br CEA is a nonspecific
CEA is a nonspecific biomarker with abnormal KRN 7000 in several solid tumors including gastric cancer. Contradictory results concerning the prognostic effect of pretreatment CEA level have been reported.50-52 In our results, patients with high pretreatment serum CEA level were associated with shorter PFS and worse prognosis compared with patients having a normal level, consistent with the results in previous studies.53,54 Furthermore, in multivariable Cox regression model, CEA was found to be an independent factor associated with PFS.
The role of CA19-9 and CA72-4 is not well elucidated.53,54 Some studies found its prognostic value in surgically treated patients.29,55-57 Our studies have shown that the high serum CA19-9 had a significant effect on prognosis and could be used as an independent factor in poor prognosis (multivariable Cox regression model).
Previous study did not find any correlation of CA125 with PFS in gastric cancer patients.29 However, in our results, the difference in the PFS between high and normal pretreatment levels of CA125 was also not significant (P > 0.05). The value of CA72-4 is controversial in gastric cancer; however, in adenocarcinoma CA72-4 is widely accepted.54
The relationship between tumor markers and response to chemotherapy in breast, colorectal, ovarian, and pancreatic cancer has already been reported9,58; however, the significance of such tumor markers in the advanced stage of gastric cancer has not been explored thoroughly from clinical aspect.54,59
Our present study with a special focus on tumor biomarker response to palliative therapy, the mean level of tumor markers became significantly lower after palliative chemotherapy. The decrease in the mean level of CEA, CA19-9, and CA72-4 attain statistical significance (P = 0.02, P = 0.002, P =0.001, respectively) as compared with the disease progression group.
A previous study of first-line chemotherapy with or without antiangiogenic agents (Beva-cizumab, Trastuzumab, Nitaluzumab, Nidotuzumab) supports the hypothesis that antiangiogenic agents, ie, (Bevacizumab, Trastuzumab, Nitaluzumab, Nidotuzumab) improve drug delivery to the tumor.60-62 Our present study for the comparison of effective association of biomarkers with 2-drugs (first-line platinum-based therapy) and 3-drugs antiangiogenic agents, ie, (Beva-cizumab, Trastuzumab, Nitaluzumab, Nidotuzumab + Paclitaxel, carboplatin) regimens, we have found a significant decrease in the mean level of tumor markers CEA, CA19-9, and CA72-4 of patients using 3-drugs regimen as compare to patients taking 2-drugs regimen. Taken together,
these findings suggest that an appropriate addition of antiangiogenic agent, ie, (Bevacizumab, Trastuzumab, Nitaluzumab, Nidotuzumab) to first-line platinum-based chemotherapy may im-prove PFS as well as quality of life of cancer patients.
Although these biomarkers CEA, CA125, CA19-9, and CA 72-4 may not be an appropriate prognostic measure at individual level however a combination of these biomarkers may assist in the assessment of therapeutic and diagnostic measure of gastric cancer in advanced stage IV.63 Chiu et al reported in their study that the changes occurring in tumor markers (combination of CEA, CA125, and CA19-9) pre– and post–gefitinib-based chemotherapy) were in relation to tumor response and PFS,64 additionally serum CEA levels were found closely associated with advanced stage IV gastric cancer as promising biomarkers.65 So, the usage of tumor marker scores might play a promising role in diagnosis and in forecasting the outcome of gastric cancer in advanced stage IV.7,29,40,66
Current study highlights the combined positive detection (when 1 or more tumor markers are above the cut-off value) was associated with differentiation and clinical response and when ana-lyzed by Kaplan-Meier survival curve. We have found a significant decrease in the PFS of patients having 3 and/or 4 tumor markers elevated (pretreatment) compared with those patients having 0, 1, and/or 2 tumor markers elevated (pretreatment). And patients with more than 2 high pre-treatment tumor markers were less responsive to chemotherapy even if monocots were treated with 3-drugs regimen. Thus, oncologists should consider the value of these biomarkers before starting chemotherapy and prescribe a suitable combination of chemotherapy,7,40,67 analyzed by Kaplan-Meier survival curve. We have found a significant decrease in the PFS of patients having 3 and/or 4 tumor markers elevated (pretreatment) compared with those patients having 0, 1, and/or 2 tu-mor markers elevated (pretreatment). And patients with more than 2 high pretreatment tumor markers were less responsive to chemotherapy even if they were treated with 3-drugs regimen. Thus, oncologists should consider the value of these biomarkers before starting chemotherapy and prescribe a suitable combination of chemotherapy.23,68