Initial chemotherapy dose reductions and subsequent treatment delivery in stage I-IIIA breast cancer.

Overview

abstract

BACKGROUND: For most cytotoxic drugs, guidelines recommend body-surface-area-based dosing, yet some patients start with reduced doses, potentially reflecting tolerability concerns. The relationship between first-cycle dose reductions and subsequent delivery is unclear. METHODS: The authors analyzed data from women with stage I-IIIA breast cancer treated with adjuvant chemotherapy. Sankey diagrams illustrated trajectories from first-cycle dose proportion (FCDP) to average relative dose intensity (ARDI, ratio of received to expected dose intensity across the regimen), and cumulative dose proportion (CDP, ratio of total received to expected dose). Poisson regression estimated adjusted prevalence ratios for reduced FCDP (<95% vs. ≥95%) and three outcomes: ARDI reduction beyond initial FCDP, receiving fewer cycles, and CDP reduction beyond initial FCDP. Analyses assessed effect modification by age, body mass index (BMI), and comorbidities. Dosing was analyzed for cytotoxic and HER2-targeted therapy. RESULTS: A total of 8772 (90.8%) patients started with FCDP ≥95%; most maintained ARDI ≥95% (65.1%) and CDP ≥95% (79.9%). In multi-variable models, FCDP <95% was not significantly associated with further ARDI or CDP reductions or receipt of fewer cycles. BMI modified these associations (p-interaction = .004 for fewer cycles; p-interaction = .03 for CDP), with positive associations among overweight but not obese or normal-weight patients. FCDP <95% was linked to a lower likelihood of further ARDI reductions for both therapy types and lower likelihood of cumulative dose reduction in HER2-targeted therapy. CONCLUSIONS: Early dosing decisions shaped subsequent chemotherapy delivery. Most patients who began at full dose maintained consistent dosing, whereas early reductions did not stave off subsequent changes, underscoring the need to balance safety with adequate dose intensity.