Trabectedin for the management of soft-tissue sarcoma

Expert Rev Anticancer Ther. 2009 Jun;9(6):727-37. doi: 10.1586/era.09.28.

Abstract

Trabectedin is a new marine-derived compound that binds the DNA minor groove and interacts with proteins of the DNA-repair machinery. Trabectedin has shown promising single-agent activity in pretreated patients with soft-tissue sarcoma (STS) and ovarian and breast cancer; combination with various other chemotherapeutic drugs is feasible. Toxicities are mainly hematological and hepatic, with grade 3-4 neutropenia and thrombocytopenia observed in approximately 50 and 20% of patients, respectively, and grade 3-4 elevation of liver transaminases observed in 35-50% of patients treated with trabectedin. Trabectedin obtained regulatory approval by the EMEA and in other countries for the treatment of STS patients after failure of all available standard-of-care chemotherapy. Current research focuses on the identification of predictive factors for patients treated with trabectedin as well as the development of other combinations.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents, Alkylating / adverse effects
  • Antineoplastic Agents, Alkylating / pharmacokinetics
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / physiopathology
  • Controlled Clinical Trials as Topic
  • DNA Repair / drug effects
  • Dioxoles / adverse effects
  • Dioxoles / pharmacokinetics
  • Dioxoles / therapeutic use*
  • Female
  • Humans
  • Liver / drug effects
  • Liver / enzymology
  • Neutropenia / chemically induced
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / physiopathology
  • Sarcoma / drug therapy*
  • Sarcoma / physiopathology
  • Tetrahydroisoquinolines / adverse effects
  • Tetrahydroisoquinolines / pharmacokinetics
  • Tetrahydroisoquinolines / therapeutic use*
  • Thrombocytopenia / chemically induced
  • Trabectedin
  • Transaminases / drug effects
  • Transaminases / metabolism

Substances

  • Antineoplastic Agents, Alkylating
  • Dioxoles
  • Tetrahydroisoquinolines
  • Transaminases
  • Trabectedin