Prognostic/predictive value of 207 serum factors in colorectal cancer treated with cediranib and/or chemotherapy
Menée à partir d'échantillons sériques prélevés sur 582 patients atteints d'un cancer colorectal métastatique et inclus dans un essai randomisé de phase III évaluant une chimiothérapie avec ou sans cédiranib, cette étude évalue, du point de vue de la survie sans progression et de la survie globale, la valeur pronostique et prédictive de 207 protéines (IL-6, IL-8, protéine C réactive, antigène carcino-embryonnaire, VEGF,...)
Background : The prognostic and predictive value of multiple serum biomarkers was evaluated using samples from a randomised phase III study (HORIZON II) investigating chemotherapy with or without cediranib in metastatic colorectal cancer (mCRC).
Methods : Baseline levels of 207 protein markers were measured in serum samples from 582 HORIZON II (FOLFOX/XELOX plus cediranib 20 mg (n=330) or placebo (n=252)) patients. Median baseline values of each biomarker were used to categorise patients as high or low. Markers were then assessed for their association with efficacy, defined by progression-free survival (PFS) and overall survival (OS). A generalised boosted regression model identified markers of particular interest.
Results : Correlation of protein levels with PFS and OS suggested that multiple factors had a prognostic value, independent of treatment arm, including IL-6, IL-8, C-reactive protein (CRP), ICAM-1 and carcinoembryonic antigen (CEA). Among the angiogenesis regulators, low levels of vascular endothelial growth factor (VEGF), VEGF-D, VEGFR-1, VEGFR-3, NRP1 and Tie-2 correlated with better outcome.
Conclusion : This large data set generated using serum samples from mCRC patients treated with chemotherapy and VEGF inhibitors, defines baseline characteristics for 207 serum proteins. Multiple prognostic factors were identified that could be disease related or predict which patients derive most benefit from 5-fluorouracil (5-FU)-based chemotherapy, meriting further exploration in prospective studies.
British Journal of Cancer , résumé, 2012