6533b7d0fe1ef96bd125b663

RESEARCH PRODUCT

BMI as a risk factor for toxicities in patients with advanced soft tissue sarcoma treated with trabectedin.

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e22517 Background: Since the first steps of its clinical development, trabectedin was noticed to be extremely active against myxoid liposarcoma (MLS), whose pathogenesis seems to be associated to the presence of the t(12;16)(q13;p11) translocation, resulting in the expression of FUS-DDIT3 fusion genes. Therefore, the drug seems to induce a maturation of MLS lipoblasts, with transition of the residual spindle non-lipogenic cells into mature vacuolated lipoblasts. This effect could be prevented by the increase of leptin circulating levels in obese patients. For these reasons we designed this retrospective analysis in order to evaluate the BMI status (measure of total adipose content) as a predictors or efficacy of trabectedin in MLS patients. Methods: Patients were treated in cancer centers with trabectedin at the approved dose of 1.5 mg/m2, given as a 24-hour infusion every 3 weeks. This retrospective analysis was preformed on the basis of clinical charts or databases. For the purpose of this analysis only patient with a BMI > 18.5 were included and an the population divided into two categories: normal weight if BMI < 25, overweight > 25. An analysis of the correlation between BMI and objective response (OR) rate, tumor control (TC) rate (OR+stable disease lasting ≥3 months), progression-free survival (PFS) and overall survival (OS) was performed. Results: 62 adult patients with recurrent MLS were enrolled (M/F: 33/29; median age: 53 ys). All patients were doxorubicin-pretreated. The median BMI in the whole population was 22.5 (range: 1.85 – 29.8). No statistically significant differences were identified in terms of OR or TC. On the contrary, PFS (6.8 vs. 3.7 months; p< 0.026, log rank test) and OS (14.9 vs. 8.3 months; p< 0.0001, log rank test) were significantly prolonged in normal weighted patients vs over weighted patients. Six and 12-months Kaplan-Meier PFS estimates and survival rates at 12, 24 and 36 months were also better in those patients. Conclusions: these results seem confirm a role o adipose content as a predictor of resistance to trabectedin in MLS patients. Further studies are warranted to confirm this preliminary observation and understand the biological mechanisms of this relationship.