Subject(s)
Aortic Aneurysm , Aortic Valve Insufficiency , Heart Valve Prosthesis Implantation , Aorta , Aortic Valve , Humans , Quality of LifeABSTRACT
BACKGROUND: The combination of bevacizumab with fluorouracil-based chemotherapy is a standard first-line treatment option in metastatic colorectal cancer (mCRC). We studied the efficacy of continuing or reintroducing bevacizumab in combination with second-line chemotherapy after progression to bevacizumab-based first-line therapy. PATIENTS AND METHODS: In this phase III study, patients with mCRC treated with fluoropyrimidine-based first-line chemotherapy plus bevacizumab were randomized to receive in second-line mFOLFOX-6 or FOLFIRI (depending on first-line regimen) with or without bevacizumab. The primary end point was progression-free survival. To detect a hazard ratio (HR) for progression of 0.70 with an α and ß error of 0.05 and 0.20, respectively, 262 patients were required. RESULTS: In consideration of the results of the ML18147 trial, the study was prematurely stopped. Between April 2008 and May 2012, a total of 185 patients were randomized. Bevacizumab-free interval was longer than 3 months in 43% of patients in chemotherapy alone arm and in 50% of patients in the bevacizumab arm. At a median follow-up of 45.3 months, the median progression-free survival was 5.0 months in the chemotherapy group and 6.8 months in the bevacizumab group [adjusted HR = 0.70; 95% confidence interval (CI) 0.52-0.95; stratified log-rank P = 0.010]. Subgroup analyses showed a consistent benefit in all subgroups analyzed and in particular in patients who had continued or reintroduced bevacizumab. An improved overall survival was also observed in the bevacizumab arm (adjusted HR = 0.77; 95% CI 0.56-1.06; stratified log-rank P = 0.043). Responses (RECIST 1.0) were similar in the chemotherapy and bevacizumab groups (17% and 21%; P = 0.573). Toxicity profile was consistent with previously reported data. CONCLUSIONS: This study demonstrates that the continuation or the reintroduction of bevacizumab with second-line chemotherapy beyond first progression improves the outcome and supports the use of this strategy in the treatment of mCRC. ClinicalTrials.gov number: NCT00720512.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Liver Neoplasms/drug therapy , Adult , Aged , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Disease Progression , Female , Follow-Up Studies , Humans , Liver Neoplasms/mortality , Liver Neoplasms/secondary , Male , Middle Aged , Neoplasm Staging , Prognosis , Prospective Studies , Retreatment , Survival RateABSTRACT
The authors studied prevalence of atherosclerosis, serum levels of lipids and homocysteine in coal miners suffering from pulmonary dust diseases. More marked hyperlipidemia and hyperhomocysteinemia are associated with combination of atherosclerosis and pulmonary dust diseases. Respiratory failure as a complication of pulmonary dust diseases promotes hyperlipidemia.
Subject(s)
Atherosclerosis/epidemiology , Dust , Hyperlipidemias/blood , Lung Diseases/blood , Lung Diseases/epidemiology , Occupational Diseases/epidemiology , Dyslipidemias/blood , Dyslipidemias/epidemiology , Female , Humans , Hyperhomocysteinemia/blood , Hyperhomocysteinemia/epidemiology , Hyperlipidemias/epidemiology , Male , Occupational Diseases/prevention & controlABSTRACT
The article deals with influence of coal rock dust on biochemical and immunologic serum parameters in experiment. Findings are that 3-week impact of coal rock dust (22 mg/m3) causes stress reaction and metabolism activation. Double increase of the duration and the concentration induces hypoxia component, immune deficiency elements and inflammation start.
