Phase II randomized study of trabectedin given as two different every 3 weeks dose schedules (1.5 mg/m2 24 h or 1.3 mg/m2 3 h) to patients with relapsed, platinum-sensitive, advanced ovarian cancer

Ann Oncol. 2009 Nov;20(11):1794-802. doi: 10.1093/annonc/mdp198. Epub 2009 Jun 25.

Abstract

Background: This randomized, open-label, phase II clinical trial evaluated the optimal regimen of trabectedin administered every 3 weeks in patients with platinum-sensitive, relapsed, advanced ovarian cancer (AOC).

Patients and methods: Patients previously treated with less than two or two previous chemotherapy lines were randomized to receive trabectedin 1.5 mg/m(2) 24 h (arm A, n = 54) or 1.3 mg/m(2) 3 h (arm B, n = 53). Objective response rate (ORR) per RECIST was the primary efficacy end point. Toxic effects were graded according to the National Cancer Institute-Common Toxicity Criteria v. 2.0.

Results: ORR was 38.9% [95% confidence interval (CI) 25.9% to 53.1%; arm A] and 35.8% (95% CI 23.1% to 50.2%; arm B) (intention-to-treat primary analysis). Median time to progression was 6.2 months (95% CI 5.3-8.6 months; arm A) and 6.8 months (95% CI 4.6-7.4 months; arm B). Frequent severe adverse events were nausea/vomiting (24%, arm A; 15%, arm B) and fatigue (15%, arm A; 10%, arm B). Common severe laboratory abnormalities were transient, noncumulative neutropenia (55%, arm A; 37%, arm B) and transaminase increases (alanine aminotransferase, 55%, arm A; 59%, arm B).

Conclusions: Both every-3-weeks trabectedin regimes, 1.5 mg/m(2) 24 h and 1.3 mg/m(2) 3 h, were active and reasonably well tolerated in AOC platinum-sensitive patients. Trabectedin every-3-weeks has promising activity and deserves to be further evaluated in relapsed AOC.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / administration & dosage*
  • Antineoplastic Agents, Alkylating / adverse effects
  • Dioxoles / administration & dosage*
  • Dioxoles / adverse effects
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Ovarian Neoplasms / drug therapy*
  • Platinum Compounds / therapeutic use
  • Tetrahydroisoquinolines / administration & dosage*
  • Tetrahydroisoquinolines / adverse effects
  • Trabectedin

Substances

  • Antineoplastic Agents, Alkylating
  • Dioxoles
  • Platinum Compounds
  • Tetrahydroisoquinolines
  • Trabectedin