Trabectedin: the evidence for its place in therapy in the treatment of soft tissue sarcoma
Katherine A Thornton
Sidney Kimmel Comprehensive Cancer Center at The Johns Hopkins University, Baltimore, MD, USA
Introduction: Soft tissue sarcoma accounts for less than 1% of all malignant neoplasms and is comprised of a very heterogeneous group of tumors with over 50 different subtypes. Due to its diversity and rarity, developing new therapeutics has been difficult, at best. The standard of care in the treatment of advanced and metastatic disease over the last 30 years has been doxorubicin and ifosfamide, either alone or in combination. There has been significant focus on developing new therapeutics to treat primary and metastatic disease. Trabectedin (ecteinascidin-743) is a tetrahydroisoquinoline alkaloid which has been evaluated in the treatment of metastatic soft tissue sarcoma.
Aims: To review the current evidence for the therapeutic use of trabectedin in patients with soft tissue sarcoma.
Evidence review: Five phase I studies in patients with solid tumors, all of which include sarcoma patients, evaluating the dosing and toxicity of trabectedin were performed with efficacy being evaluated as a secondary endpoint. Additionally, there are four phase I trials evaluating trabectedin in combination with frontline therapeutic drugs in soft tissue sarcoma. Four phase II studies were performed in soft-tissue sarcoma patients with objective response rates ranging from 3.7% to 17.1%. Additionally, in two compassionate use trials, objective response rates between 14% and 51% were seen, the largest response resulting from a study specifically focusing on liposarcoma.
Place in therapy: Trabectedin is a potential therapeutic option for the management of softtissue sarcoma. It appears to have specific activity in a select group of histologies, most notably myxoid/round cell liposarcoma. Although it would be helpful to study the use of trabectedin in a randomized, controlled fashion, the relative rarity of soft-tissue sarcoma, and heterogeneity of the histologic subtypes, makes phase III trials a difficult prospect.
Keywords: soft tissue sarcoma, metastatic, trabectedin, ET-743, Yondelis®
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