Trabectedin

Trabectedin is a marine-derived alkaloid (from Ecteinascidia turbinata) that binds to the minor groove of DNA, forming covalent adducts that bend the DNA helix toward the major groove. These adducts interfere with transcription factor binding and nucleotide excision repair (NER) machinery — uniquely, cells with functional NER are MORE sensitive to trabectedin because NER processing of trabectedin-DNA adducts generates lethal strand breaks. It also modulates the tumor microenvironment by depleting tumor-associated macrophages.

Adult

Administered as a 24-hour infusion of 1.3 mg/m2 every 3 weeks. It is administered with dexamethasone, 4 mg twice daily, starting 24 h before drug infusion to diminish hepatic toxicity.

Renal adjustment

Consult product literature in severe impairment

Hepatic adjustment

Caution in mild to moderate impairment; avoid in severe impairment. Dose reduction according to bilirubin concentration.

• Pregnancy (teratogenic and toxic in animal studies)
• Severe hepatic impairment
• Conception during treatment and for at least 6 months after treatment (men or women)