Trabectedin And Indole-3-Carbinol Combination In Heavily Pretreated Metastatic Breast Cancer: Results Of A Pilot Clinical Study

e12015 Background: Trabectedin (T) is a DNA minor groove binder that modulates transcription regulation and modifies tumor microenvironment. It is currently used for the treatment of ovarian cancer and sarcoma and is under evaluation in metastatic breast cancer (mBC). The main toxicities of T are myelosuppression and reversible hepatotoxicity. High dose dexametasone (HD-Dex) reduces T-induced hepatotoxicity but is associated to adverse effects. Indole-3-Carbinol (I3C) was found to protect from T-related hepatotoxicity in pre-clinical models. This pilot study was designed to verify the preclinical findings in the clinic. Methods: 12 heavily pretreated mBC entered the study. Pts were divided in 3 cohorts, receiving dose-escalation of I3C (200, 400 and 600 mg/daily p.o) without HD-Dex pre-medication and T at a fixed dose of 1.3 mg/sqm (q.4wks, in 3hrs). Pts were randomized to receive or not I3C either during the first or the second-T cycle. Liver function, hematology and T-pharmacokinetics (Pk) were serially...