Which are the interactions between baseline body mass index (BMI), toxicity of chemotherapy (CT), and efficacy of adjuvant treatments? 9-year follow-up results of French Adjuvant Study Group (FASG) trials

Abstract

550 Objective: The aim of our analysis was to determine the role of BMI on toxicities of adjuvant CT, and if the efficacy of adjuvant treatments was modified by an abnormal BMI (abBMI). Methods: Among the 8 FASG trials, 3,144 patients (pts) were assessable: 1,618 received adjuvant CT alone, 890 CT plus tamoxifen (Tam), 441 hormonotherapy alone, and 195 no systemic treatment. In 2,508 pts receiving CT, it was FEC regimens (epirubicin [E] 50,75, or 100 mg/m2) in 68%, and other E-based CT in the others. The median follow-up was 9 years. BMI = weight (kg)/[size (m)]2: abBMI value was defined as > 27 (WHO classification). We compared pts characteristics and toxicities according to BMI. Then, disease-free (DFS) and overall survival (OS) were computed in a multivariate model according to adjuvant treatment. Results: Median BMI was 24 kg/m2 with 810 (26%) pts > 27. AbBMI was significantly more frequent in menopausal pts, if tumor size > 2 cm, N > 3, and progesterone receptors positive (PR+). Mean E cumulative dose delivered was higher in abBMI pts (342 v 326 mg/m2, P = .009). AbBMI pts had less grade 3–4 neutropenia (11.2% v 14.7%, P = .001), and more left ventricular dysfunction (1.8% v 0.9%, P = .03). In pts receiving E > 450 mg/m2, abBMI pts had less alopecia (P = .03) and more asthenia (P = .01). The 9-year DFS and OS were significantly worse in abBMI pts (54.7% v 59.8, P = .01; 62.3%v 68.3%, P = .0003, respectively). The multivariate analysis showed that abBMI had no prognostic value for relapse in pts receiving Tam alone or no systemic treatment, but was an independent prognostic factor of relapse in pts receiving CT combined or no with Tam (P = .02, and P = .002, respectively). Conclusion: AbBMI pts had less acute toxicity of CT, but developed more delayed cardiac toxicity irrespective of dose. The efficacy of hormonal treatment was not modified by BMI. It seems that an abBMI decreased the effect of CT whereas these pts received higher E dose. Probably, CT drugs have a modified distribution profile in these pts and these findings questioned about the dose calculation in mg/m2 when BMI is upper normal value. No significant financial relationships to disclose.