title: A phase 2 trial of trabectedin in children with recurrent rhabdomyosarcoma, Ewing sarcoma and non-rhabdomyosarcoma soft tissue sarcomas: a report from the Children's Oncology Group.
abstract: OBJECTIVE
  To determine the toxicity, efficacy and pharmacokinetics of trabectedin given over 24h every 3 weeks to children with recurrent rhabdomyosarcoma, Ewing sarcoma, or non-rhabdomyosarcoma soft tissue sarcomas.
  
  
  METHODS
  Trabectedin was administered as a 24-h intravenous infusion every 21 days. Two dose levels were evaluated (1.3 and 1.5mg/m(2)) for safety; efficacy was then evaluated using a traditional 2-stage design (10+10) at the 1.5mg/m(2) dose level. Pharmacokinetics (day 1 and steady state) were performed during cycle 1.
  
  
  RESULTS
  Fifty patients were enrolled, eight patients at 1.3mg/m(2) and 42 at 1.5mg/m(2). Dose limiting toxicities (DLTs) in the dose finding component included fatigue and reversible GGT elevation in 1/6 evaluable patients at 1.3mg/m(2) and 0/5 at 1.5mg/m(2). Efficacy was evaluated in 42 patients enrolled at the 1.5mg/m(2) dose of whom 22% experienced reversible grade 3 or 4 toxicities that included AST, ALT, or GGT elevations, myelosuppression and deep venous thrombosis. One patient with rhabdomyosarcoma had a partial response and one patient each with rhabdomyosarcoma, spindle cell sarcoma and Ewing sarcoma had stable disease for 2, 3 and 15 cycles, respectively.
  
  
  CONCLUSIONS
  Trabectedin is safe when administered over 24h at 1.5mg/m(2). Trabectedin did not demonstrate sufficient activity as a single agent for children with relapsed paediatric sarcomas.
authors.affiliation: The Hospital for Sick Children, Toronto, ON, Canada. sylvain.baruchel@sickkids.ca
authors.forename: Sylvain
authors.initials: S
authors.lastname: Baruchel
authors.forename: Alberto
authors.initials: A
authors.lastname: Pappo
authors.forename: Mark
authors.initials: M
authors.lastname: Krailo
authors.forename: K Scott
authors.initials: KS
authors.lastname: Baker
authors.forename: Bing
authors.initials: B
authors.lastname: Wu
authors.forename: Doojduen
authors.initials: D
authors.lastname: Villaluna
authors.forename: Michelle
authors.initials: M
authors.lastname: Lee-Scott
authors.forename: Peter C
authors.initials: PC
authors.lastname: Adamson
authors.forename: Susan M
authors.initials: SM
authors.lastname: Blaney
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004149:Dioxoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008495:Medical Oncology / Q000458:organization & administration; D010372:Pediatrics / Q000458:organization & administration; D012208:Rhabdomyosarcoma / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D012509:Sarcoma / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D012512:Sarcoma, Ewing / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D012955:Societies, Medical; D012983:Soft Tissue Neoplasms / Q000188:drug therapy*; D044005:Tetrahydroisoquinolines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077606:Trabectedin; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin