Background: Activating mutations in the epidermal growth factor (EGFR) gene confer sensitivity to the tyrosine kinase inhibitors (TKIs)in patients with advanced nonsmall cell lung cancer (NSCLC). TKI treatment efficacy and EGFR mutation implications were evaluated in clinically selected advanced NSCLC patients treated with TKIs in routine clinical practice. Materials and Methods: A retrospective chart review for clinicopathological characteristics and mutation status (EGFR, KRAS) analysis of 40 consecutive patients treated with TKIs between 2005 and 2010 was performed. Statistical Analysis Used: PFS and OS were estimated by the Kaplan-Meier method, the log-rank test was used to test for differences. The strength of the associations between the EGFR mutation status and clinicopathological characteristics were tested with the Mann-Whitney U-test or the Kruskal-Wallis H-test.Results: The prevalence of EGFR mutations was 45% with a predominance of deletion mutations in exon 19 (55.5%). Significant correlations between gender, histology, and EGFR mutations were observed. Median progression-free survival (mPFS) for the entiregroup of patients was 8.7 months and median overall survival (mOS) was not yet reached. Patients with EGFR mutant tumors derived significantly higher benefit from TKI therapy compared to patients with mutation-negative disease; with mPFS of 22.0 vs. 3.2 months(HR: 3.9, 95% CI 1.569.89) and with a trend towards better OS (probability of survival at 12 months 82.0 vs. 63.0%, P = 0.080). Conclusion: We demonstrated that screening for EGFR mutations is reliable in a routine clinical setting and might allow for a better selection of NSCLC patients for anti-EGFR TKI therapy.
COBISS.SI-ID: 1603963
Background: This was a prospective phase II study of cisplatin and bortezomib (CB) in the first line treatment of malignant pleural mesothelioma (MPM) with validation of progression free survival rate at 18 weeks (PFSR-18)1 as primaryend-point. Methods: Chemotherapy-naïve patients with histologically proven MPM and performance status (PS) 0/1, were treated with cisplatin 75 mg/m2 on day 1 and bortezomib 1.3 mg/m2 on days 1, 4, 8, 11 every 3 weeks. The primary end-point validation utilised the landmark method. Results: Between 2007 and 2010 82 patients were entered. PFSR-18 was 53% (80% confidence intervals, CIs, 42-64%). The overall survival (OS) was 13.5 months (95% CI 10.5-15) with 56% (95% CI 44-66%) alive at 1 year. The median PFS was 5.1 months (95% CI 3.3-6.5) and the response rate was 28.4% (95% CI 18.9-39.5%). The most frequent grade 3-4 toxicities were hyponatremia (46%), hypokalaemia (17%), fatigue (12.2%), thrombocytopenia (11%), neutropenia (9.7%) and neurotoxicity (motor, sensory, other: 1.2%, 8.5%, 2.4%). There were two toxic deaths (32 and 74 days) due to acute pneumonitis and cardiac arrest. End-point validation showed that patients with no progression/progression at 18 weeks had median OS of 16.9/11.9 months, respectively. Hazard ratio was 0.46 (CI 0.32-0.67), logrank test and C-index were 0.007 and 0.60. Conclusion: The 50% PFSR-18 for CB was contained within the 80% CI for (42-64%). Therefore the null hypothesis could not be rejected. Accordingly this combination does not warrant further investigation. PFSR-18 was confirmed as a strong predictor of survival.
COBISS.SI-ID: 36913157
Lung cancer is the most lethal form of cancer in the world and despite significant therapeutic improvements that have been made, its survival rate still remains low. The latter is mainly due to the acquisition of resistance to systemic treatment regimens which, in turn, may be due to the presence of cancer stem cells (CSCs) within the primary tumors. CSCs constitute a subpopulation of cells that are highly tumorigenic and that exhibit biological properties similar to those of normal tissue stem cells, including an unlimited self-renewal capacity, an extensive proliferative capacity and a capacity to generate differentiated progeny. A better understanding of the signaling pathways that regulate lung CSC maintenance, proliferation, and tumorigenicity could thus lead to the design of improved approaches to lung cancer treatment. Aim In this review we will discuss the current knowledge on lung CSCs, their biological properties and their putative clinical relevance. By employing currently available data, we will evaluate the prognostic value of several lung CSC markers. In addition, we will discuss the release of CSCs from tumor tissue into the blood circulation via epithelial-mesenchymal transition (EMT) as an important step towards acquiring a metastatic phenotype. Finally, we will provide an outlook into novel CSC-targeting approaches for achieving less invasive diagnostic procedures and improving long-term therapeutic options. Conclusion Lung CSC research has gained considerable momentum to both basic and clinical applications, both aiming to identify a reliable panel of markers for lung CSCs and to clarify their function, with the final goal to develop a CSC-targeted therapy that will result in the complete elimination of CSCs for achieving significantly better long-time survival of lung cancer patients.
COBISS.SI-ID: 2869071