Trabectedin: an anticancer drug from the sea.
BACKGROUND
Trabectedin (ET-743) is an anticancer agent originally isolated from Ecteinascidia turbinata, a marine organism.


OBJECTIVE
The goal of this review is to describe the chemical characteristics, mechanism of action and the results of clinical trials with this compound. The toxicities are described, as well as the pharmacokinetics. The regulatory affairs and marketing strategies for this compound are also discussed.


METHODS
Medline and meeting proceedings were searched to accomplish our objectives.


CONCLUSIONS
Trabectedin is a unique alkylating agent. It affects a variety of transcription factors, cell proliferation, and nucleotide excision repair mechanism. In addition, it inhibits the MDR-1 gene, which is responsible for the resistance of cancer cells to chemotherapeutic agents. The main toxicities of this agent are transaminitis and myelosuppression, both reversible and noncumulative. At present, trabectedin is approved in Europe for the treatment of sarcoma. The combination of this compound with other chemotherapeutics has been tested in Phase I studies in sarcomas and is feasible. This drug in combination with doxil has shown to improve outcome in relapsed ovarian cancer, compared with doxil alone. The results of this study may lead to an FDA approval of the combination in the USA, for the treatment of relapsed ovarian cancer.
Ganjoo
Kristen N
KN
Stanford University, 875 Blake Wilbur Drive, Stanford, CA 94305, USA kganjoo@stanford.edu
Patel
S R
SR
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004149:Dioxoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D044005:Tetrahydroisoquinolines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077606:Trabectedin
D000970:Antineoplastic Agents; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin