Assuntos
Estesioneuroblastoma Olfatório/tratamento farmacológico , Indazóis/uso terapêutico , Cavidade Nasal , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Nasais/tratamento farmacológico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Idoso , Estesioneuroblastoma Olfatório/genética , Estesioneuroblastoma Olfatório/secundário , Feminino , Fumarato Hidratase/genética , Humanos , Mutação , Neoplasias Nasais/genética , Neoplasias Nasais/patologia , Indução de Remissão , Retratamento , Fatores de TempoRESUMO
INTRODUCTION: Therapeutic plasma 5-fluorouracil (5-FU) levels are achieved in only 20% to 30% of patients with the current practice of administering 5-FU doses based on body surface area (BSA). Alternatively, 5-FU doses can be adjusted based on 5-FU pharmacokinetic (PK) monitoring. Although benefits of PK monitoring of 5-FU in metastatic colorectal cancer (CRC) have been reported, its utility among patients with early stage disease has not been reported. PATIENTS AND METHODS: We retrospectively examined the effect of 5-FU PK monitoring in 84 CRC patients (49 stage IV and 35 stage II/III) receiving mFOLFOX6 (modifiedFOLFOX6; modified 5-fluorouracil, leucovorin, oxaliplatin protocol) or mFOLFIRI (modified 5-fluorouracil, leucovorin, irinotecan protocol). Forty-six of the 84 patients received 5-FU doses based on BSA and 38 received doses that were adjusted with PK monitoring. 5-FU plasma levels were measured using a nanoparticle immunoassay method. RESULTS: 5-fluorouracil PK monitoring significantly improved disease-free survival in stage II/III patients (P = .0429). There was also a trend towards improved progression-free survival among stage IV patients who had their 5-FU levels PK-monitored (P = .16). Moreover, 5-FU PK monitoring significantly reduced (P = .0437) and delayed (P = .0144) adverse effects in stage II/III patients. Toxicity occurred after the second 5-FU dose in the BSA group and after the sixth to seventh dose in the PK monitoring group. In stage IV patients, the onset of toxicities was also delayed with PK monitoring (P = .0605). CONCLUSION: We provide evidence that PK monitoring of 5-FU is potentially beneficial for late stage and early stage CRC. These results contribute to the growing body of evidence regarding patient benefit when treatment decisions are based on the individual patient characteristics, in this case, a patients' 5-FU levels.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/administração & dosagem , Camptotecina/farmacocinética , Camptotecina/uso terapêutico , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Fluoruracila/administração & dosagem , Fluoruracila/farmacocinética , Fluoruracila/uso terapêutico , Humanos , Leucovorina/administração & dosagem , Leucovorina/farmacocinética , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/farmacocinética , Compostos Organoplatínicos/uso terapêutico , Medicina de Precisão , Estudos RetrospectivosRESUMO
OBJECTIVE: To model the relationship of an area-based measure of a breast cancer screening and geographic area deprivation on the incidence of later stage breast cancer (LSBC) across a diverse region of Appalachia. DATA SOURCE: Central cancer registry data (2006-2008) from three Appalachian states were linked to Medicare claims and census data. STUDY DESIGN: Exploratory spatial analysis preceded the statistical model based on negative binomial regression to model predictors and effect modification by geographic subregions. PRINCIPAL FINDINGS: Exploratory spatial analysis revealed geographically varying effects of area deprivation and screening on LSBC. In the negative binomial regression model, predictors of LSBC included receipt of screening, area deprivation, supply of mammography centers, and female population aged>75 years. The most deprived counties had a 3.31 times greater rate of LSBC compared to the least deprived. Effect of screening on LSBC was significantly stronger in northern Appalachia than elsewhere in the study region, found mostly for high-population counties. CONCLUSIONS: Breast cancer screening and area deprivation are strongly associated with disparity in LBSC in Appalachia. The presence of geographically varying predictors of later stage tumors in Appalachia suggests the importance of place-based health care access and risk.