Search

PURPOSE: Taxane-induced peripheral neuropathy (TIPN) is a dose-limiting toxicity of paclitaxel in patients with cancer. TIPN prediction is challenging although patients with higher systemic paclitaxel exposure have higher TIPN risk. This study aimed to identify protein predictors of TIPN and paclitaxel pharmacokinetics (PK). METHODS: This is a retrospective analysis of a prospective study of females with early-stage breast cancer receiving weekly paclitaxel. TIPN was assessed using the sensory subscale of the European Organisation for Research and Treatment of Cancer QLQ-Chemotherapy-Induced Peripheral Neuropathy (CIPN)20 (CIPN8). A blood sample was collected within 10 minutes before the end of the first paclitaxel infusion to measure plasma proteins using liquid chromatography-mass spectrometry and to estimate maximum systemic paclitaxel concentration (C max). A second sample was collected approximately 24 hours after the first infusion to estimate paclitaxel time above threshold (T c >0.05). Linear mixed-effect and regression models were used to identify proteins predictive of TIPN and paclitaxel PK parameters, respectively, using a Bonferroni-adjusted α =.0006. RESULTS: Data from 36 participants were included in the analysis testing associations of 83 proteins with TIPN or PK. Higher levels of complement C3 were associated with more severe TIPN trajectories (P =.0002). No proteins were associated with either C max or T c >0.05 (all P >.0006). CONCLUSION: Complement C3 concentration at the end of initial paclitaxel infusion may be useful for identifying patients with breast cancer and potentially other tumor types who could benefit from TIPN prevention strategies to improve long-term treatment outcomes. [ABSTRACT FROM AUTHOR]

Study Objective: Neonatal opioid withdrawal syndrome (NOWS) is a condition that often occurs in neonates born to mothers who received methadone treatment for opioid use disorder during pregnancy. Early identification and treatment of infants at risk of NOWS may improve clinical outcomes. The purpose of this study was to evaluate whether maternal and umbilical cord plasma concentrations of methadone and its metabolite, 2‐ethylidene‐1,5‐dimethyl‐3,3‐diphenylpyrrolidine (EDDP), could predict the need for NOWS treatment. Design: Single‐center prospective study. Setting: University of Michigan Neonatal Intensive Care Unit. Patients: The study included 11 opioid‐dependent mother–infant dyads, where the mothers were treated with methadone at 34 weeks' gestation or later. Intervention: Maternal and cord blood samples were collected from the study participants. Measurements and Main Results: Maternal and cord plasma concentrations of methadone and EDDP were determined. Six out of the 11 infants required treatment for NOWS. Maternal methadone plasma concentrations were comparable between infants requiring and not requiring NOWS treatment (329.1 ± 229.7 ng/mL vs. 413.2 ± 329.8 ng/mL). However, the average cord plasma methadone concentration in infants who did not require NOWS treatment was 2.9‐fold higher than in those who required the treatment (120.0 ± 88.6 ng/mL vs. 40.9 ± 24.4 ng/mL), although the difference was not statistically significant. The ratios of maternal‐to‐cord methadone plasma concentrations were significantly higher in patients who required treatment for NOWS compared with those who did not (7.7 ± 1.9 vs. 3.5 ± 1.6, p = 0.003). Maternal and cord plasma EDDP concentrations and the maternal‐to‐cord plasma EDDP concentration ratios did not differ between patients who required and did not require treatment for NOWS. Conclusions: The results suggest that methadone permeability across the blood–placental barrier may affect in utero exposure to methadone, and the maternal‐to‐cord methadone plasma concentration ratio could be a potential biomarker for predicting the need for NOWS treatment. [ABSTRACT FROM AUTHOR]