ABSTRACT
PURPOSE: Unlike cetuximab, there is a paucity of biomarkers for bevacizumab as predictors of outcome in metastatic colorectal cancer (mCRC) patients. Obviously exploring the worth of some potential markers in this setting is warranted. The purpose of this study was to investigate the predictive value of the presence of K-RAS and B-RAF mutations on the outcome of patients with mCRC treated with FOLFIRI and bevacizumab combination therapy. METHODS: A total of 172 patients with mCRC were evaluated. K-RAS and B-RAF mutations were analyzed by quantitative PCR. Median progression-free survival (PFS) and overall survival (OS) were compared utilizing chi-square and Mann-Whitney U tests, respectively. RESULTS: Forty-four percent (N=77) of the patients were found to harbor K-RAS mutations and 6 (7.5%) were positive for B-RAF mutations. In baseline no difference in PFS and OS was observed between the groups with or without K-RAS mutation. No relationship was established between K-RAS and B-RAF mutation status and baseline CEA and CA19-9 tumor markers levels. CONCLUSION: K-RAS and B-RAF mutations do not seem to be predictive of treatment outcome as potential biomarkers for bevacizumab therapy in mCRC. However, not only the presence of K-RAS and B-RAF mutations but also the different biological behavior of the various subtypes of mutations should be considered as potential determinants in the final outcome of this disease.
Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/genetics , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Biomarkers, Tumor/genetics , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Mutation , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins/genetics , ras Proteins/genetics , Adenocarcinoma/enzymology , Adenocarcinoma/mortality , Adenocarcinoma/secondary , Adenocarcinoma, Mucinous/drug therapy , Adenocarcinoma, Mucinous/enzymology , Adenocarcinoma, Mucinous/genetics , Adenocarcinoma, Mucinous/mortality , Adenocarcinoma, Mucinous/secondary , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/administration & dosage , Bevacizumab , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Chi-Square Distribution , Colorectal Neoplasms/enzymology , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , DNA Mutational Analysis , Disease-Free Survival , Female , Fluorouracil/administration & dosage , Genetic Predisposition to Disease , Humans , Kaplan-Meier Estimate , Leucovorin/administration & dosage , Male , Middle Aged , Patient Selection , Phenotype , Precision Medicine , Proto-Oncogene Proteins p21(ras) , Retrospective Studies , Time Factors , Treatment OutcomeABSTRACT
The first Phase I Trial with a combination of IL-2 and IFN-alpha was published in 1989. There are still some questions though, concerning the in vivo effects of this combination on lymphocytes. We designed a prospective pilot study to evaluate in vivo effects of low dose IL-2 and IFN-alpha combination on expression of Bcl-2, FAS (Apo-1/CD 95), Fas Ligand, IL-2 receptor (CD25), and HLA-DR on peripheral lymphocytes in patients with advanced renal cell carcinoma. After initiation of the immunomodulating therapy, Bcl-2 expressing lymphocytes increased significantly on day 3 (p < 0.025), Fas (Apo-1/CD95) expressing lymphocyte increased significantly on day 5 (p < 0.003), Fas ligand expressing lymphocytes increased significantly on day 3 (p < 0.004), HLA-DR expressing lymphocytes increased significantly on day 5 (p < 0.003), and IL-2 receptor (CD25) expressing cells increased significantly on day 5 (p < 0.01). We conclude that immunomodulating therapy induces in vivo expression of Bcl-2, Fas (Apo-1) and Fas Ligand in lymphocytes significantly.
