lurbinectedin

Action and Spectrum

Actions and Spectrum: 

Actions: 

lurbinectedin acts as a selective inhibitor of RNA polymerase II, an enzyme involved in transcription. By inhibiting RNA polymerase II, lurbinectedin disrupts the transcription of genes critical for tumor cell survival and proliferation. lurbinectedin causes DNA damage by forming covalent adducts with DNA.

This leads to the formation of DNA-protein cross-links and DNA strand breaks, resulting in DNA damage within tumor cells. The inhibition of transcription and induction of DNA damage by lurbinectedin collectively contribute to its antiproliferative effects. It intrudes with the ability of cancer cells to replicate and divide, ultimately inhibiting tumor growth. 

Spectrum: 

lurbinectedin has shown efficacy in treating relapsed or refractory small-cell lung cancer, a highly aggressive and often challenging-to-treat form of lung cancer. 

lurbinectedin has also demonstrated activity in metastatic triple-negative breast cancer, a subtype lacking estrogen receptors, progesterone receptors, and HER2/neu amplification. TNBC is often associated with a poorer prognosis and limited treatment options. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Decreased hemoglobin (74%) 

Decreased leukocytes (79%) 

Decreased neutrophils (71%) 

Decreased lymphocytes (79%) 

Fatigue (77%) 

Increased creatinine (69%) 

Nausea (37%) 

Musculoskeletal pain (33%) 

Increased ALT (66%) 

Increased glucose (52%) 

Decreased platelets (37%) 

Decreased appetite (33%) 

Decreased albumin (32%) 

Dyspnea (31%) 

Decreased magnesium (22%) 

Vomiting (22%) 

Constipation (31%) 

Decreased sodium (31%) 

Increased AST (26%) 

Cough (20%) 

Abdominal pain (11%) 

Peripheral neuropathy (11%) 

Diarrhea (20%) 

Respiratory tract infection (18%) 

Pyrexia (13%) 

1-10% 

Decreased hemoglobin (10%) 

Decreased platelets (7%) 

Dyspnea (6%) 

Respiratory tract infection (5%) 

Pneumonia (7%) 

Decreased sodium (7%) 

Increased glucose (5%) 

Diarrhea (4%) 

Increased AST (2%) 

Musculoskeletal pain (4%) 

Increased ALT (4%) 

Abdominal pain (1%) 

Decreased appetite (1%) 

Decreased albumin (1%) 

Headache (1%) 

Peripheral neuropathy (1%) 

Black Box Warning

Black Box Warning: 

None  

Contraindication / Caution

Contraindication/Caution: 

Contraindications 

• Hypersensitivity 
• Active pathological bleeding 

Cautions 

• Gastrointestinal effects 
• Renal impairment 
• Hepatic impairment 
• Drug interactions 
• Cardiac effects 

Pregnancy / Lactation

Pregnancy consideration:  

No data is available regarding the risk due to drugs in pregnant females. Though administering the drug  

Breastfeeding warnings:  

No data is available regarding the excretion of drug in breast milk. 

Pregnancy category: 

Category A: well-controlled and satisfactory studies show no risk to the fetus in the first or later trimester. 

<b>Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: No data is available for the drug under this category. 

Pharmacology

Pharmacology: 

lurbinectedin selectively binds to the DNA minor groove, leading to the displacement of specific DNA-binding proteins. This interaction interferes with the activity of RNA polymerase II, a key enzyme involved in transcription. By inhibiting transcription, lurbinectedin disrupts the expression of genes critical for tumor cell survival and proliferation. 

Pharmacodynamics: 

lurbinectedin also induces DNA damage within tumor cells. It forms covalent adducts with DNA, resulting in the formation of DNA-protein cross-links and DNA strand breaks. These DNA lesions contribute to the anti-tumor effects of lurbinectedin.  

Pharmacokinetics: 

Absorption 

The peak plasma concentration is 107 mcg/mL 

The area under the curve is 551 mcg⋅hr/L  

Distribution 

Protein-bound is 99% 

The volume of distribution of lurbinectedin at steady state is 504 L 

Metabolism 

The CYP3A4 enzyme majorly metabolizes the drug. 

Elimination and Excretion 

The half-life is 51 hours 

The rate of clearance is 89% 

The drug is excreted 89% in feces and 6% in urine. 

Adminstartion

Administration: 

lurbinectedin is administered as an intravenous infusion over a specified duration. The infusion is typically given through a vein in the arm or a central venous catheter.

The infusion rate and duration may vary depending on the specific indication and treatment protocol the healthcare provider prescribes. Following the recommended infusion rate and duration is essential to ensure proper medication delivery. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: lurbinectedin 

Pronounced: LOOR-bin-EK-te-din 

Why do we use lurbinectedin? 

lurbinectedin is approved for treating metastatic small-cell lung cancer in patients who have previously received platinum-based chemotherapy. It is used when the disease gets progresses or relapses after initial treatment. 

lurbinectedin is indicated for treating metastatic triple-negative breast cancer in patients who received at least two lines before chemotherapy for metastatic disease.