Vincristine (VCR) is an important drug used in the treatment of acute lymphoblastic leukemia (ALL). VCR-induced neurotoxicity can manifest as peripheral neuropathy, constipation, or paralytic ileus. While there are some case reports describing VCR-induced paralytic ileus (VIPI) in pediatric ALL, there are fewer publication on adult ALL patients. Therefore, we retrospectively investigated VIPI during induction therapy of treatment protocols for ALL in 19 adult patients. The incidence of VIPI was 32%. VIPI was significantly increased in patients receiving concomitant itraconazole (ITCZ) (p = 0.04). We recommend avoidance of the combination of VCR and ITCZ.
5 April 2022 in Journal of Chromatographic Science
Venetoclax is an oral B-cell lymphoma-2 protein inhibitor. It is a key drug for the treatment of chronic lymphocytic leukemia and acute myeloid leukemia. However, venetoclax is administered at a fixed dose, irrespective of body surface area or weight. Furthermore, the plasma concentration of venetoclax varies widely between individuals and is influenced by diet. Therefore, individualized dosing using therapeutic drug monitoring (TDM) may help to optimize treatment in clinical practice. In this study, we aimed to develop a simple method to determine venetoclax concentrations in plasma. The analysis required the extraction of a 50-μL plasma sample and precipitation of proteins using acetonitrile extraction. Venetoclax and the internal standard (12.5-μg/mL ibrutinib) were separated by high-performance liquid chromatography (HPLC). The calibration curve was linear over the plasma venetoclax concentration range 0.25–10 μg/mL with a coefficient of determination (r2) of 0.9999. The coefficients of intra-day and inter-day validation were 0.8–4.1% and 1.3–3.3%, respectively. The assay accuracy was −2.8 to 1.6%, and the recovery was >97.2%. These results demonstrate a very simple, novel and sensitive HPLC-UV-based method for determining the concentration of plasma venetoclax, and confirm its applicability to the TDM of venetoclax in a clinical setting.
Gastrointestinal cancer and its treatment using fluorouracil-based anticancer agents arc risk factors for thiamine deficiency (TD). Therefore. we aimed to determine the prevalence of TD among elderly patients with gastrointestinal cancer undergoing chemotherapy. We retrospectively reviewed the medical records of 12 elderly patients with gastrointestinal cancers who underwent chemotherapy. Median serum thiamine level was 22.5 ng/mL (range, 17 - 42 ng/mL). Four patients (33.3%) exhibited TD (< 20 ng/mL). We found that the prevalence of TD among elderly patients with gastrointestinal cancer undergoing chemotherapy was high. For these patients, careful monitoring of thiamine levels is warranted because TD may not produce overt clinical symptoms.