First reported double drug-drug interaction in a cancer renal patient under everolimus treatment: therapeutic drug monitoring and review of literature.

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.

Measurement of total and free docetaxel concentration in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry.

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 808.3→527.0 (quantifier) and 808.3→509.0 (qualifier); and 854.3→569.0 (quantifier) and 854,3→509,0 (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.

[Evaluating colorectal cancer screening strategies (immunological test vs biochemical test) in Catalonia, Spain 2008-2010]. / Evaluación de dos estrategias de cribado de cáncer colorrectal: test inmunológico versus test bioquímico. Cataluña, 2008-2010.

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.