title: A retrospective pooled analysis of trabectedin safety in 1,132 patients with solid tumors treated in phase II clinical trials.
abstract: OBJECTIVE
  To summarize the safety experience obtained from phase II clinical trials conducted with trabectedin as single-agent therapy in patients with advanced solid tumors.
  
  
  METHODS
  This retrospective analysis includes 1,132 patients exposed to trabectedin in 19 phase II trials carried out between February 1999 and April 2008. Trabectedin was administered intravenously as 1 of 3 schedules: 24-hour infusion every 3 weeks (q3wk 24-h; n = 570/2,818 cycles), 3-hour infusion every 3 weeks (q3wk 3-h; n = 258/1,003 cycles), and 3-hour infusion for three consecutive weeks every 4 weeks (qwk 3-h; n = 304/1,198 cycles).
  
  
  RESULTS
  The majority of patients (90%) had received previous chemotherapy. Patients were given a median of three treatment cycles of trabectedin (range, 1-59). Nausea, fatigue and vomiting were the most common trabectedin-related adverse events, reported in ≥20% of patients. Reversible myelosuppression (mainly neutropenia) and transient reversible transaminase increases were the most common laboratory abnormalities seen with trabectedin, with a very low incidence of relevant clinical consequences. Deaths associated with drug-related adverse events were infrequent, occurring in 19 (1.7%) patients.
  
  
  CONCLUSIONS
  Single-agent trabectedin treatment was reasonably well tolerated. Trabectedin can be administered for prolonged periods to patients with sustained clinical benefit (induction of disease stability or shrinkage) without cumulative toxicities over time.
authors.affiliation: Department of Medicine, Institut Gustave Roussy, 94805, Villejuif Cedex, France. lecesne@igr.fr
authors.forename: Axel
authors.initials: A
authors.lastname: Le Cesne
authors.forename: Alejandro
authors.initials: A
authors.lastname: Yovine
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay
authors.forename: Suzette
authors.initials: S
authors.lastname: Delaloge
authors.forename: Robert G
authors.initials: RG
authors.lastname: Maki
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Misset
authors.forename: Pilar
authors.initials: P
authors.lastname: Frontelo
authors.forename: Antonio
authors.initials: A
authors.lastname: Nieto
authors.forename: Juhui James
authors.initials: JJ
authors.lastname: Jiao
authors.forename: George D
authors.initials: GD
authors.lastname: Demetri
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D004149:Dioxoles / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D012206:Rhabdomyolysis / Q000139:chemically induced; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage* / Q000009:adverse effects; D000077606:Trabectedin; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D000410:Alanine Transaminase; D000077606:Trabectedin