Identification of predictive circulating biomarkers of bevacizumab-containing regimen efficacy in pre-treated metastatic colorectal cancer patients.
BACKGROUND
To identify whether circulating levels of angiogenesis-related factors may be predictive of bevacizumab efficacy in pre-treated metastatic colorectal cancer (mCRC) patients.


METHODS
Pre-treatment serum levels of 24 cytokines were measured using a multiplex bead assay (MBA) in 32 pre-treated mCRC patients treated with irinotecan plus bevacizumab-based salvage therapy. Macrophage-derived chemokine (MDC), interleukins (ILs) 8 and 6 levels were also validated by enzyme-linked immunosorbent assay (ELISA) at different time points during therapy.


RESULTS
Higher epidermal growth factor (EGF) and MDC baseline levels (2.2- and 1.4-fold, respectively) and lower IL-10, IL-6 and IL-8 levels (0.2-, 0.6-, and 0.6-fold, respectively, P<0.05) were observed in patients responding to therapy. Baseline levels of these five serum factors compose a risk signature that may define the subset of patients most likely to benefit from bevacizumab-based therapy in terms of response rate and survival times. A positive correlation was found between MBA and ELISA results (P<0.01). Treatment exposure increased MDC and had opposite effects on IL-8 levels, which were decreased (P<0.05).


CONCLUSIONS
This study suggests that a set of inflammatory and angiogenesis-related serum markers may be associated with the efficacy of bevacizumab-containing regimen.
Laboratory of Pharmacogenomics, Division of Oncology, Center for Applied Medical Research, University of Navarra, Pamplona, Spain.
A
A
Abajo
V
V
Boni
I
I
Lopez
M
M
Gonzalez-Huarriz
N
N
Bitarte
J
J
Rodriguez
R
R
Zarate
E
E
Bandres
J
J
Garcia-Foncillas
D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000097:blood*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D054422:Chemokine CCL22 / Q000378:metabolism; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy*; D004815:Epidermal Growth Factor / Q000378:metabolism; D005260:Female; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged
D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D054422:Chemokine CCL22; D007378:Interleukins; D000068258:Bevacizumab; D004815:Epidermal Growth Factor; D000077146:Irinotecan; D002166:Camptothecin