- Brand name: Zepzelca
- Class: Antineoplastic agent – synthetic analog of trabectedin (marine-derived alkaloid)
- Mechanism of action:
- Binds to DNA at guanine residues in the minor groove.
- Causes double-strand breaks and inhibition of transcription.
- Induces apoptosis of cancer cells.
- Also reduces tumor-associated macrophages, decreasing pro-tumor inflammation.
Indications (FDA-approved)
- Metastatic small cell lung cancer (SCLC) → in adults with disease progression on or after platinum-based chemotherapy.
- Investigated in: mesothelioma, Ewing sarcoma, ovarian cancer (not standard).
Dosing (Adults)
- 3.2 mg/m² IV infusion over 60 minutes every 21 days
- Continue until disease progression or unacceptable toxicity.
Renal/Hepatic considerations:
- Avoid in moderate/severe hepatic impairment (AST/ALT >3× ULN or bilirubin >1.5× ULN).
- No dose adjustment for mild renal impairment; limited data for severe renal impairment.
Adverse Effects
Common (≥20%):
- Myelosuppression: neutropenia, anemia, thrombocytopenia
- Fatigue
- Nausea, vomiting, constipation, decreased appetite
- Increased creatinine, ALT, AST
Serious:
- Febrile neutropenia
- Hepatotoxicity
- Rhabdomyolysis (rare)
Monitoring
- CBC with differential (baseline and prior to each cycle)
- Liver function tests
- Renal function (creatinine, CPK if muscle symptoms)
- Infection/fever signs
Supportive Care
- Antiemetics (moderately emetogenic)
- Growth factor support (G-CSF) for high-risk neutropenia
- Antimicrobial prophylaxis not routinely required but may be considered in prolonged neutropenia
Key Point for Oncology Pharmacists:
- Lurbinectedin is now a second-line standard option for relapsed SCLC, especially for patients progressing after platinum-etoposide.
- Compared with topotecan (older standard), it shows a favorable safety profile with less severe hematologic toxicity.