ABSTRACT
Everolimus is an inhibitor of mammalian target of rapamycin (mTOR) used in both transplantation and cancer treatment (breast, renal and neuroendocrine). In transplantation, therapeutic drug monitoring (TDM) is recommended due to the potential drug-drug interactions with chronic medications, which can affect everolimus pharmacokinetics. In cancer treatment, everolimus is used at higher doses than in transplantation and without a systematic drug monitoring.We present a case report of a 72-year-old woman with epilepsy history to whom everolimus 10 mg QD was prescribed as third line of treatment for renal cell carcinoma (RCC). The potential drug interactions between everolimus and the patient's chronic medications, carbamazepine and phenytoin, are significant as both are known as strong inducers CYP3A4 metabolism, potentially leading to underexposure to everolimus.TDM of everolimus was recommended by the pharmacist. The literature suggests that a minimum plasma concentration (Cminss) of everolimus over 10 ng/ml is associated with better response to treatment and progression-free survival (PFS). The patient's everolimus dose had to be increased until 10 mg BID, and regular monitoring of everolimus levels showed an increase in Cminss from 3.7 ng/ml to 10.8 ng/ml.This case highlights the importance of checking for potential drug interactions and monitoring everolimus levels in patients on chronic medication, especially those with several inducers or inhibitors of CYP3A4 metabolism. TDM can help to ensure that patients are treated with their optimal dose, which can improve the effectiveness of the treatment or minimize the risk of toxicities.
Subject(s)
Everolimus , Kidney Neoplasms , Female , Humans , Aged , Everolimus/adverse effects , Drug Monitoring , Cytochrome P-450 CYP3A , Drug InteractionsABSTRACT
Docetaxel is a semi-synthetic taxane with cytotoxic anti-neoplastic activity and, currently used as anticancer agent in several types of cancer. Docetaxel is highly bound to plasma proteins, and this significantly determines its clearance and activity. Therefore, measurement of free docetaxel in plasma is pharmacologically important when pharmacokinetics is investigated. We developed and validated chromatographic methods by ultra-performance liquid chromatography-tandem mass spectrometry to measure total and free docetaxel concentration in human plasma. The final validated methods involved liquid-liquid extraction followed by dryness under nitrogen evaporation. To measure free docetaxel concentration, sample preparation was preceded by ultrafiltration. Chromatographic separation was achieved using an Acquity(®) UPLC(®) BEH™ (2.1×100 mm id, 1.7 µm) reverse-phase C18 column at a flow rate of 0.4 mL/min, using isocratic elution mode containing ammonium acetate/formic acid in water/methanol (30:70 v/v) as mobile phase. Docetaxel and its internal standard (paclitaxel) were detected by electrospray ionization mass spectrometry in positive ion multiple reaction monitoring mode using mass-to-charge (m/z) transitions of 808.3â527.0 (quantifier) and 808.3â509.0 (qualifier); and 854.3â569.0 (quantifier) and 854,3â509,0 (qualifier), respectively. The run time per sample was 3.5 min. The limits of quantification were 1,95 and 0.42 µg/L and linearity was observed between 1.95 and 1000 and 0.42-100 µg/L for total and free docetaxel, respectively. Coefficients of variation and absolute relative biases were less than 13.8% and 10.0%. Recovery values were greater than 79.4%. Evaluation of the matrix effect showed ion suppression and no carry-over was observed. The validated methods could be useful for both therapeutic drug monitoring and pharmacokinetic studies. They could be applied to daily clinical laboratory practice to measure the concentration of total and free docetaxel in plasma.
Subject(s)
Antineoplastic Agents/blood , Tandem Mass Spectrometry/methods , Taxoids/blood , Chromatography, High Pressure Liquid/methods , Docetaxel , Humans , Ultrafiltration/methodsABSTRACT
Fundamento: El objetivo del estudio fue evaluar el cambio de estrategia de cribado (test inmunológico cuantitativo) en un programa poblacional de detección precoz de cáncer colorrectal (CCR) en Cataluña. Métodos: La cuarta ronda del programa de cribado de CCR en Hospitalet de Llobregat se implementó en 2008-2010. Se ofreció un test bioquímico a 50.227 individuos y uno inmunológico cuantitativo a 12.707 individuos. Se analizaron diferencias en las dos estrategias de cribado respecto a variables de aceptabilidad (entre participación, abandonos y adherencia a la colonoscopia), de precisión diagnóstica (valor predictivo positivo y tasas de detección), de resultados (tamaño y localización de lesiones, estadio de los cánceres detectados) y de recursos (número necesario de colonoscopias e intervalo de tiempo entre el resultado positivo del test y la colonoscopia). Resultados: La participación en el cribado fue superior entre los individuos que utilizaron el test inmunológico (OR: 1,35; IC95%:1,27- 1,42). Las tasas de detección fueron superiores para el test inmunológico destacando la de adenomas de alto riesgo (26,7vs 3,0). El valor predictivo positivo para adenomas de alto riesgo fue del 45,0% y del 46,9% en el inmunológico y el guayaco, respectivamente. El número de colonoscopias necesarias para detectar un cáncer fue de casi el doble que en el guayaco (13,6 vs 7,4). Conclusiones: El test inmunológico es una buena estrategia de cribado especialmente sensible para la detección de adenomas de alto riesgo. Sin embargo, requiere realizar un gran número de colonoscopias y por ello se debe disponer de los recursos y medios necesarios (AU)
Background: The aim of this study was to evaluate the screening strategy (quantitative immunological test vs biochemical test) in a population- based screening program for colorectal cancer (CRC) in Catalonia. Methods: The fourth round of a screening program for CRC with a fecal occult blood test was implemented in Hospitalet de Llobregat during 2008-2010.Abiochemical test was offered to 50,227 individuals and a quantitative immunological test was offered to 12,707 individuals. We analysed differences according to the screening strategy in the following variables: acceptability of the target population (participation, dropouts, and adherence to colonoscopy), diagnostic accuracy (positive predictive value and detection rates), results (size and location of lesions, staging of CRC) and resources (number of colonoscopies needed and time interval between the positive test and colonoscopy). Results: Participation was higher among individuals who used the immunological test (OR: 1.35; CI95%:1.27-1.42). Detection rates for adenomas and cancer were also higher for the immunological test, hightlighting the detection rate for high-risk adenomas (26.7 vs. 3.0). The positive predictive value for high-risk adenomas was 45.0% and 46.9% in the immunological test and guaiac test, respectively. The number of colonoscopies needed to detect cancer with the immunological test was almost two-fold than those needed with the guaiac test (13.6 vs 7.4). Conclusions: The immunological test is a good screening strategy particularly sensitive for detecting high-risk adenomas. However, it is paramount to have enough resources to assure the quality of the CRC screening due to the large number of colonoscopies that would be required (AU)
Subject(s)
Humans , Male , Female , Middle Aged , Mass Screening/methods , Early Diagnosis , Clinical Chemistry Tests/methods , Colonoscopy , Outcome and Process Assessment, Health Care/organization & administration , Outcome and Process Assessment, Health Care , Immunologic Tests/methods , Immunologic Tests , Mass Screening/prevention & control , Mass Screening/statistics & numerical data , Clinical Chemistry Tests/statistics & numerical data , Clinical Chemistry Tests/trends , Clinical Chemistry Tests , Outcome and Process Assessment, Health Care/methods , Outcome and Process Assessment, Health Care/trends , Evaluation of Results of Preventive Actions/methods , Evaluation of Results of Preventive Actions/trends , Immunologic Tests/trendsABSTRACT
BACKGROUND: The aim of this study was to evaluate the screening strategy (quantitative immunological test vs biochemical test) in a population-based screening program for colorectal cancer (CRC) in Catalonia. METHODS: The fourth round of a screening program for CRC with a fecal occult blood test was implemented in Hospitalet de Llobregat during 2008-2010. A biochemical test was offered to 50,227 individuals and a quantitative immunological test was offered to 12,707 individuals. We analysed differences according to the screening strategy in the following variables: acceptability of the target population (participation, dropouts, and adherence to colonoscopy), diagnostic accuracy (positive predictive value and detection rates), results (size and location of lesions, staging of CRC) and resources (number of colonoscopies needed and time interval between the positive test and colonoscopy). RESULTS: Participation was higher among individuals who used the immunological test (OR: 1.35; CI95%:1.27-1.42). Detection rates for adenomas and cancer were also higher for the immunological test, hightlighting the detection rate for high-risk adenomas (26.7 vs. 3.0). The positive predictive value for high-risk adenomas was 45.0% and 46.9% in the immunological test and guaiac test, respectively. The number of colonoscopies needed to detect cancer with the immunological test was almost two-fold than those needed with the guaiac test (13.6 vs 7.4). CONCLUSIONS: The immunological test is a good screening strategy particularly sensitive for detecting high-risk adenomas. However, it is paramount to have enough resources to assure the quality of the CRC screening due to the large number of colonoscopies that would be required.
