trabectedin

Action and Spectrum

Actions and Spectrum 

trabectedin attaches to the DNA’s minor groove and creates covalent connections with the N2 position of the guanine residues.  

Transcription factors functions are disrupted by trabectedin, particularly those responsible for controlling the expression of genes important in cell growth and survival.  

A type of cancer that develops in fat cells, typically occurring in the limbs or abdomen. A malignant tumor usually affecting the soft tissues around the joints, especially in the extremities. 

Drug Interaction

Adverse Reaction

Frequency defined  

1-10% 

Fatigue, grades 3-4 (8%) 

Diarrhea, grades 3-4 (1.6%) 

Increased alkaline phosphatase, grades 3-4 (1.6%) 

Vomiting, grades 3-4 (6%)  

Dyspnea, grades 3-4 (4.2%)  

Hyperbilirubinemia, grades 3-4 (1.9%) 

Increased creatinine, grades 3-4 (4.2%) 

Decreased appetite, grades 3-4 (1.9%) 

Nausea, grades 3-4 (7%) 

Hypoalbuminemia, grades 3-4 (3.7%) 

Increased CPK, grades 3-4 (6.4%) 

<1% 

Headache, grades 3-4 

Insomnia, grades 3-4 

Constipation, grades 3-4 

Peripheral edema, grades 3-4 

>10%  

Constipation, all grades (37%) 

Diarrhea, all grades (35%)  

Myalgia, all grades (12%) 

Nausea, all grades (75%)  

Dyspnea, all grades (25%) 

Arthralgia, all grades (15%) 

Decreased appetite, all grades (37%) 

Insomnia, all grades (15%) 

Headache, all grades (25%) 

Vomiting, all grades (46%) 

Peripheral edema, all grades (28%) 

Fatigue, all grades (69%) 

Laboratory abnormalities 

Increased CPK, all grades (33%) 

Anemia, all grades (96%)   

Increased AST, grades 3-4 (17%) 

Hyperbilirubinemia, all grades (13%) 

Neutropenia, grades 3-4 (43%) 

Increased AST, all grades (84%)  

Neutropenia, all grades (66%) 

Anemia, grades 3-4 (19%) 

Increased creatinine, all grades (46%) 

Increased alkaline phosphatase, all grades (70%) 

Thrombocytopenia, grades 3-4 (21%) 

Increased ALT, grades 3-4 (31%) 

Increased ALT, all grades (90%) 

Hypoalbuminemia, all grades (63%) 

Thrombocytopenia, all grades (59%) 

Post marketing reports 

Mucosal inflammation at administration site 

Capillary leak syndrome 

Black Box Warning

Black Box Warning 

None

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• trabectedin is contraindicated in individuals with a known hypersensitivity or severe allergic reaction to trabectedin or any of its components.  

Caution: 

• trabectedin is primarily metabolized in the liver, so caution is advised in patients with pre-existing liver dysfunction.  
• trabectedin’s pharmacokinetics are not significantly affected by renal impairment, but caution is still recommended.  
• close monitoring of blood cell counts is essential before and during treatment.  
• Patients with pre-existing cardiac conditions or risk factors should be closely monitored during treatment. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excretion into human milk is unknown  

Pregnancy Categories:         

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: There is no data available for the drug under this category. 

Pharmacology

Pharmacology  

Covalent bonding impacts DNA-dependent processes like transcription and DNA repair by causing structural deformation of the DNA helix. The activity of multiple transcription factors is hampered by trabectedin. It affects the expression of genes involved in tumor growth and survival by preventing their binding to DNA. 

Pharmacodynamics 

trabectedin prevents the nucleotide excision repair (NER) pathway, which oversees fixing environmental-caused DNA damage, from working. trabectedin inhibits the NER pathway, preventing the repair of DNA lesions from occurring. 

trabectedin may affect the synthesis and activity of several cytokines, growth factors, and enzymes, which can influence the tumor microenvironment. It can influence the tumor cells and the immune system interaction as well as limit the release of pro-inflammatory mediators. 

Pharmacokinetics 

Absorption   

trabectedin is administered intravenously, resulting in immediate and complete bioavailability. After intravenous administration, trabectedin quickly distributes into the systemic circulation. 

Distribution 

trabectedin has a large volume of distribution, indicating extensive tissue distribution. It primarily binds to plasma proteins, with approximately 94% bound to albumin. 

Metabolism 

trabectedin undergoes significant liver enzymatic metabolization, primarily by the enzymes cytochrome P450 (CYP) 3A4 and CYP3A5.  

Elimination and excretion 

Hepatic metabolism and biliary excretion are the main routes through which trabectedin, and its metabolites are excreted. Renal excretion plays a minor role in the elimination process. 

Adminstartion

Administration  

trabectedin is administered as an intravenous infusion. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: trabectedin 

Why do we use trabectedin? 

trabectedin is primarily used for the treatment of certain types of soft tissue sarcomas.   

trabectedin is approved for the treatment of liposarcoma, which is a type of cancer that originates in fat cells.