TRABEC (TRABECTEDIN) POWDER FOR SOLN 1MG VIAL

Trabectedin (originally derived from the sea squirt Ecteinascidia turbinata) is an antineoplastic medicine that works by binding to the minor groove of DNA, bending it towards the major groove, and disrupting the transcription machinery — particularly inhibiting RNA polymerase II and various transcription factors.

This ultimately triggers apoptosis (programmed cell death) in rapidly dividing cancer cells.

Trabectedin is used to treat adults with:

•       Advanced soft tissue sarcoma (STS) — after failure of anthracyclines and ifosfamide, or patients who are unsuitable for these agents.

•       Relapsed platinum-sensitive ovarian cancer — in combination with pegylated liposomal doxorubicin (PLD).

Trabectedin is administered exclusively in a hospital oncology setting by trained healthcare professionals. It is given as a slow intravenous infusion over 24 hours, via a central venous catheter (PICC line or central line) — peripheral venous access is not acceptable due to the risk of severe vesicant damage if extravasation occurs.

Dose: 1.5 mg/m2 (soft tissue sarcoma monotherapy) or 1.1 mg/m2 (in combination with PLD for ovarian cancer), given every 3 weeks. Premedication with dexamethasone 20 mg IV is mandatory before each infusion (hepatoprotective and anti-emetic effect).

•       Strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, clarithromycin): significantly increase trabectedin exposure — avoid concomitant use.

•       Strong CYP3A4 inducers (rifampicin, phenytoin, carbamazepine, St John's Wort): reduce trabectedin levels — avoid.

•       Alcohol: increases hepatotoxicity risk — avoid on the day of infusion and for several days after.

•       Hepatotoxic drugs: additive liver toxicity risk — use with caution.

Store below 25°C. Protect from light. Reconstitute with sterile water for injection (20 mL per 1 mg vial). Dilute further in sodium chloride 0.9% or glucose 5% in a PVC-free container. The diluted solution (in glass or polyolefin infusion bags) is stable for 30 hours at room temperature. Must be administered within this window via a 0.2 mcm in-line filter.

Each trabectedin infusion takes 24 hours in hospital. You will be connected to a drip through your central line and will need to stay comfortable for the full infusion. Anti-emetic medicines are given before the infusion starts to prevent nausea, and dexamethasone is given to protect the liver.

Liver enzyme elevations are very common and are usually transient — they typically rise in the first week after infusion and return to normal before the next cycle. Your blood liver tests will be checked before every treatment cycle.

Report any severe muscle pain, weakness, or very dark urine immediately — these could indicate rhabdomyolysis (muscle breakdown), which is a rare but serious complication.

Trabectedin dose is calculated per body surface area (BSA). The standard dose of 1.5 mg/m2 Q3W for STS means a typical 1.73 m2 patient receives approximately 2.6 mg — requiring 3 vials. The 1 mg vial size is therefore the standard dispensing unit.

Hepatotoxicity monitoring: ALT/AST/bilirubin/alkaline phosphatase and CK and total bilirubin before each cycle. Hold if ALT/AST >2.5 x ULN, ALP >2.5 x ULN (>5 x ULN if liver/bone involvement), bilirubin >ULN, or CK >2.5 x ULN.

Mandatory dexamethasone premedication has both hepatoprotective and anti-emetic utility — do not reduce or omit. CYP3A4 interactions are clinically significant — always screen medications. Avoid concomitant alcohol for at least 48 hours post-infusion.

Why does the infusion take 24 hours?

Trabectedin must be given slowly to minimise liver toxicity and other side effects. The 24-hour administration schedule was determined in clinical trials to be the optimal balance of efficacy and tolerability.

Why is dexamethasone given before the infusion?

Dexamethasone at 20 mg provides significant hepatoprotection (reduces trabectedin-related liver enzyme elevation) and powerful anti-nausea effect. It is mandatory and must not be omitted or the dose reduced without specialist guidance.

Can I drink alcohol around the time of my infusion?

No — alcohol significantly increases the risk of liver damage when combined with trabectedin. Avoid alcohol from the day before the infusion until at least 48 hours after it is completed.

Can trabectedin cure my cancer?

Trabectedin is used for advanced cancers where cure is generally not achievable. The goal is to control the cancer, prolong life, and maintain quality of life for as long as possible. Many patients achieve months to years of disease control.