasma soluble proteins (vascular endothelial growth factor [VEGF]-A, VEGF-C, soluble VEGF receptor [sVEGFR]-3, and placental growth factor [PlGF]) levels were measured.RESULTS:
Sixty-one patients were enrolled. The ORR was 23.0% (95% CI, 13.2% to 35.5%), median PFS was 30.4 weeks (95% CI, 18.3 to 36.7 weeks), median DR was 44.1 weeks (95% CI, 25.0 to 102.7 weeks), and median OS was 47.1 weeks (95% CI, 36.9 to 79.4 weeks). Mean plasma VEGF-A and PlGF levels significantly increased whereas VEGF-C and sVEGFR-3 levels decreased with sunitinib treatment. Lower baseline levels of sVEGFR-3 and VEGF-C were associated with longer PFS and ORR. Most treatment-related adverse events were of mild-to-moderate intensity and included fatigue, hypertension, and hand-foot syndrome.CONCLUSION:
Sunitinib has substantial antitumor activity in patients with bevacizumab-refractory mRCC and modulates circulating VEGF pathway biomarkers. These data support the hypothesis that sunitinib inhibits signaling pathways involved in bevacizumab resistance. Baseline levels of sVEGFR-3 and VEGF-C may have potential utility as biomarkers of clinical efficacy in this setting.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirróis
/
Carcinoma de Células Renais
/
Biomarcadores Tumorais
/
Resistencia a Medicamentos Antineoplásicos
/
Inibidores da Angiogênese
/
Indóis
/
Neoplasias Renais
/
Anticorpos Monoclonais
Tipo de estudo:
Clinical_trials
/
Observational_studies
/
Risk_factors_studies
País/Região como assunto:
America do norte
Idioma:
En
Revista:
J Clin Oncol
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos