RESUMO
For the majority of cytotoxic drug preparations, such as bortezomib, the unit dose information is not available. In addition, there is a lack of information on the physicochemical stability of the pharmaceutical preparation after opening; this information is crucial for its administration to patients in successive visits, and the per-patient cost can be affected. The purpose of our proposed physicochemical stability study is to determine the shelf life of the reconstituted liquid product under refrigeration and clinical practice conditions. This evaluation was extended to both vials and ready-to-use syringes prefilled with the contents of the open vial. The stability test design includes the specified storage conditions and the critical physicochemical parameters of reconstituted injectable bortezomib. Furthermore, this approach includes the determination of impurities, the monitoring of the purity of the mean peak using a photodiode array, the control of the mass balance, the monitoring of subvisible particles using a laser diffraction analyser, and the setting of stability specifications. For the chemical stability study, the amount of bortezomib and its degradation products were determined using a stability-indicating HPLC method. The physical inspection of the samples was performed throughout the stability study, and their pH values were also monitored. Bortezomib (2.5 mg/mL) in 0.9% sodium chloride remained stable for 7 days when stored in both polypropylene syringes and vials at 5 ± 3 °C (refrigeration) and shielded from light. Additionally, it exhibits stability for 24 h under storage conditions simulating clinical use (20-30 °C and protected from light). The proposed protocol provides the stability in the vials once reconstituted and in prefilled refrigerated syringes; this protocol can be used to reduce waste and increase cost savings.
Assuntos
Antineoplásicos , Embalagem de Medicamentos , Humanos , Bortezomib , Polipropilenos/química , Estabilidade de Medicamentos , Seringas , Cromatografia Líquida de Alta Pressão , Soluções Farmacêuticas/químicaRESUMO
Limited literature is available for bevacizumab exposure-response relationship and there is not a concentration threshold associated with an optimal disease control. This prospective observational study in patients with metastatic colorectal cancer (mCRC) aims to evaluate, in a real-life setting, the relationship between bevacizumab through concentrations at steady state (Ctrough, SS) and disease control. Ctrough, SS were drawn, coinciding with the radiological evaluation of the response (progression or clinical benefit). Generalized estimating equations (GEE) analysis was performed. To test the association between Ctrough, SS in each patient with overall survival (OS) or progression-free survival (PFS), Cox proportional hazard models were developed. Data included 50 bevacizumab Ctrough, SS from 27 patients. The GEE model did not suggest any positive association between bevacizumab Ctrough, SS and clinical benefit (OR 0.99, 95% CI: 0.98-1.02, p = 0.863). The Cox regression showed association between higher median Ctrough, SS with better OS (HR 0.86, 95% CI: 0.73-1.01, p = 0.060), but not with PFS. We cannot confirm a relationship between bevacizumab Ctrough, SS and clinical benefit but this is the first real-world study trying to show a relationship between bevacizumab Ctrough, SS and disease control in mCRC. It was conducted in a small sample size which reduces the level of evidence. Further controlled randomized studies with a sufficient number of patients are required.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/secundário , Idoso , Inibidores da Angiogênese/uso terapêutico , Antineoplásicos Imunológicos/farmacocinética , Bevacizumab/farmacocinética , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Prospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: There is limited scientific evidence on the cetuximab exposure-response relationship and no concentration threshold has been associated with optimal disease control. The aims were to assess, in a real-life setting, the relationship between steady state cetuximab concentrations (Ctrough, SS) and disease control. METHOD: A prospective observational study in patients with metastatic colorectal cancer or head and neck cancer treated with cetuximab. Steady state trough concentrations were compared with the results of radiological assessment of response (progression or clinical benefit). Generalized estimating equations analysis was performed. To test the association between steady state concentrations and overall survival and progression-free survival, Cox proportional hazard models were developed. An optimal cut-off point was searched using the area under the receiver operating characteristic curve. RESULTS: A total of 30 steady state cetuximab concentrations from 16 patients were analysed. Median Ctrough, SS was 26.86 mg/L and there was marked inter- and intraindividual variability (standard deviation 32.4 mg/L and 16.9 mg/L, respectively). A positive association was found between cetuximab Ctrough, SS and clinical benefit (odds ratio 1.24, 95% confidence interval: 0.95-1.63, p = 0.113), although without reaching statistical significance. The area under the receiver operating characteristic curve (n = 30) had moderate discrimination power (0.71; 95% confidence interval 0.490.93), and the empirical optimal cutoff point was 19.12 mg/L. However, no association was observed between cetuximab Ctrough, SS and survival in metastatic colorectal cancer or neck cancer patients. CONCLUSIONS: We cannot confirm a relationship between cetuximab Ctrough, SS and disease control despite a positive association. This study was conducted with a small sample, which reduces the power analysis. Further controlled randomised studies with a sufficient number of patients are needed.
OBJETIVO: Evaluar, en condiciones de vida real, la relación entre las concentraciones valle en estado estacionario de cetuximab y el control de la enfermedad, así como buscar la relación entre estas concentraciones y la supervivencia. Además, estudiar si existe una concentración límite que se pueda asociar con la probabilidad de beneficio clínico.Método: Estudio observacional prospectivo llevado a cabo en pacientes con cáncer colorrectal metastásico o cáncer de cabeza y cuello en tratamiento con cetuximab. Se realizó un análisis de regresión de ecuaciones de estimación generalizadas para evaluar la asociación entre la concentración valle en estado estacionario de cetuximab y la respuesta al tratamiento (progresión o beneficio clínico). Mediante modelos de riesgos proporcionales de Cox, se evaluó la asociación entre la mediana de concentraciones valle en estado estacionario de cetuximab en cada paciente o la última medida con la supervivencia global y la supervivencia libre de progresión, en cada una de las patologías. Asimismo, se buscó un punto de corte óptimo a través del área bajo la curva de características operativas del receptor. RESULTADOS: Se analizaron 30 muestras de 16 pacientes. La concentración valle en estado estacionario mediana fue 26,86 mg/l y se encontró una gran variabilidad inter e intraindividual (desviación estándar de 32,4 y 16,9 mg/l, respectivamente). Se observó una asociación positiva entre la concentración valle en estado estacionario y el beneficio clínico (odds ratio 1,24; intervalo de confianza del 95%: 0,95-1,63; p = 0,113), aunque no alcanzó significación estadística debido a la baja potencia. El área bajo la curva de características operativas del receptor de las concentraciones (n = 30) tuvo una moderada capacidad discriminatoria (área bajo la curva de características operativas del receptor 0,710; intervalo de confianza del 95%: 0,49-0,93) y el punto de corte estimado fue de 19,12 mg/l. Sin embargo, no se observó relación entre la supervivencia y las concentraciones valle en estado estacionario en ninguna de las patologías. CONCLUSIONES: No se ha podido confirmar una relación entre exposición a cetuximab y eficacia, a pesar de encontrar una tendencia positiva en el control de la enfermedad con el aumento de la concentración valle en estado estacionario. El nivel de evidencia se vio reducido por la pequeña muestra de pacientes en cada grupo, por lo que se necesitan estudios aleatorizados y controlados, con un número suficiente de pacientes, para evaluar adecuadamente esta relación.
Assuntos
Neoplasias Colorretais , Neoplasias de Cabeça e Pescoço , Cetuximab/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Intervalo Livre de Progressão , Estudos ProspectivosRESUMO
PURPOSE: To compare the prevalence of potentially inappropriate medication (PIM) in the elderly according to the PRISCUS list, STOPP criteria, and Beers criteria. Secondary, to describe the differences using the three criteria focused on the inappropriate prescription of psychotropic drugs in the elderly. METHODS: A retrospective study was performed at Severo Ochoa University Hospital. The study included 365 patients, aged 80 years and older, living in Madrid, Spain. RESULTS: 93.42% of patients received at least one PIM during hospitalization. Using the PRISCUS list, this changed from 32.6 to 2.7% at discharge. Applying STOPP criteria lowered the percentage from 65.20 to 10.95%, and with Beers criteria from 80.27 to 10.13. Lower Barthel index at admission was associated with an increased relative risk for receiving at least one PIM (OR 1.79, 95% CI 1.15-2.80, p = 0.024) using PRISCUS list as a tool in conjunction with STOPP criteria (OR 1.44, 95% CI 0.89-2.33, p = 0.037). Polypharmacy at admission predicted the presence of PIMs with STOPP criteria (OR 1.74, 95% CI 1.07-2.84, p = 0.001). Regarding psychotropic medicines, 208 patients (56.98%) received at least one psychotropic medicine during hospitalization. A total of 26.30% of patients were treated with psychotropic medicines, detected by the PRISCUS list, and 53.97% and 29.85% with STOPP and Beers, respectively. CONCLUSIONS: Explicit criteria are a useful tool for identifying during hospitalization of the elderly patients. As indicated by the results, new research is needed to carry out an adaptation in our country that includes an evaluation of the strengths of the three tools to decrease PIMs and improve prescription in the elderly.
Assuntos
Hospitalização/estatística & dados numéricos , Prescrição Inadequada/estatística & dados numéricos , Polimedicação , Lista de Medicamentos Potencialmente Inapropriados/estatística & dados numéricos , Idoso de 80 Anos ou mais , Feminino , Hospitais Universitários , Humanos , Masculino , Estudos Retrospectivos , EspanhaRESUMO
The aim of this study was to compare the Memorial Sloan-Kettering Cancer Center (MSKCC) and the Cleveland Clinic Foundation (CCF) models of classification of aRCC patients. In addition, the model developed from the pivotal trial of temsirolimus and those proposed by Motzer et al. in 2004, Escudier et al., Heng et al., Choueiri et al. and Bamias et al. were examined. An observational, retrospective study of patients starting first-line systemic therapy was conducted between 2008 and 2011. The variables used to evaluate the classification models were median overall survival (mOS) and median progression-free survival (mPFS). The comparison of different classification models was performed by comparing the area under the ROC (Receiver Operating Characteristic) curve (AUC) for time-dependent variables proposed by Heagerty. Eighty-eight patients were included. When the different models were compared, it was found that although based on the mOS, the Escudier model had better short-term (1-year) prognostic value, followed by the Heng model; in the long term, the models that presented a higher prognosis capacity were the Hudes and CCF models, closely followed by the Heng model. In addition, the Heng model had a slightly higher predictive ability than the other models. Based on the results, and in line with the European society for medical oncology (ESMO) guidelines, it appears that the model of Heng could be the best model to classify patients with aRCC and combines good short- and long-term prognostics while possessing better predictive ability and a more equal distribution of patients.