title: Experience of the use of trabectedin (ET-743, Yondelis) in 21 patients with pre-treated advanced sarcoma from a single centre.
abstract: OBJECTIVE
  Trabectedin (ET-743, Yondelis) is a marine-derived alkaloid that has two actions. It binds in the minor groove of DNA resulting in a conformational change; thus potentially altering interactions with transcription factors and other DNA binding proteins and it also interacts with the transcription-coupled nucleotide excision repair machinery to induce lethal double-stranded DNA breaks. In recent phase II trials it has shown considerable activity in the treatment of sarcomas. Here the use of trabectedin in patients with advanced refractory sarcoma from a single institution is presented.
  
  
  METHODS
  Twenty-one patients with advanced refractory sarcoma from a single UK centre were treated with trabectedin on a named patient compassionate basis programme. All patients had received prior treatment with an anthracycline, and 95% had received ifosfamide.
  
  
  RESULTS
  The patients received a median of four cycles of treatment. Objective partial responses were seen in three patients (14%) and a further eight patients (38%) achieved durable stable disease for a median duration of 4.5 months. The estimated 3- and 6-month progression-free survival was 58.8 and 17.6%, respectively. Six patients experienced early disease progression, and four patients died while on treatment. One death was due to treatment-related toxicity. Overall the drug was relatively well tolerated, with hepatic and haematological toxicities most commonly encountered. Both necessitated delays and/or dose reductions in a proportion of patients. Other significant toxicities were nausea, vomiting and asthenia.
  
  
  CONCLUSIONS
  The disease responses and durable nature of disease stabilisation seen in a proportion of our patients support the continued investigational use of this drug in the treatment of advanced soft tissue sarcomas.
authors.affiliation: The London Bone and Soft Tissue Tumour Service, Department of Oncology, University College Hospital, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Roylance
authors.forename: B
authors.initials: B
authors.lastname: Seddon
authors.forename: A
authors.initials: A
authors.lastname: McTiernan
authors.forename: K
authors.initials: K
authors.lastname: Sykes
authors.forename: S
authors.initials: S
authors.lastname: Daniels
authors.forename: J
authors.initials: J
authors.lastname: Whelan
mesh_terms: D000293:Adolescent; D000328:Adult; D018943:Anthracyclines / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004149:Dioxoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D044005:Tetrahydroisoquinolines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D000077606:Trabectedin; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D018943:Anthracyclines; D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin; D007069:Ifosfamide