Trabectedin (Yondelis)

Approved for the treatment of patients with unresectable metastatic soft tissue sarcoma, liposarcoma and leiomyosarcoma.

Derived from the sea squirt.

Affects multiple key processes in tumor cell replication and death and targets the tumor microenvironment.

Indicated for patients with Soft tissue sarcomas who previously received chemotherapy that contained anthracyclines.

Overall response rate in soft tissue sarcomas is 10%.
When used in combination with specified radiotherapy Increased response rates in soft tissue sarcomas.

Intravenous agent.

Protein binding ,of 94 to 98%.

Mostly CYP3A4-mediated hepatic metabolism.

Biological half-life 180 hours

Excretion mostly fecal

Brand name Yondelis.

It is approved for use in advanced soft tissue sarcoma and ovarian cancer.

Clinical efficacy data was mainly based on patients with liposarcoma and leiomyosarcoma.

Patients must have received prior chemotherapy with an anthracycline to receive this agent.

Blocks DNA binding of the oncogenic transcription factor FUS-CHOP and reverses the transcriptional program in myxoid liposarcoma.

Trabectedin promotes differentiation and reverses the oncogenic phenotype in these cells byreversing the genetic program created by this transcription factor,

Mechanism of action is complex and not completely understood, other than transcriptional interference,

Binds and alkylates DNA at the N2 position of guanine.

It is known from in-vitro work that this binding occurs in the minor groove, spans approximately 3 to 5 bp and is most efficient with CGG sequences.

Interferes directly with activated transcription, poisons the transcription-coupled nucleotide excision repair (TCR) complex, promotes degradation of RNA polymerase II, and generates DNA double-strand breaks.

Compared with dacarbazine randomized patients with metastatic or recurrent leiomyosarcoma or liposarcoma there was a progression free survival 4.2 months versus 1.5 months for dacarbazine In a phase 3 trial.

Most common adverse events are: Nausea and fatigue, vomiting, diarrhea, constipation, impaired appetite, dyspnea, headache, edema, neutropenia, thrombocytopenia, anemia, elevated liver functions, and hypoalbuminemia.

Can cause significant hepatotoxicity and even liver failure.

Can cause significant neutropenia and sepsis.

May be associated with cardiomyopathy.

Extravasation can lead to tissue necrosis.

Can cause rhabdomyolysis and musculoskeletal toxicity.

The use of strong CYP3A inhibitors and grapefruit should be avoided.

Dosage is 1.5 mg/m² administered as an IV infusion over 24 hours through a central venous line every 21 days, until disease progression or unacceptable toxicity occurs.

Dexamethasone 20 mg IV is given 30 minutes prior to each dose.

Leave a Reply

Your email address will not be published. Required fields are marked *