Muscle mass influences paclitaxel systemic exposure, may guide personalized dosing

Extending the infusion duration of paclitaxel in breast cancer patients with low skeletal muscle area is expected to reduce peripheral neuropathy while maintaining systemic exposure, suggests a study.

This finding implies the improvement of treatment outcomes by personalizing paclitaxel dosing based on the patient’s body composition.

A team of investigators conducted a secondary analysis of female patients with breast cancer scheduled to receive 80 mg/m² weekly paclitaxel infusions. They measured paclitaxel at the end of initial infusion to estimate the maximum concentration (C_max).

Twenty-nine body composition features for inclusion in pharmacokinetic modelling were measured using computed tomography (CT) scans. The investigators also performed Monte Carlo simulations to identify infusion durations that limit the probability of exceeding C_max >2,885 ng/mL, which was selected based on prior work linking this to an unacceptable risk of peripheral neuropathy.

Thirty-nine patients met the eligibility criteria for analysis. A two-compartment pharmacokinetic model with T11 skeletal muscle area as a covariate of paclitaxel volume of distribution (Vd) was deemed the optimal model.

In Monte Carlo simulations, infusion extension of standard paclitaxel dose from 1 hour to 2 and 3 hours in patients who have skeletal muscle area 4,907–7,080 mm² and <4,907 mm², respectively, would limit the risk of C_max >2,885 ng/mL to <50 percent. This could result in reduced neuropathy, with a marginal increase in overall systemic paclitaxel exposure.

“Patients with low muscle mass have increased risk of paclitaxel-induced peripheral neuropathy, which is dependent on systemic paclitaxel exposure,” the investigators said. “Dose optimization may be feasible through the secondary use of radiologic data for body composition.”