Trabectedin

Non-platinum based Alkylating Agents

MECHANISM OF ACTION

Trabectedin is a marine-derived compound (alkylating agent) which blocks the cell cycle at the G2/M phase by covalently binding to the minor DNA groove, bending the helix toward the major groove and altering DNA transcription . Affects activity of DNA binding proteins, transcription factors and DNA repair mechanism, leading to cell death.

Elimination :
Feces (58%; only negligible amounts as unchanged drug); urine (6%; only negligible amounts as unchanged drug)

MECHANISM OF KIDNEY INJURY

ATN (Acute tubular necrosis), Rhabdomyolysis , CPK elevation ,Isolated increase in Serum Cr is noted without AKI phenotype

CLINICAL KIDNEY SYNDROME

Pseudo AKI (false elevation in Cr), Rhabdomyolysis, Hypotension, Anasarca

CARDIOVASCULAR ADVERSE EFFECTS

LYTE ABNORMALITIES

Hypoalbuminemia, elevated Cr , increased CPK, bone marrow suppression , AST/alt/alkphos/ Bil elevation

RISK FACTORS

Prior to each treatment cycle, ANC should be ≥1,500/mm3, platelets ≥100,000/mm3 total bilirubin ≤ ULN, and alkaline phosphatase, ALT, AST, and CPK ≤2.5 times ULN.
Recommended dose reduction levels in patients with mild or moderate hepatic impairment at baseline. Monitor CPK levels prior to each dose

MITIGATION STRATEGIES

Monitor CPK levels prior to each dose. Creatine phosphokinase (CPK) elevations occurred in nearly one-third of patients receiving trabectedin

SUGGESTIONS

Discontinue offending drug, check CPK, Liver function tests

NOTES/COMMENTS

PHARMACOKINETICS

Molecular Weight

Volume of Distribution

Plasma Protein Binding

Metabolism

Bioavailability

Half-life elimination

Time to peak

Excretion

Dialyzable?

REF:

PMID 20015930, 17611408, 11234874, 14990645, 21617727

PATHOLOGY SLIDES:

ENTRY UPDATES:

Kartik Kalra

United States

Sep 25, 2022

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