title: Major efficacy of trabectedin in 2 metastatic osteosarcoma patients with wild-type Asp1104 ERCC5 tumor status.
abstract: BACKGROUND
  Treatment of osteosarcoma of the extremities consists of surgical resection preceded and followed by chemotherapy, including high-dose methotrexate or adriamycin-based protocols. When distant relapse occurs, therapeutic options are scarce. Trabectedin, a DNA-binding agent, is indicated for the treatment of patients with advanced soft tissue sarcomas after failure of anthracyclines and ifosfamide. In this indication, the 6-month progression-free survival is about 35-40%. Recent reports showed that some specific single nucleotide polymorphisms (SNPs) from DNA repair genes could be associated with sensitivity to trabectedin in soft tissue sarcomas.
  
  
  METHODS
  We report our experience of 2 metastatic, heavily pre-treated osteosarcoma patients who were treated with trabectedin. Pyrosequencing analyses of tumors from both patients for several SNPs of the ERCC1, ERCC5 and BRAC1 genes were performed. Both patients showed major response to trabectedin, which was interestingly related with homozygoty of the common guanine allele of ERCC5 (G/G genotype; Asp/Asp) after pyrosenquencing analysis of tumors from both patients. This polymorphism was previously shown to be associated with better outcome in soft tissue sarcoma patients treated with trabectedin.
  
  
  CONCLUSIONS
  Homozygoty for the wild-type Asp1104 SNP of the ERCC5 gene was found in 2 cases of relapsed osteosarcoma, who responded to trabectedin.
authors.affiliation: Medical Oncology Department, Centre Antoine Lacassagne, Nice, France.
authors.forename: Lauris
authors.initials: L
authors.lastname: Gastaud
authors.forename: Esma
authors.initials: E
authors.lastname: Saâda-Bouzid
authors.forename: Valérie
authors.initials: V
authors.lastname: Le Morvan
authors.forename: Philippe
authors.initials: P
authors.lastname: Pourquier
authors.forename: Antoine
authors.initials: A
authors.lastname: Ianessi
authors.forename: Juliette
authors.initials: J
authors.lastname: Thariat
authors.forename: Antoine
authors.initials: A
authors.lastname: Italiano
authors.forename: Antoine
authors.initials: A
authors.lastname: Thyss
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000235:genetics; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004149:Dioxoles / Q000627:therapeutic use*; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044005:Tetrahydroisoquinolines / Q000627:therapeutic use*; D000077606:Trabectedin; D014157:Transcription Factors / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D004149:Dioxoles; D004720:Endonucleases; D005819:Genetic Markers; D009687:Nuclear Proteins; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5