The correlation between methods was excellent, and Passing-Bablok regression analysis detected no virtually difference in their results. Utilization of the CMIA-Architect assay to measure MTX concentrations would therefore not affect clinical decisions on MTX management, supporting its employment in routine MTX monitoring.

BackgroundEribulin is approved for use in pretreated metastatic breast cancer (MBC) patients after at least two chemotherapy regimens for advanced disease.PurposeTo assess the effectiveness and safety of eribulin in MBC.Material and methodsRetrospective observational study in patients treated with eribulin monotherapy from February 2014 to September 2015 in a tertiary hospital. Effectiveness was measured with OS and PFS. Safety was assessed by NCI-CTCAE criteria v.3.0. Data collected were: sex, age, immunohistochemistry, location and degree of metastasis, ECOG, prior lines of treatment, number of cycles of eribulin and adverse events. The information was obtained from Oncofarm program and digital Diraya history. Data analysis was performed using PASW Stadistic18 package.Results19 women were studied, median age 55 years (38–73), ECOG 0–2, RH+ (68.4%) and HER2+ (15.78%) receptors. All patients had metastases IIIb-IV grade in different locations: liver (63.15%), bone (57.9%), lung (26.3%), brain (10.52%) and nodal (10.52%). They previously received a median of 6 lines of treatment (3–9): anthracyclines (89.47%), capecitabine (84.2%), taxanes (78.9%) and vinorelbine (63%). Eribulin dose was 1.23 mg/m² on days 1 and 8, 21 day cycles intravenously. The average number of cycles administered was 4.75. Median OS was 2.5 months obtained with 95% CI (0.5 to 8.6) and PFS was 5.2 months with 95% CI (3.4 to 7). Eight patients continue on treatment today. Adverse effects observed were: asthenia grade II (n = 2), diarrhoea grade I (n = 1), constipation grade I (n = 1) and febrile neutropenia grade IV (n = 1).ConclusionOur results agree with those already published; a similar OS and a higher PFS than obtained in the pivotal trial. Also, minimal toxicity was observed. We conclude that eribulin monotherapy is an effective and safe drug for MBC used as the 5th or 6th line of treatment.References and/or AcknowledgementsEuropean Medicines Agency. Halaven EPAR Product Information. EMA/H/C/002213/2011No conflict of interest.

BackgroundIntrathecal administration of methotrexate (MTX) in the treatment of different neoplastic diseases to prevent relapses in the CNS and the need to keep MTX concentrations in CSF during infusion of MTX requires study of the pharmacokinetics of MTX at this level. It is therefore necessary to measure concentrations of MTX in CSF.PurposeTo evaluate the validity (selectivity, accuracy and precision) of MTX measurements in CSF using a chemiluminescence assay for determination of MTX in plasma and to discard the matrix effect which might occur when measuring MTX in CSF.Material and methodsDifferent concentrations of MTX were tested in different types of samples to evaluate the selectivity and discard the matrix effect. To the studied matrix (CSF) were added increasing and known amounts of plasma with MTX (addition standard) and the results were correlated with the regression equation of the data obtained in both matrices. Accuracy was obtained by comparing the results of both matrices and obtaining the relative error. Due to the limitation of the small volume of CSF obtained in each extraction we were unable to perform different analyses on the same sample of CSF. 10 measurements on the same CSF sample containing a known quantity of MTX (obtained in our own test control) to evaluate precision were performed.ResultsFactor analysis of standard additions gave the regression line X=0.00233+1.0105Y. The correlation coefficient was r = 0.99 and the relative error was -2.3%. The series of 10 repetitions of CSF with a known concentration (436 μM) gave an average value of 445.44 μM (424–464 μM), with SD of 12.5 and a variation coefficient of 2.8%.ConclusionThe good selectivity, accuracy and precision of the CFS analysis by CMIA (Architect) gave reliable data on concentrations of MTX in CSF, highlighting the absence of the matrix effect.No conflict of interest.

BackgroundThe use of intrathecal (IT) methotrexate (MTX) in combination with systemic high dose MTX (HDMTX) is an established procedure for CNS prophylaxis in patients with acute lymphoblastic leukaemia (ALL), but the evidence for the necessity of this combination is not conclusive. An MTX concentration of 1 μM is assumed to be the lowest concentration for an antileukaemic effect.PurposeTo determine the rate of sufficient CSF MTX concentrations (1 μM) in paediatric patients with ALL who received HDMTX, to evaluate the suitability of IT MTX and to correlate MTX plasma and CSF concentrations.Material and methodsA retrospective observational study was conducted between April 2015 and September 2016. We included children up to 18 years with ALL who received 5000 mg/m² over 24 hours in accordance with LAL-SEHOP-PETHEMA-2013 protocols. CSF samples were obtained 18 hours (16–20 hours) after starting the HDMTX infusion and immediately before IT administration of MTX. Plasma samples were obtained at 2, 12, 23, 36, 42 and 60 hours after the start of infusion. CFS samples and plasma MTX at 12 hours were correlated by Spearman’s correlation. MTX was measured by architect chemiluminescence immunoassay.1 ResultsWe included 12 children, aged 2–16 years (7±3.6) who received 36 cycles of MTX. Patients received 5000 mg/m² over 24 hours; one child received 3000 mg/m² was included. MTX plasma levels at 12 hours and CSF concentrations were highly variable, ranging from 48.8 to 179.0 μM (median 72.2μM) and from 0.85 to 2.9 μM (median 1.4 μM), respectively. An MTX concentration above 1μM was found in 33 of 36 CSF samples (91.7%). The patient who received 3000 mg/m² (2 cycles) showed a lower CSF MTX concentration (0.83 and 1.08μM), corresponding to a lower plasma MTX concentration (54.37 and 60.88 μM). The correlation between plasma levels at 12 hours and CSF MTX concentrations was moderate–high (Spearman rank order correlation, r=0.71; p<0.01).ConclusionA potentially antileukaemic MTX concentration of 1 μM was obtained in CSF during the majority of MTX infusions (5000 mg/m2 over 24 hours).References and/or acknowledgements1. Montejano-Hervás P, et al. PKP-034. Determination of methotrexate in CSF by chemiluminescence using the architect. Eur J Hosp Pharm2016;23:A193–4.No conflict of interest

BackgroundIn the current treatment of Non-Hodgkin’s lymphomas (NHLs) with high-dose methotrexate, the dose is calculated according to different protocols, regardless of patients’ pharmacokinetic variability.PurposeTo evaluate the variability of exposure to methotrexate in adult patients with NHL who received high-dose methotrexate (>1,000 mg/m²) in order to justify the need to individualise the dose and optimise the treatment.Material and methodsRetrospective observational study, between October 2007 and June 2014. We included 43 adult patients (27–77 years old) with NHLs who received 96 cycles of methotrexate. Patients were classified into two groups, patients who received 1,000 mg/m² over 24 h in accordance with the HYPERCYVAD protocol (group I) and those who received 1,500 mg/m² infused over 24 h, following the BURKIMAB-08 protocol (group II). Methotrexate was measured by a fluorescence polarisation immunoassay (TDx/FLx System) in plasma samples obtained at 2, 12, 23, 36, 42 and 60 h after the start of infusion. Methotrexate pharmacokinetics parameters were estimated by Nonlinear Least Squares Regression (software Abbott PKs). The target range of exposure was defined as ±20% of the average AUC value, considering the extreme values positioned outside ±40%.ResultsIn group I, the AUC was 471.05 ± 188.59 μM h (235.29–1,231.34), 52.18% of the patients showed values within the pre-specified target (376.84–565.26), and 21.74% showed extreme values (>659.47 and <282.63). In group II, the AUC was 560.77 ± 194.63 μM h (308.53–1,414.62); 58% of patients showed values within the pre-specified target (448.62–672.93), and 16% showed extreme values (>785.08 and <336.46). The variability of the clearance in these patients (90.04 ± 30.59 ml/min/m²) would explain these results.ConclusionThe variability of exposure to methotrexate (37.99%) justifies the need to individualise dosage to optimise treatment. This could prevent an extreme risk of inefficacy or toxicity in the 18.75% of patients who are outside the pre-specified target range.References and/or acknowledgementsNo conflict of interest.