Background: Chemotherapies of solid tumors commonly include 5-fluorouracil (5-FU). With standard doses of 5-FU, substantial inter-patient variability has been observed in exposure levels and treatment response. Recently, improved outcomes in colorectal cancer patients due to pharmacokinetically guided 5-FU dosing were reported. We aimed at establishing a rapid and sensitive method for monitoring 5-FU plasma levels in cancer patients in our routine clinical practice. Methods: Performance of the Saladax My5-FU ™ immunoassay was evaluated on the Roche Cobas
Binary-system capillary electrophoresis (CE) with head-column field-amplified sample stacking permits determination of amiodarone and desethylamiodarone in 20-microL serum samples. The assay is characterized by a detection limit for both compounds of 80 nmol/L and by excellent linear response over the recommended therapeutic range for amiodarone (1.5-4 mumol/L). Intra- and interday reproducibilities (CVs) between 3% and 6% and run times of approximately 10 min are comparable with those for conventional HPLC. Besides excellent sensitivity, attractive features of the assay include low operating costs, high separation efficiency, rapid drug extraction, consumption of almost negligible amounts of organic solvents, and simple operation. If appropriate microvessels and liquid-handling facilities are available, the same assay can be performed with 2 microL of serum, and if the serum is not diluted but rather is concentrated during extraction, < 1 nmol/L of amiodarone can be detected.
(1) Background: High-dose chemotherapy (HDCT) before autologous stem cell transplantation (ASCT) in acute myeloid leukemia (AML) patients predominantly combines busulfan with cyclophosphamide or melphalan. Treosulfan compares favorably regarding lower inter-individual bioavailability and neurotoxicity, but so far, had not been studied before ASCT in AML. (2) Methods: This single-center study investigated AML patients undergoing ASCT in CR1 between November 2017 and September 2020. The first 16 patients received busulfan 16 mg/kg b.w. (days −5 to −2) and melphalan 140 mg/m2 (day −1) (BuMel). In a subsequent (TreoMel) cohort, 20 patients received treosulfan 14 g/m2 (days −4 to −2) and melphalan. Plasma concentrations of busulfan and treosulfan were determined by mass spectrometry. (3) Results: Neutrophil engraftment and platelet recovery were similar, and PFS and OS were comparable. In only the BuMel cohort, patients reported central nervous toxicities, including seizures (6%) and encephalopathy (12%). The mean AUC for busulfan was 1471.32 μM*min, and for treosulfan it was 836.79 mg/L*h, with ranges of 804.1–2082 μM*min and 454.2–1402 mg/L*h. The peak values for busulfan ranged between 880.19–1734 μg/L and for treosulfan between 194.3–489.25 mg/L. (4) Conclusions: TreoMel appears to be safe and effective for pre-ASCT treatment in AML patients. Due to considerable interindividual biovariability, pharmacologic monitoring may also be warranted for the use of treosulfan.
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