Background. Many studies concerning molecular-biological markers in colorectal cancer (CRC) were performed over the past decade. Вcl-2 protein (B-cell lymphoma 2) was one of the most studied molecular-biological markers and attracted the attention of different specialties as on studying carcinogenesis and the relationship with prognosis. Aim. To study in details the characteristics of Bcl-2; to study Bcl-2 role in the mechanisms regulating apoptosis; to show update data concerning the prognostic significance of this protein in CRC. Materials and methods. To write this literature review we have studied domestic and foreign publications from Russian and international systems of search (PubMed, eLibrary, etc.) over the past 2-30 years. Results. The evaluation of the expression of antiapoptopic protein Вcl-2 in tumor can give additional information about the course of malignant process independently of therapeutic effects, the biological behaviour of the tumor: the rapidity of growth, the ability of invasion and metastasis (i.e. the prognosis of a disease). Conclusion. The results concerning the impact of abnormal expression of apoptosis inhibitor Вcl-2 on the course and prognosis of CRC have been accumulated in the scientific literature, but there have been only several studies, analyzing the relationship between Вcl-2 and metastasis of CRC and factors influencing the invasive potential of tumor cells. Nowadays, there is no consensus about the prognostic significance of protein Вcl-2 in patients with CRC. In some studies, concerning CRC, have been shown the correlation between Bcl-2 overexpression in tumor cells and a favorable course of disease and good survival in patients. Other authors have been shown that tumors with Bcl-2 overexpression, by contrast, are more aggressive in comparison with tumors without Bcl-2 expression. There are a number of studies in which the prognostic significance of Bcl-2 protein is not proved. Many issues, concerning the correlation between this molecular-biological marker and clinico-morphological characteristics of tumor, might also need to be itemized. All shown in the article is a subject to further research.
Background.The evaluation of clinical and morphological characteristics is not sufficient to predict the prognosis of metastatic colorectal cancer (mRCC). Tumor aggressiveness may vary significantly even in patients with similar clinical and morphological disease characteristics. These differences are believed to be associated with molecular tumor characteristics and can be used as additional prognostic factors for patient survival.Objective:to evaluate the effect of topoisomerase IIα overexpression (topoIIα) in primary colon tumor on the mRCC prognosis.Materials and methods. The study cohort included patients with mRCC that have not previously received treatment for disseminated disease. All participants had a morphologically verified diagnosis of colon adenocarcinoma and received first-line chemotherapy with oxaliplatin and capecitabine. We evaluated both short-term and long-term treatment outcomes. We also assessed the expression of topoIIα in primary colon tumors (biopsy/surgical specimens obtained prior to initiation of first-line treatment) using immunohistochemical methods. We aimed to evaluate the association between the level of topoIIα expression and short-term/long-term treatment outcomes. We analyzed the impact of topoIIα expression in the primary tumor on the efficacy of first-line chemotherapy, progression-free survival (PFS) and overall survival (OS) in patients with mRCC.Results. Immunohistochemical evaluation of topoIIα expression in the primary tumor was conducted for 39 patients with mRCC. We found no correlation between topoIIα expression and PFS, i.e. median PFS did not differ significantly between patients with topoIIα-positive and topoIIα-negative tumors (p >0.05). Individuals with low levels of topoIIα expression in the primary tumor and those with topoIIα-negative cancer demonstrated significantly higher OS than patients with topoIIα overexpression (median OS 16.30 ± 2.0 months; 95 % confidence interval 12.32–20.28 vs 7.7 ± 4.98 months; 95 % confidence interval 0.00–17.46; p = 0.007).Conclusion.Overexpression of topoIIα is a factor of poor prognosis associated with poorer OS in patients with mRCC that received first-line chemotherapy with oxaliplatin and capecitabine.
Today, the researchers continue the search for the most optimal regimens of drug therapy for metastatic colorectal cancer (mCRC) which are supposed to increase progression-free survival (PFS) and overall survival (OS), improve patient quality of life. Due to significant progress in chemotherapy (CT) and surgical treatment of mCRC, and the multidisciplinary approach, the treatment algorithms have changed. The increase in life expectancy of patients is observed when all three of the most active chemotherapy drugs in this disease: oxaliplatin (Oxa), irinotecan (Iri), fluoropyrimidines are administered. The inclusion of the targeted drug cetuximab in modern mCRC treatment regimens led to a statistically significant increase in the objective response rate (ORR), median PFS and OS. The article presents the results of the most significant clinical studies of the eficacy of the antiEGFR drug cetuximab in combination with standard CT regimens for the first- and second-line treatment of mCRC, and describes a clinical case of the successful use of cetuximab in mCRC therapy.
A study that enrolled 30 patients with advanced colorectal cancer, who had not previously received any specific drug treatment, was conducted to develop and study a three-component regimen with oral fluoropyrimidine tegafur (Ftorafur) in outpatient practice. The study evaluated the time to disease progression (TDP), the overall survival (OS) of patients, who received irinotecan + oxaliplatin + Ftorafur in the first-line therapy, as well as the effectiveness and safety of this regimen. 6 patients received a 3-week chemotherapy cycle (Fig. 1), 24 patients – a 2-week chemotherapy cycle (Fig. 2). The preliminary results of the study have been obtained. The median OS was not reached, the median TDP was 8.5 months. In Group I, there was partial regression of metastasis in 3/6 patients, and prolonged disease stabilization (≥ 6 months) in 3 patients. The therapeutic effect (partial remission + long-term stabilization ≥ 6 months) was observed in all patients. The duration of TDP was from 6 to 15 months. In group II, the effect was evaluated in 24 patients, who received at least 2 chemotherapy cycles. 14/24 patients had a partial response (PR), of which 4 (16.6%) patients were radically operated, 6 patients elicited disease stabilization. Thus, control over the disease was achieved in 83.33% of patients in Group II. Oxaliplatin combined with irinotecan and fluorafur was effective, had an acceptable toxicity profile, and therefore, can be used in debilitated patients with disseminated disease.
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