title: Trabectedin in soft tissue sarcomas.
abstract: Soft tissue sarcomas are a group of rare tumors derived from mesenchymal tissue, accounting for about 1% of adult cancers. There are over 60 different histological subtypes, each with their own unique biological behavior and response to systemic therapy. The outcome for patients with metastatic soft tissue sarcoma is poor with few available systemic treatment options. For decades, the mainstay of management has consisted of doxorubicin with or without ifosfamide. Trabectedin is a synthetic agent derived from the Caribbean tunicate, Ecteinascidia turbinata. This drug has a number of potential mechanisms of action, including binding the DNA minor groove, interfering with DNA repair pathways and the cell cycle, as well as interacting with transcription factors. Several phase II trials have shown that trabectedin has activity in anthracycline and alkylating agent-resistant soft tissue sarcoma and suggest use in the second- and third-line setting. More recently, trabectedin has shown similar progression-free survival to doxorubicin in the first-line setting and significant activity in liposarcoma and leiomyosarcoma subtypes. Trabectedin has shown a favorable toxicity profile and has been approved in over 70 countries for the treatment of metastatic soft tissue sarcoma. This manuscript will review the development of trabectedin in soft tissue sarcomas.
authors: University of Washington, 1959 NE Pacific St, Seattle, WA 98195, USA. bpetek@uw.edu.
authors: Bradley J
authors: BJ
authors: Petek
authors: Fred Hutchinson Cancer Research Center, University of Washington, 825 Eastlake Avenue East, G-3630, Seattle, WA 98109-1023, USA. eloggers@seattlecca.org.
authors: Elizabeth T
authors: ET
authors: Loggers
authors: Fred Hutchinson Cancer Research Center, University of Washington, 825 Eastlake Avenue East, G-3630, Seattle, WA 98109-1023, USA. spollack@fhcrc.org.
authors: Seth M
authors: SM
authors: Pollack
authors: Fred Hutchinson Cancer Research Center, University of Washington, 825 Eastlake Avenue East, G-3630, Seattle, WA 98109-1023, USA. rjones@seattlecca.org.
authors: Robin L
authors: RL
authors: Jones
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D004149:Dioxoles / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D012509:Sarcoma / Q000188:drug therapy*; D044005:Tetrahydroisoquinolines / Q000009:adverse effects / Q000627:therapeutic use*; D000077606:Trabectedin
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin