The association of body mass index with safety and effectiveness of first-line carboplatin-based chemotherapy in patients with metastatic non-small cell lung cancer

Abstract

Introduction: Carboplatin is an anticancer drug used for treatment of various types of cancer including non-small cell lung cancer (NSCLC). Dosing is based on estimated glomerular filtration rate (GFR) using the Cockcroft-Gault formula. In overweight patients, the GFR is more likely overestimated, resulting in a potentially overdose of carboplatin affecting treatment response. This study investigated the association of body mass index (BMI) on overall survival (OS) and progression-free survival (PFS) in stage-IV NSCLC patients treated with first-line carboplatin-based chemotherapy. Secondary safety endpoints were thrombocytopenia and toxicity-related hospitalizations.

Materials and methods: This was a retrospective multicenter cohort study. Patients were categorized according to BMI<25.0 kg/m² (normal weight and reference), 25.0-29.9 kg/m² (overweight) or ≥30.0 kg/m² (obese). For survival analyses adjusted hazard ratios [aHR] were calculated using multivariate Cox regression analysis. Secondary outcomes were analyzed using multivariate logistic regression providing adjusted odd ratios [aOR].

Results: Overweight patients (n=174) had a significantly better OS (aHR=0.72, 95%-CI:0.59-0.89) and PFS (aHR=0.74, 95%-CI:0.61-0.90) compared to normal weight patients (n=268). OS nor PFS were different in obese (n=51) compared to normal weight patients. However, obesity was associated with significantly higher incidences of thrombocytopenia grade ≥3 (aOR=3.47, 95%-CI:1.75-6.90).

Conclusion: This study shows a significantly longer survival for overweight compared to normal weight patients. Obese patients have an increased risk for grade ≥3 thrombocytopenia without a difference in survival following carboplatin-based chemotherapy. The implications for clinical practice are to use the Cockcroft-Gault formula with caution in patients with BMI≥30.0 kg/m², and to verify calculated dosing of carboplatin for appropriateness.

Keywords: BMI; NSCLC; Overdosing; Overweight; Survival; Toxicity.