Serum VEGF-A and CCL5 levels as candidate biomarkers for efficacy and toxicity of regorafenib in patients with metastatic colorectal cancer

Abstract

Regorafenib is an oral multi-kinase inhibitor used as salvage therapy for metastatic colorectal cancer (mCRC). We tested whether serum cytokine levels are associated with clinical outcome in the mCRC patients receiving regorafenib. Serum samples were collected before treatment start, day 21, and progressive disease, and eleven angiogenic and inflammatory cytokine serum levels were examined. Fifty-four patients of a total of 62 enrolled patients were eligible for the analyses. The chemokine ligand 5 (CCL5) levels ≤ cut-off value (59959 pg/ml) at baseline was associated with relative tumor shrinkage (P = 0.021), better progression-free survival (PFS) (P = 0.036) and overall survival (OS) (P = 0.019). Vascular endothelial growth factor A (VEGF-A) levels showing a decrease on day 21 were significantly associated with a better PFS (P = 0.021). CCL5 levels ≤ cut-off was associated with any grade hand-foot skin reaction (HFSR) (P = 0.025) and thrombocytopenia (P = 0.013). Low chemokine ligand 2 levels at baseline were associated with grade 2 ≤ HFSR. High angiopoietin-2 and basic fibroblast growth factor (bFGF) levels at baseline were associated with grade 3 ≤ total bilirubin increase and transaminases increase, respectively. Low bFGF levels at baseline were associated with grade 3 ≤ hypertension. No correlation with severe events was observed. Baseline serum CCL5 levels and decrease of the serum VEGF-A levels may serve as potential predictive markers for survival or treatment-specific toxicities in mCRC patients receiving regorafenib.

Serum CA19-9 Response Is an Early Predictive Marker of Efficacy of Regorafenib in Refractory Metastatic Colorectal Cancer

“…Certain studies have examined biomarkers of efficacy for regorafenib [6,7] , but no pretreatment biomarker that is useful and convenient in clinical practice has been identified yet. Therefore, we investigated whether early clinical symptomatic or biochemical changes could be predictive markers of the efficacy of regorafenib.…”

CCL5 mediates target‐kinase independent resistance to FLT3 inhibitors in FLT3‐ITD‐positive AML

“…In addition, CCL5 was found to contribute to tumor progression and metastasis (Azenshtein et al , ; Velasco‐Velázquez et al , ). Importantly, CCL5 was identified in several cancers as a useful biomarker for predicting treatment response and disease progression (Suenaga et al , ).…”

Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: The TRIBUTE analysis

“…Many clinical and biological variables have been analysed in order to better identify patients more likely to achieve an improved clinical outcome from this treatment. Unfortunately, to date, no predictive marker has been validated for the clinical practice78910. An interesting area of research in this setting is also represented by the potential role of off-target effects of different targeted agents to affect clinical outcome.…”