title: A retrospective analysis of antitumour activity with trabectedin in translocation-related sarcomas.
abstract: OBJECTIVE
  Approximately 20% of soft tissue sarcomas (STS) have subtype-specific chromosomal translocations; these generate chimeric oncoproteins which can act as abnormal transcription factors. Since trabectedin can bind to DNA and displace transcription factors, antitumour activity was explored in translocation-related sarcoma (TRS) subtypes.
  
  
  METHODS
  The current retrospective pooled analysis includes data from 81 patients with TRS treated in 8 phase II trials.
  
  
  RESULTS
  TRS subtypes were: synovial sarcoma (SS, n=45), myxoid-round cell liposarcoma (MRC-L-sarcoma, n=27), alveolar soft part sarcoma (ASPS, n=4), endometrial stromal sarcoma (ESS, n=3) and clear cell sarcoma (CCS, n=2). All but one patient had received prior chemotherapy (median of 2 lines). Patients received a median of 4 trabectedin cycles (range, 1-48; median dose intensity=0.40 mg/m(2)/week). Partial responses according to Response Evaluation Criteria in Solid Tumours (RECIST) occurred in 8 patients (ORR=10%; 95% CI, 4-19%): four in MRC-L-sarcoma; three in SS and one in ESS. Tumour control rate (ORR plus stable disease) was 59% (95% CI, 48-70%). Median PFS was 4.1 months (6-month PFS rate=40%). Median overall survival was 17.4 months (survival rate at 12 months=60%). Trabectedin had a manageable safety profile.
  
  
  CONCLUSIONS
  Trabectedin demonstrates encouraging disease control in TRS. Since these promising results were generally noted in patients following chemotherapy, a phase III randomised trial in first-line is ongoing to compare trabectedin with doxorubicin-based chemotherapy in patients with TRS.
authors: Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France. lecesne@igr.fr.
authors: Axel
authors: A
authors: Le Cesne
authors: Sara
authors: S
authors: Cresta
authors: Robert G
authors: RG
authors: Maki
authors: Jean Yves
authors: JY
authors: Blay
authors: Jaap
authors: J
authors: Verweij
authors: Andrés
authors: A
authors: Poveda
authors: Paolo G
authors: PG
authors: Casali
authors: Carme
authors: C
authors: Balaña
authors: Patrick
authors: P
authors: Schöffski
authors: Federica
authors: F
authors: Grosso
authors: Pilar
authors: P
authors: Lardelli
authors: Antonio
authors: A
authors: Nieto
authors: Vicente
authors: V
authors: Alfaro
authors: George D
authors: GD
authors: Demetri
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; 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*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012509:Sarcoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D044005:Tetrahydroisoquinolines / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D000077606:Trabectedin; D014178:Translocation, Genetic; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin