Patterns of tumor response to trabectedin (ET743) in myxoid liposarcomas

Abstract

9511 Background: Trabectedin (T) is a marine-derived agent found to be active in ovarian cancer and sarcomas. Among sarcomas, activity has been notable in leiomyosarcomas and liposarcomas. Since liposarcomas are a heterogeneous group, including well/de-differentiated, pleomorphic, and myxoid/round cell subtypes, we have noted particularly interesting patterns of responsiveness to T in myxoid liposarcomas, which are associated with t(12;16)(q13;p11) or t(12;22)(q13;q12) chromosomal translocations, resulting in CHOP-TLS or CHOP-EWS fusion products. Methods: 15 cases of myxoid liposarcomas treated with T at the Istituto Nazionale Tumori, Milan, were retrospectively reviewed. In most cases, T was given as a 24-hr continuous infusion every 21 days, at dose levels from 1.0 to 1.5 mg/sqm. 108 courses were delivered, with a median of 5 courses per patient (range 2–20). Observations made in this series were shared with five other institutions having treated myxoid liposarcoma cases with T, all of which also report a significant response rate, for a total of 44 pts. A centralized radiological review of all pts is ongoing. Results: In the Milan series, early tissue alterations in tumors were observed in 14 patients, mainly with a decrease in tumor density on CT scan and/or decrease in contrast enhancement on MRI. These changes were followed by tumor shrinkage amounting to a conventional PR/CR in 8 (pending final review), while 3 others have responses which continue to evolve. Progression followed treatment interruption in one patient, with a minor response occurring at treatment restart. Treatment is continuing in 12 pts (median duration of therapy in excess of 5 months). Further results of the central radiological review from all centres will be reported. Conclusions: Tumor response to T seen in myxoid liposarcoma appears to be marked by early radiological alterations in tumor tissue, often preceding tumor shrinkage, which may be delayed. A selective mechanism of action for this chromosomal translocation-related sarcoma is suggested, and is being actively investigated at the moment. [Table: see text]