RESUMEN
BACKGROUND: Bevacizumab prolongs progression-free survival (PFS) in patients with metastatic colorectal cancer. We analysed the protein expression levels of vascular endothelial growth factor (VEGF) ligands and receptors to determine their prognostic and predictive effects. METHODS: We graded expression of VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-R1, and VEGF-R2 to assess whether overexpression predicted bevacizumab resistance in samples from 268 of 471 patients randomised to capecitabine (C), capecitabine and bevacizumab (CB), or CB and mitomycin (CBM) in the MAX trial and extended the analysis to the CAIRO-2 population. RESULTS: Patients with low expression of VEGF-D (0, 1þ) benefited from bevacizumab treatment (PFS hazard ratio (HR) (C vs CBþCBM), 0.21; 95% CI, 0.080.55; overall survival (OS) HR, 0.35; 95% CI, 0.130.90). Patients with higher VEGF-D expression received less benefit (VEGF-D 2þ PFS HR, 0.67; 95% CI, 0.451.00; OS HR, 0.82; 95% CI, 0.521.30; VEGF-D 3þ PFS HR, 0.77; 95% CI, 0.501.17; OS HR, 1.28; 95% CI, 0.792.09) (P interaction o0.05). In CAIRO-2, there was no difference in PFS or OS according to VEGF-D expression. CONCLUSIONS: The predictive value of VEGF-D expression for bevacizumab may depend on the chemotherapy backbone used. Further evaluation is required before clinical utilisation.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Factor D de Crecimiento Endotelial Vascular/metabolismo , Anticuerpos Monoclonales Humanizados/administración & dosificación , Bevacizumab , Capecitabina , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Mitomicina/administración & dosificación , Metástasis de la NeoplasiaRESUMEN
Crizotinib is a potent small-molecule inhibitor of ALK tyrosine kinase receptor (anaplastic lymphoma kinase; ALK) and hepatocyte growth factor receptor (HGF receptor, proto-oncogene c-Met). A range of tumors, including subsets of non-small cell lung cancer (NSCLC), anaplastic large cell lymphoma and inflammatory myofibroblastic tumors harbor an ALK rearrangement that leads to oncogenic activation of ALK. Crizotinib has demonstrated preclinical and clinical activity against such malignancies through inhibition of ALK, and patients harboring ALK- rearranged NSCLC have demonstrated high response rates and prolonged progression-free survival in phase I and II studies. In August 2011, crizotinib was approved for the treatment of advanced ALK-positive NSCLC.