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

George D. Demetri, Sant P. Chawla, Margaret Von Mehren, Paul Ritch, Laurence H. Baker, Jean Y. Blay, Kenneth R. Hande, Mary L. Keohan, Brian L. Samuels, Scott Schuetze, Claudia Lebedinsky, Yusri A. Elsayed, Miguel A. Izquierdo, Javier Gómez, Youn C. Park, Axel Le Cesne

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473 Scopus citations

Abstract

Purpose: 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. Patients and Methods: Patients were randomly assigned to one of two trabectedin regimens (via central venous access): 1.5 mg/m2 24-hour intravenous infusion once every 3 weeks (q3 weeks 24-hour) versus 0.58 mg/m2 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)4188-4196
Number of pages9
JournalJournal of Clinical Oncology
Volume27
Issue number25
DOIs
StatePublished - Sep 1 2009

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Anthracyclines/therapeutic use
  • Antibiotics, Antineoplastic/therapeutic use
  • Antineoplastic Agents, Alkylating/administration & dosage
  • Australia
  • Dioxoles/administration & dosage
  • Disease-Free Survival
  • Drug Administration Schedule
  • Drug Resistance, Neoplasm
  • Europe
  • Female
  • Humans
  • Ifosfamide/therapeutic use
  • Infusions, Intravenous
  • Kaplan-Meier Estimate
  • Leiomyosarcoma/drug therapy
  • Liposarcoma/drug therapy
  • Male
  • Middle Aged
  • Neoplasm Staging
  • North America
  • Proportional Hazards Models
  • Risk Assessment
  • Tetrahydroisoquinolines/administration & dosage
  • Time Factors
  • Trabectedin
  • Treatment Failure
  • Young Adult

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