title: Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of trabectedin in a phase II, open-label, multicenter, randomized study in adult patients with unresectable/metastatic liposarcoma or leiomyosarcoma after failure of prior conventional chemotherapy including anthracyclines and ifosfamide.
  
  
  METHODS
  Patients were randomly assigned to one of two trabectedin regimens (via central venous access): 1.5 mg/m(2) 24-hour intravenous infusion once every 3 weeks (q3 weeks 24-hour) versus 0.58 mg/m(2) 3-hour IV infusion every week for 3 weeks of a 4-week cycle (qwk 3-hour). Time to progression (TTP) was the primary efficacy end point, based on confirmed independent review of images.
  
  
  RESULTS
  Two hundred seventy patients were randomly assigned; 136 (q3 weeks 24-hour) versus 134 (qwk 3-hour). Median TTP was 3.7 months versus 2.3 months (hazard ratio [HR], 0.734; 95% CI, 0.554 to 0.974; P = .0302), favoring the q3 weeks 24-hour arm. Median progression-free survival was 3.3 months versus 2.3 months (HR, 0.755; 95% CI, 0.574 to 0.992; P = .0418). Median overall survival (n = 235 events) was 13.9 months versus 11.8 months (HR, 0.843; 95% CI, 0.653 to 1.090; P = .1920). Although somewhat more neutropenia, elevations in AST/ALT, emesis, and fatigue occurred in the q3 weeks 24-hour, this regimen was reasonably well tolerated. Febrile neutropenia was rare (0.8%). No cumulative toxicities were noted.
  
  
  CONCLUSIONS
  Prior studies showed clinical benefit with trabectedin in patients with sarcomas after failure of standard chemotherapy. This trial documents superior disease control with the q3 weeks 24-hour trabectedin regimen in liposarcomas and leiomyosarcomas, although the qwk 3-hour regimen also demonstrated activity relative to historical comparisons. Trabectedin may now be considered an important new option to control advanced sarcomas in patients after failure of available standard-of-care therapies.
authors: Center for Sarcoma and Bone Oncology and Ludwig Center of Dana-Farber/Harvard Cancer Center, Dana-Farber Cancer Institute, D1212; 44 Binney St, Boston, MA 02115, USA. gdemetri@partners.org
authors: George D
authors: GD
authors: Demetri
authors: Sant P
authors: SP
authors: Chawla
authors: Margaret
authors: M
authors: von Mehren
authors: Paul
authors: P
authors: Ritch
authors: Laurence H
authors: LH
authors: Baker
authors: Jean Y
authors: JY
authors: Blay
authors: Kenneth R
authors: KR
authors: Hande
authors: Mary L
authors: ML
authors: Keohan
authors: Brian L
authors: BL
authors: Samuels
authors: Scott
authors: S
authors: Schuetze
authors: Claudia
authors: C
authors: Lebedinsky
authors: Yusri A
authors: YA
authors: Elsayed
authors: Miguel A
authors: MA
authors: Izquierdo
authors: Javier
authors: J
authors: Gómez
authors: Youn C
authors: YC
authors: Park
authors: Axel
authors: A
authors: Le Cesne
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D001315:Australia; D004149:Dioxoles / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005060:Europe; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D007890:Leiomyosarcoma / Q000188:drug therapy* / Q000556:secondary; D008080:Liposarcoma / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009656:North America; D016016:Proportional Hazards Models; D018570:Risk Assessment; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D000077606:Trabectedin; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin; D007069:Ifosfamide