Abstract
The purpose of this study was to analyze the predictive value of neutrophil/lymphocyte ratio (NLR) to better clarify which patient groups will benefit the most from particular treatments like bevacizumab. A total of 245 treatment-naive metastatic colorectal cancern (mCRC) patients were retrospectively enrolled and divided into 2 groups: 145 group A patients were treated with chemotherapy in combination with bevacizumab, and 100 group B patients were treated as above without bevacizumab. Group A patients had better median overall survival (OS) and progression-free survival (PFS) (24.0 and 9.0 months) than group B patients (20 and 6.0 months) (p=0.033; p=0.015). In patients with low NLR, OS and PFS were significantly longer in group A patients (27 vs 18 months, p=0.001; 11 vs 7 months, p=0.017). We conclude that NLR, a basal cancer related inflammation marker, is associated with the resistance to bevacizumab- based treatments in mCRC patients.
Highlights
For several years, the standard treatment for metastatic colorectal cancer patients, has been the addition of irinotecan, oxaliplatin, or both to 5-fluorouracil (5-FU)based chemotherapy (Ducreux et al, 2007)
The results from randomized phase III clinical trials conducted across the world showed that when bevacizumab was added to chemotherapies in the first line treatment, progression-free survival (PFS) and overall survival (OS) of metastatic colorectal cancern (mCRC) patients was 8.6-10.6 months and 20.3-25.9 months respectively (Hurwitz et al, 2004; Fuchs et al, 2007; Saltz et al, 2008; Van Cutsem et al, 2009; Stathopoulos et al, 2010)
PFS improvement was observed when bevacizumab was added to oxaliplatinbased regimens (XELOX or FOLFOX) while no benefit was observed in OS. (FOLFOX/XELOX 8.0 months vs FOLOFX/XELOX+Bevacizumab 9.4 months, p=0.0023)
Summary
The standard treatment for metastatic colorectal cancer (mCRC) patients, has been the addition of irinotecan, oxaliplatin, or both to 5-fluorouracil (5-FU)based chemotherapy (Ducreux et al, 2007). For mCRC patients, bevacizumab is very active and improves outcomes when used with a variety of first-line and second-line regimens (Giantonio et al, 2007; Fuchs et al, 2008). Against this data, there are studies which showed that bevacizumab did not improve overall survival when added to standard chemotherapy (Stathopoulos et al, 2010; Price et al, 2012). In NO19666 study, only the subgroup analysis demonstrated an improvement in progression free survival of mCRC patients that were treated by the addition of bevacizumab to XELOX (capecitabine+oxaliplatin) (Saltz et al, 2009). There are no other randomized trials comparing the outcomes between chemotherapy and chemotherapy plus bevacizumab Another problem with bevacizumab is the absence of the clinically available predictive marker. Conclusions: We conclude that NLR, a basal cancer related inflammation marker, is associated with the resistance to bevacizumabbased treatments in mCRC patients.
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