Trabectedin (Yondelis) is an alkylating agent indicated for the treatment of specific types of soft tissue sarcoma. It is used in adult patients with unresectable or metastatic liposarcoma or leiomyosarcoma whose disease has progressed following prior anthracycline-containing chemotherapy regimens.

Dosage and Administration, Recommended Dose of Trabectedin (Yondelis)

Routine Dosing Regimen

The standard recommended dose of trabectedin is 1.5 mg per square meter of body surface area, administered as a continuous intravenous infusion via a central venous catheter over 24 hours.

The treatment cycle is repeated every 3 weeks until disease progression or intolerable toxicities occur.

Important Premedication

Thirty minutes before each trabectedin infusion, 20 mg of dexamethasone should be administered intravenously as premedication to reduce the risk of certain adverse reactions.

Patient Eligibility Criteria for Dose Application

The recommended dose applies to patients with normal serum bilirubin levels and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels not exceeding 2.5 times the upper limit of normal (ULN).

No recommended dose has been established for patients with serum bilirubin levels above the upper limit of normal.

Dose Adjustment of Trabectedin (Yondelis)

Conditions Requiring Dose Delay

Platelet count below 100,000/μL.

Absolute neutrophil count (ANC) below 1,500/μL.

Total bilirubin above the upper limit of normal.

Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) above 2.5 times the upper limit of normal.

Alkaline phosphatase above 2.5 times the upper limit of normal.

Conditions Requiring Dose Reduction

Platelet count below 25,000/μL.

Absolute neutrophil count (ANC) below 1,000/μL accompanied by fever or infection, or ANC below 500/μL persisting for more than 5 days.

Total bilirubin above the upper limit of normal.

Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) above 5 times the upper limit of normal.

Creatine phosphokinase (CPK) above 5 times the upper limit of normal.

Conditions Requiring Permanent Discontinuation

Persistent adverse reactions resulting in dose delay exceeding 3 weeks.

Need for further dose reduction after the dose has already been lowered to 1.0 mg per square meter of body surface area.

Occurrence of rhabdomyolysis.

Administration in Special Populations

Patients with Hepatic Impairment

The pharmacokinetics of trabectedin have not been studied in patients with total bilirubin levels above the upper limit of normal.

For such patients, it is recommended to avoid use or evaluate the risk-benefit ratio with extreme caution, along with enhanced monitoring of liver function.

Patients with Renal Impairment

Dose adjustment is not recommended for patients with mild to moderate renal impairment.

The pharmacokinetics in patients with severe renal impairment or end-stage renal disease have not been clearly established, and cautious use is required.

Pregnant and Lactating Women

Based on its mechanism of action, trabectedin may cause potential harm to the fetus and is contraindicated during pregnancy.

Women of childbearing potential should use effective contraceptive measures during treatment and for at least 2 months after the last dose.

Lactating women should discontinue breastfeeding during treatment.