Trabectedin (Yondelis) is an alkylating agent approved by the U.S. FDA in 2015 for the treatment of patients with unresectable or metastatic liposarcoma or leiomyosarcoma who have previously received anthracycline-containing therapy. As a fixed-dose combination of xanomeline and trospium chloride, it can improve symptoms while also posing risks across multiple systems, requiring strict clinical monitoring.

What Are the Side Effects of Trabectedin (Yondelis)?

Common Side Effects

Gastrointestinal Reactions: Nausea (75%), vomiting (46%), constipation (37%), diarrhea (35%).

Systemic Reactions: Fatigue (69%), peripheral edema (28%).

Metabolic and Nutritional Disorders: Decreased appetite (37%).

Respiratory Abnormalities: Dyspnea (25%).

Neurological Symptoms: Headache (25%).

Abnormal Laboratory Findings

Neutropenia (43%).

Increased ALT (31%).

Thrombocytopenia (21%).

Anemia (19%).

Increased AST (17%).

Warnings for Severe Side Effects of Trabectedin (Yondelis)

Neutropenic Sepsis

Incidence: Grade 3–4 neutropenia occurs in 43% of patients, and the incidence of neutropenic sepsis is 2.6%.

Risk Characteristics: Fatal cases may occur (incidence of 1.1% in clinical trials).

Monitoring Requirements: Monitor neutrophil count before each dose administration and regularly during the treatment cycle.

Management Measures: Suspend medication when neutrophils are < 1500/mcL.

Rhabdomyolysis

Clinical Manifestations: The incidence of elevated creatine phosphokinase (CPK) is 32%, with grade 3–4 elevation accounting for 6%.

Severe Consequences: May lead to renal failure; the mortality rate from rhabdomyolysis is 0.8%.

Monitoring Frequency: Evaluate CPK levels before each dose administration.

Hepatotoxic Reactions

Incidence: Grade 3–4 elevation of liver enzymes occurs in 35% of patients.

Special Warning: The incidence of drug-induced liver injury is 1.3%.

Dose Adjustment: Suspend medication when CPK is > 2.5 times the upper limit of normal.

Risk of Cardiomyopathy

High-Risk Factors: Left ventricular ejection fraction (LVEF) below the lower limit of normal, cumulative prior anthracycline dose ≥ 300 mg/m², age ≥ 65 years, and history of cardiovascular disease.

Monitoring Method: Assess LVEF via echocardiography before the start of treatment and every 2–3 months thereafter.

Precautions for Using Trabectedin (Yondelis)

Contraindicated Populations

Patients with a known severe allergy to trabectedin.

Patients with severe hepatic impairment.

Patients with urinary retention or gastric retention.

Patients with untreated angle-closure glaucoma.

Management of Drug Interactions

Strong CYP3A Inhibitors (e.g., ketoconazole): Concomitant use should be avoided.

Strong CYP3A Inducers (e.g., rifampicin): Concomitant use should be avoided.

Indications for Permanent Discontinuation

Persistent adverse reactions requiring dose administration delay for more than 3 weeks.

Need for further dose reduction after the dose has been reduced to 1.0 mg/m².

Development of capillary leak syndrome or rhabdomyolysis.

Occurrence of grade 3–4 cardiac adverse events or LVEF below the lower limit of normal.