Speaker
Description
Background:
Paclitaxel (PTX) frequently causes dose-limiting toxicities (DLTs), notably chemotherapy-induced peripheral neuropathy and neutropenia, leading to reduced relative dose intensity (RDI). Body-surface-area dosing overlooks inter-individual variation in pharmacokinetics (PK), body composition, and physical activity (PA), potentially resulting in under- or overdosing, increased DLT risk, and reduced RDI, impacting the prognostic outcome.
Objective:
To explore whether favorable body composition and higher PA are associated with reduced PTX-related toxicities, and whether these associations are mediated by individual differences in PTX-PK, using data from the 20 participants of the PABTOX observational cohort.
Methods:
Women with stage I–IV breast cancer receiving weekly PTX (80 mg/m²; 12 cycles) are assessed at baseline (T0), cycle 3 (T1), cycle 6 (T2), cycle 9 (T3), and cycle 12 (T4). PK sampling occurs at T0, T1, T2, T3 and T4 at two timepoints (post-infusion ~10 min; 16–26 h) to determine PTX blood concentrations and half-life (Cmax and time > 0.05 µmol/L). Body composition is analyzed using dual-energy X-ray absorptiometry and bioelectrical impedance analysis at T0, T2, T3, and T4. PA is assessed by 7-day accelerometry and a validated questionnaire at T0, T2, T3 and T4. DLTs are graded each cycle (using the CTCAE v5.0).
Results:
Ongoing analyses will report PTX exposure distributions, and associations between skeletal muscle mass and adipose tissue, PA, PK parameters, and DLT occurence.
Conclusion:
Preliminary findings suggest that integrating PK with body composition and PA may help explain variations in PTX toxicities. The PABTOX study will further evaluate these associations, aiming for personalized supportive oncologic care.
Clinical impact:
If confirmed, incorporating body composition and PA into risk assessment could improve toxicity prediction and allow physiotherapists to identify high-risk patients, supporting timely interventions.
This trial is funded by Kom op tegen Kanker (Stand up to Cancer), a project of the Flemish Cancer Society (project ID: 13163).
Keywords
Keyword 1: Breast cancer
Keyword 2: Exercise-pharmacokinetics
Keyword 3: Body composition
Keyword 4: Paclitaxel
| Abstract submitters declaration | yes |
|---|---|
| Conflict of Interest & Ethical Approval | yes |
