General Information

Yondelis (trabectedin) is an alkylating agent.

Yondelis is specifically indicated for the treatment of patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-containing regimen.

Yondelis is supplied as an injection for intravenous administration. The recommended dose is 1.5 mg/m2 administered as an intravenous infusion over 24 hours through a central venous line every 21 days (3 weeks), until disease progression or unacceptable toxicity, in patients with normal bilirubin and AST or ALT less than or equal to 2.5 times the upper limit of normal. There is no recommended dose of Yondelis in patients with serum bilirubin levels above the institutional upper limit of normal.

Mechanism of Action

Yondelis (trabectedin) is an alkylating drug that binds guanine residues in the minor groove of DNA, forming adducts and resulting in a bending of the DNA helix towards the major groove. Adduct formation triggers a cascade of events that can affect the subsequent activity of DNA binding proteins, including some transcription factors, and DNA repair pathways, resulting in perturbation of the cell cycle and eventual cell death.

Side Effects

Adverse effects associated with the use of Yondelis may include, but are not limited to, the following:

• nausea
• fatigue
• vomiting
• constipation
• decreased appetite
• diarrhea
• peripheral edema
• dyspnea
• headache
• neutropenia
• increased ALT
• thrombocytopenia
• anemia
• increased AST
• increased creatine phosphokinase

Clinical Trial Results

The FDA approval of Yondelis was based on a randomized (2:1), open-label, active-controlled trial comparing treatment with YONDELIS 1.5 mg/m2 as a 24-hour continuous intravenous infusion once every 3 weeks to dacarbazine 1000 mg/m2 intravenous infusion (20 to 120 minutes) once every 3 weeks. Treatment continued in both arms until disease progression or unacceptable toxicity. The trial enrolled 518 subjects with unresectable, locally advanced or metastatic leiomyosarcoma or liposarcoma (dedifferentiated, myxoid round cell, or pleomorphic) and previous treatment with an anthracycline- and ifosfamide-containing regimen or an anthracycline-containing regimen and one additional cytotoxic chemotherapy regimen. Subjects receiving Yondelis experienced a delay in the growth of their tumor (progression-free survival), which occurred on average about 4.2 months after starting treatment, compared to participants assigned to dacarbazine, whose disease progressed an average of 1.5 months after starting treatment.