BACKGROUND-Patients with advanced urothelial carcinoma that progresses after platinumbased chemotherapy have a poor prognosis and limited treatment options.
VFL demonstrates a survival advantage in second-line treatment for advanced TCCU. Consistency of results exists with significant and meaningful benefit over all efficacy parameters. Safety profile is acceptable, and therefore, VFL seems to be a reasonable option for TCCU progressing after first-line platinum-based therapy.
PURPOSE The present study sought to identify pretreatment prognostic factors for overall survival (OS) in patients with metastatic transitional cell carcinoma of the urothelial tract (TCCU) who experienced treatment failure with the first-line, platinum-based regimen included in the phase III vinflunine trial. PATIENTS AND METHODS In total, 370 patients with platinum-refractory TCCU were included in this analysis. Potential prognostic factors were recorded prospectively. Univariate analysis was used to identify clinical and laboratory factors that significantly impact survival. Multivariate analysis was used to identify independent prognostic factors, and bootstrap analysis was performed for internal validation, forming a prognostic model. External validation was performed on the phase II vinflunine study CA183001. RESULTS Multivariate analysis and the internal validation identified Eastern Cooperative Oncology Group performance status (PS) more than 0, hemoglobin level less than 10 g/dL, and the presence of liver metastasis as the main adverse prognostic factors for OS. External validation confirmed these prognostic factors. Four subgroups were formed based on the presence of zero, one, two, or three prognostic factors; the median OS times for these groups were 14.2, 7.3, 3.8, and 1.7 months (P < .001), respectively. CONCLUSION We identified and both internally and externally validated three adverse risk factors (PS, hemoglobin level, and liver metastasis) that predict for OS and developed a scoring system that classifies patients with platinum-refractory disease on second-line chemotherapy into four risk groups with different outcome. Similar to the first-line setting, the presence of visceral metastases and poor PS predict a worse prognosis. These factors, together with low hemoglobin, can be used for prognostication and future patient stratification in clinical trials.
BackgroundMicro RNAs are small, non-coding, single-stranded RNAs that negatively regulate gene expression at the post-transcriptional level. Since miR-143 was found to be down-regulated in prostate cancer cells, we wanted to analyze its expression in human prostate cancer, and test the ability of miR-43 to arrest prostate cancer cell growth in vitro and in vivo.ResultsExpression of miR-143 was analyzed in human prostate cancers by quantitative PCR, and by in situ hybridization. miR-143 was introduced in cancer cells in vivo by electroporation. Bioinformatics analysis and luciferase-based assays were used to determine miR-143 targets. We show in this study that miR-143 levels are inversely correlated with advanced stages of prostate cancer. Rescue of miR-143 expression in cancer cells results in the arrest of cell proliferation and the abrogation of tumor growth in mice. Furthermore, we show that the effects of miR-143 are mediated, at least in part by the inhibition of extracellular signal-regulated kinase-5 (ERK5) activity. We show here that ERK5 is a miR-143 target in prostate cancer.ConclusionsmiR-143 is as a new target for prostate cancer treatment.
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