Final results of a combination study between trabectedin and pegylated liposomal doxorubicin (PLD) in patients with advanced malignancies

3074 Background: Trabectedin (Yondelis, ET-743) is a marine-derived compound, which binds to the minor groove of DNA and is active at nM concentrations. Trabectedin is thought to act through the transcription-coupled nucleotide excision repair system. In clinical studies trabectedin has demonstrated activity in soft tissue sarcoma, ovarian and breast cancer. Methods: Eligibility criteria included normal liver function tests, limited prior doxorubicin exposure (≤ 250 mg/m2), and normal cardiac function. PLD 30 mg/m2 was administered i.v. over one hour followed immediately by one of six trabectedin doses (0.4, 0.6, 0.75, 0.9, 1.1, and 1.3 mg/m2) i.v. over 3 hours every 21 days. The effect of the combination on the liver morphology was evaluated in biopsies obtained from consenting patients. Results: Six dose levels of trabectedin were evaluated. The DLTs were one grade 3 AST and two grade 4 ALT elevations observed at a trabectedin dose of 1.3 mg/m2. The recommended dose is trabectedin 1.1 mg/m2 plus PLD 30 ...