Pharmacologic de-escalation of dexamethasone during weekly paclitaxel: a randomized phase III trial evaluating...

Dexamethasone is routinely used as premedication during weekly paclitaxel to prevent hypersensitivity reactions; however, prolonged corticosteroid exposure may induce clinically relevant metabolic, endocrine, and patient-reported adverse effects. This study evaluated whether selective omission of dexamethasone after the second paclitaxel infusion is safe and explored its effects on quality of life, metabolic/endocrine parameters, and short-term oncologic outcomes, including recurrence and disease-related mortality.

In this prospective, randomized, open-label phase III trial, 86 women with stage I-III breast cancer receiving neoadjuvant or adjuvant AC-T or AC-TH chemotherapy were randomized 1:1 to standard dexamethasone premedication or omission after the second weekly paclitaxel infusion. The primary endpoint was safety, defined by hypersensitivity reactions and adverse events. Secondary and exploratory endpoints included patient-reported quality of life using the EORTC QLQ-C30, metabolic and endocrine parameters, and short-term oncologic outcomes. Longitudinal changes were analyzed using generalized estimating equations.

Eighty-four patients were included in the final analysis. No hypersensitivity reactions occurred after dexamethasone omission, and treatment completion rates were comparable between groups. After a median follow-up of 3.15 years, recurrence and disease-related mortality were similar between groups in descriptive analyses. The omission strategy was associated with improvements in role functioning and reduced worsening of pain (p = 0.02), constipation (p = 0.01), and nausea/vomiting (p = 0.03). No statistically significant differences were observed for emotional or physical functioning. Endocrine analyses demonstrated reduced IGF-1 levels and a trend toward lower insulin levels. These secondary analyses should be interpreted as exploratory.

Selective omission of dexamethasone after the second weekly paclitaxel infusion was safe and well tolerated in this randomized trial. The findings support the feasibility of a corticosteroid-sparing strategy during weekly paclitaxel and suggest potential benefits in selected patient-reported and endocrine outcomes, which warrant confirmation in larger studies.

NCT04350229, registered on 16 April 2020.