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<p><b>Objective</b>Exposure to halogens, such as chlorine or bromine, results in environmental and occupational hazard to the lung and other organs. Chlorine is highly toxic by inhalation, leading to dyspnea, hypoxemia, airway obstruction, pneumonitis, pulmonary edema, and acute respiratory distress syndrome (ARDS). Although bromine is less reactive and oxidative than chlorine, inhalation also results in bronchospasm, airway hyperresponsiveness, ARDS, and even death. Both halogens have been shown to damage the systemic circulation and result in cardiac injury as well. There is no specific antidote for these injuries since the mechanisms are largely unknown.</p><p><b>Data Sources</b>This review was based on articles published in PubMed databases up to January, 2018, with the following keywords: "chlorine," "bromine," "lung injury," and "ARDS."</p><p><b>Study Selection</b>The original articles and reviews including the topics were the primary references.</p><p><b>Results</b>Based on animal studies, it is found that inhaled chlorine will form chlorine-derived oxidative products that mediate postexposure toxicity; thus, potential treatments will target the oxidative stress and inflammation induced by chlorine. Antioxidants, cAMP-elevating agents, anti-inflammatory agents, nitric oxide-modulating agents, and high-molecular-weight hyaluronan have shown promising effects in treating acute chlorine injury. Elevated free heme level is involved in acute lung injury caused by bromine inhalation. Hemopexin, a heme-scavenging protein, when administered postexposure, decreases lung injury and improves survival.</p><p><b>Conclusions</b>At present, there is an urgent need for additional research to develop specific therapies that target the basic mechanisms by which halogens damage the lungs and systemic organs.</p>
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Animais , Humanos , Lesão Pulmonar Aguda , Cloro , Toxicidade , Halogênios , Toxicidade , Pulmão , Patologia , Síndrome do Desconforto Respiratório , Tratamento FarmacológicoRESUMO
Objective: To investigate the relationship between 5-FU (5-fluorouracil) dose (based on body surface area or not) and its plasma concentration and the overall survival of patients with advanced colorectal cancer receiving 5-FU-based chemotherapy regimens as standard first- and second-line treatment. Methods: One hundred and ninety-two patients with advanced colorectal cancer received 5-FU-based chemotherapy regimens of FOLFOX (5-FU, calcium folinate and oxaliplatin) and FOLFIRI (5-FU, calcium folinate and irinotecan ) as first-line and second-line chemotherapy, respectively or in a reverse sequence. Plasma concentration of 5-FU at steady state was examined when the dose of 5-FU was adjusted according to the toxicity in each patient. Results: The plasma concentration of 5-FU was not associated with the dose of continuous infusion of 5-FU (r = 0.066, P = 0.146), and also not associated with the dose of infusional 5-FU based on body surface area (r = 0.056, P = 0.217). Median overall survival was 31.4 months for patients with high plasma concentration of 5-FU (> 30 μg/L) versus 14.5 months for patients with low plasma concentration of 5-FU (< 30 μg/L) (P = 0.001). The adverse effects including grades 3-4 neutropenia and hand foot syndrome were more frequent in patients with high plasma concentration of 5-FU. Conclusion: The monitoring of plasma concentration of 5-FU may be a basis for dose adjustment of 5-FU in safe and effective range for patients with advanced colorectal cancer. Copyright © 2013 by TUMOR.
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Objective: To assess the value of plasma concentration of 5-FU (5-fluorouracil) predicting the efficacy and safety in patients with advanced gastric cancer receiving capecitabine plus cisplatin as first-line chemotherapy. Methods: The clinical data from 113 advanced gastric cancer patients receiving capecitabine plus cisplatin in Shanghai First People's Hospital from July 2007 to December 2010 were retrospectively collected. The plasma concentration of 5-FU was examined at each cycle of chemotherapy. The relationships between plasma concentration of 5-FU and the OS (overall survival), PFS (progression-free survival) and RR (response rate) were determined by statistical analysis. Results: The mean plasma concentration of 5-FU was 25.8 μg/L. The patients were divided into group A (plasma concentration of 5-FU > 25 μg/L, n = 59) and group B (plasma concentration of 5-FU < 25 μg/L, n = 54). The median OS time of group A and group B were 14.4 and 9.6 months, respectively (hazard ratio = 0.36, P = 0.000). The median PFS time of group A and group B were 8.0 and 4.9 months, respectively (hazard ratio = 0.37, P = 0.000). The RR of group A and group B were 55.9% and 33.3%, respectively (P = 0.023). All toxicities occurred more frequently in group A than in group B. The grade III/IV mocositis and hand-foot syndrome were significantly increased in group A as compared with group B. Conclusion: For advanced gastric cancer, high plasma concentration of 5-FU might predict efficacy and toxicities of capecitabine plus cisplatin. Copyright © 2013 by TUMOR.
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Objective: To evaluate the prognostic priority of the 7th edition AJCC (American Joint Committee on Cancer) TNM staging system for gastric carcinoma compared with the 6th edition in Chinese population. Methods: A total of 918 patients with gastric carcinoma from a single institution between January 2003 and December 2008 in China were staged using the 6th edition and the 7th edition AJCC TNM staging systems. The univariate and multivariate analyses were applied to evaluate the value of the two staging systems in prognostic prediction for gastric carcinoma. The AIC (Akaike's Information Criterion) was used to determine which is better between the two staging systems. Results: Significant differences in overall survival were observed according to the T, N and M substages using the 7th edition AJCC TNM staging system. The Kaplan-Meier survival curves showed a good discriminatory ability among stages I through IV in both the 6th and 7th edition staging systems (P = 0.000). There were similar survival curves between substages IA and IB (P = 0.643), IB and IIA (P = 0.267), IIB and IIIA (P = 0.534), IIIA and IIIB (P = 0.124), and IIIB and IIIC (P = 0.174) when the patients were classified into eight substages according to the 7th edition AJCC TNM staging system. The AIC value of the 7th edition staging system was smaller than the 6th edition staging system. Conclusion: The 7th edition AJCC TNM staging system is superior to the 6th edition staging system. But the advantage of the new 7th edition staging system is very limited and it presents some deficiencies. Copyright © 2012 by TUMOR.
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<p><b>OBJECTIVE</b>To investigate the relationship between serum concentration of fluorouracil and therapeutic efficacy as well as adverse reactions in patients with unresectable locally advanced or measurable metastatic colorectal cancer, and to analyze its role in further improving therapeutic efficacy and reducing adverse reactions of fluorouracil-based chemotherapy.</p><p><b>METHODS</b>Eighty-six patients were randomly assigned into three groups according to the average plasma concentration of fluorouracil after three cycles of chemotherapy with the initial regimen of two weeks FOLFOX-4 (oxaliplatin + leucovorin + fluorouracil) or FOLFIRI (irinotecan + leucovorin + fluorouracil): group 1 (plasma concentration of fluorouracil < 25 ng/ml), group 2 (25 - 35 ng/ml) and group 3 (> 35 ng/ml). The blood samples were taken at 12 h after continuous infusion of fluorouracil in each cycle and the plasma concentration of fluorouracil was detected by high performance liquid chromatography (HPLC) (about 5 am ± 1 h). The relationship between the drug plasma concentration, therapeutic efficacy and adverse reactions in different fluorouracil plasma concentration arms was analyzed retrospectively.</p><p><b>RESULTS</b>The average plasma concentrations of fluorouracil of the three groups were (23.48 ± 1.95) ng/ml, (31.47 ± 2.33) ng/ml and (39.89 ± 3.87) ng/ml, respectively (P < 0.01). As for therapeutic efficacy, the median OS of the groups 2 and 3 were 18.0 and 17.5 months, significantly higher than that in the group 1 (13.0 months, P < 0.01). The PFS were 4.5, 7.5 and 8.0 months, respectively (P < 0.01). In terms of adverse reactions, the incidences of bone marrow suppression, mucositis and diarrhea in the group 3 were significantly higher than that in the first two groups (P = 0.02, P = 0.04 and P = 0.02).</p><p><b>CONCLUSIONS</b>The patients with local advanced and metastatic colorectal cancer, receiving fluorouracil-based chemotherapy, and with an average plasma concentration of fluorouracil between 25 - 35 mg/L have a better prognosis, and lower incidence of adverse reactions such as bone marrow suppression, mucositis and diarrhea.</p>