Trabectedin STADA (Trabectedin)

What Is Trabectedin STADA and What Is It Used For?

Trabectedin STADA contains the active substance trabectedin, a marine-derived antineoplastic agent that works by binding to DNA and preventing tumor cells from multiplying. It is approved for the treatment of advanced soft tissue sarcoma and recurrent ovarian cancer.

Trabectedin is a unique anticancer drug originally derived from the Caribbean sea squirt Ecteinascidia turbinata, now produced synthetically. It belongs to the class of antineoplastic agents and works through a novel mechanism of action: it binds to the minor groove of the DNA double helix, bending it toward the major groove. This disrupts cellular processes essential for cancer cell survival, including transcription, DNA repair mechanisms, and cell division.

Unlike many conventional chemotherapy drugs that simply damage DNA, trabectedin has a more complex mode of action. It affects several pathways simultaneously, including interactions with transcription factors, interference with nucleotide excision repair (NER), and modulation of the tumor microenvironment. Trabectedin also depletes tumor-associated macrophages and reduces pro-inflammatory cytokines within the tumor, contributing to its anticancer activity. This multi-targeted approach makes it effective even in certain tumors that have developed resistance to other chemotherapy agents.

Trabectedin STADA is a generic version of the originator product Yondelis. It contains the same active substance in the same dosage form and has been shown to be bioequivalent to the reference product, meaning clinical outcomes are expected to be comparable when used in line with the approved prescribing information.

Approved Indications

Soft Tissue Sarcoma (STS): Trabectedin STADA is used as monotherapy for the treatment of adults with advanced soft tissue sarcoma after failure of anthracyclines and ifosfamide, or in patients who are unsuitable to receive these agents. Soft tissue sarcomas are a diverse group of malignant tumors arising from mesenchymal tissues including muscle, fat, blood vessels, nerves, tendons, and cartilage. They account for approximately 1% of adult malignancies, with more than 50 histological subtypes identified. Trabectedin has demonstrated particular activity in leiomyosarcoma and translocation-related sarcomas such as myxoid/round cell liposarcoma.

Ovarian Cancer: Trabectedin STADA is used in combination with pegylated liposomal doxorubicin (PLD) for the treatment of patients with relapsed platinum-sensitive ovarian cancer. This indication applies to patients whose cancer has returned after at least one prior platinum-based chemotherapy regimen. The combination therapy has demonstrated improved progression-free survival compared with PLD alone in the pivotal OVA-301 randomized trial, providing an important non-platinum option for patients.

The European Medicines Agency (EMA) first authorized trabectedin (as Yondelis) in 2007 for soft tissue sarcoma and in 2009 for ovarian cancer. Trabectedin STADA is a generic version produced by STADA Arzneimittel AG and follows the same approved indications as the reference product.

How Trabectedin Works (Mechanism of Action)

At the molecular level, trabectedin alkylates guanine residues in the DNA minor groove, bending the DNA helix toward the major groove. This distortion interferes with multiple cellular processes:

• Transcription interference: Trabectedin inhibits the binding of several transcription factors to DNA, blocking the expression of genes needed for tumor cell survival.
• DNA repair paradox: Unlike many chemotherapy agents, trabectedin actually requires active nucleotide excision repair (NER) for its cytotoxicity. Tumor cells with functional NER pathways are therefore particularly sensitive.
• Cell cycle disruption: Exposure to trabectedin triggers G2/M cell cycle arrest and ultimately apoptosis (programmed cell death).
• Tumor microenvironment effects: Trabectedin reduces the number of tumor-associated macrophages and lowers inflammatory cytokines (e.g., CCL2, IL-6) that can promote tumor growth and immune evasion.

What Should You Know Before Taking Trabectedin STADA?

Before starting Trabectedin STADA, your doctor must assess your liver and kidney function, heart health, and blood counts. The drug is contraindicated in patients with serious infections, those who are breastfeeding, and those receiving yellow fever vaccination.

Because trabectedin is a potent cytotoxic drug with a narrow therapeutic index, a thorough pre-treatment evaluation is essential. Your oncologist will review your medical history, perform a physical examination, and order laboratory tests to ensure that your organs can tolerate chemotherapy. These baseline assessments are also used for comparison during treatment so that toxicity can be detected early.

Contraindications

Trabectedin STADA must not be used in the following situations:

• Hypersensitivity to trabectedin or any of the excipients (sucrose, potassium dihydrogen phosphate, phosphoric acid, potassium hydroxide)
• Serious active infection – systemic or localized infections must be treated and resolved before starting therapy
• Breastfeeding – trabectedin may pass into breast milk and cause harm to the nursing infant
• Yellow fever vaccination – concurrent administration with live vaccines is contraindicated due to the risk of fatal systemic vaccine disease in immunocompromised patients

Warnings and Precautions

Trabectedin STADA or its combination with PLD should not be used if you have severe liver, kidney, or cardiac impairment. Before and during treatment, inform your physician if you have or have had any of the following conditions:

• Liver disease or abnormal liver function tests
• Kidney problems or reduced renal function
• Heart disease or a history of cardiovascular problems
• Left ventricular ejection fraction (LVEF) below the lower limit of normal
• Previous treatment with high-dose trabectedin
• History of muscle disorders or unexplained muscle pain

Routine laboratory monitoring during treatment typically includes complete blood count (CBC), liver function tests (ALT, AST, bilirubin, alkaline phosphatase), renal function (creatinine), and creatine phosphokinase (CPK) prior to each infusion. Cardiac function (echocardiogram or MUGA scan) is usually assessed at baseline and periodically thereafter, especially in patients receiving trabectedin in combination with PLD.

Trabectedin STADA should not be given to children and adolescents under 18 years of age for pediatric sarcomas, as safety and efficacy have not been established in this population. Use in children is limited to clinical trial settings under specialist supervision.

Pregnancy and Breastfeeding

Trabectedin STADA carries significant reproductive risks. Based on its mechanism of action, trabectedin may cause genetic damage (genotoxicity) and harm to the developing fetus. The following precautions are essential:

• Pregnancy: Trabectedin must not be used during pregnancy. If you become pregnant during treatment, inform your doctor immediately. Genetic counseling is recommended due to the potential for genetic damage.
• Women of childbearing potential: Must use highly effective contraception during treatment and for at least 3 months after the final dose.
• Men: Must use effective contraception during treatment and for at least 5 months after the final dose, as trabectedin may cause chromosomal damage in sperm.
• Breastfeeding: You must stop breastfeeding before starting treatment and not resume until your physician confirms it is safe to do so.
• Fertility preservation: Patients should receive counseling about egg or sperm cryopreservation before starting treatment, as trabectedin may cause permanent infertility.
• Genetic counseling: Recommended for patients who wish to have children after completing treatment.

Driving and Operating Machinery

Trabectedin treatment commonly causes fatigue, weakness, and occasionally dizziness. You should not drive or operate heavy machinery if you experience these side effects. Discuss your ability to perform these activities with your healthcare team, particularly in the first days after each infusion when fatigue tends to peak.

Excipients

Trabectedin STADA contains less than 1 mmol (39 mg) of potassium per vial, making it essentially potassium-free. This is generally not a concern for patients on potassium-restricted diets. The product contains no preservatives and must be reconstituted immediately prior to use.

How Does Trabectedin STADA Interact with Other Drugs?

Trabectedin is metabolized primarily by the CYP3A4 enzyme system. Drugs that inhibit or induce CYP3A4 can significantly alter trabectedin blood levels. Concurrent use with hepatotoxic or myotoxic drugs may increase the risk of liver damage or rhabdomyolysis.

Trabectedin undergoes extensive hepatic metabolism, primarily through the cytochrome P450 3A4 (CYP3A4) enzyme pathway. This makes it susceptible to pharmacokinetic interactions with drugs that affect this enzyme system. Additionally, the inherent hepatotoxicity and potential for muscle damage associated with trabectedin mean that co-administration with drugs sharing similar toxicity profiles requires careful monitoring.

Before starting Trabectedin STADA, provide your oncologist with a complete list of all prescription medicines, over-the-counter drugs, vitamins, and herbal supplements you are taking. Do not start or stop any medication during treatment without consulting your treatment team.

Major Interactions

The following drugs should be avoided or require close monitoring when used with trabectedin:

Minor Interactions

The following drugs may alter trabectedin levels or share overlapping toxicity and require monitoring:

What Is the Correct Dosage of Trabectedin STADA?

Trabectedin STADA is administered intravenously under specialist supervision. The dose is calculated based on body surface area (BSA). For soft tissue sarcoma, the standard dose is 1.5 mg/m² given over 24 hours every 3 weeks. For ovarian cancer, the dose is 1.1 mg/m² given over 3 hours (after PLD) every 3 weeks.

Trabectedin STADA must be administered exclusively in a hospital setting by healthcare professionals experienced in the use of chemotherapy. The drug is given as an intravenous infusion, preferably through a central venous catheter to minimize the risk of extravasation. Before each administration, your oncologist will assess your clinical condition and laboratory values to determine whether treatment can proceed and whether dose adjustments are necessary.

The 0.25 mg vials are typically used for careful dose titration, for patients requiring lower total doses (e.g., based on reduced body surface area or dose reductions due to toxicity), and in pediatric clinical trial settings. The exact number of vials per infusion is calculated by the hospital pharmacy based on the individual's BSA and prescribed dose.

Adults – Soft Tissue Sarcoma

Adults – Ovarian Cancer (Combination with PLD)

Children and Adolescents

Trabectedin STADA is not recommended for use in patients under 18 years of age with pediatric sarcomas. The safety and efficacy of trabectedin in the pediatric population have not been established, and no dosage recommendation can be made outside of approved clinical trials.

Elderly Patients

No specific dose adjustment is required based on age alone. However, elderly patients may be more susceptible to adverse effects, particularly hepatotoxicity, myelosuppression, and fatigue, and may require more frequent monitoring. Dose adjustments are guided by organ function and tolerability rather than chronological age. In clinical studies, efficacy in patients older than 65 years appeared similar to that in younger patients, although toxicity rates tended to be slightly higher.

Dose Adjustments

Your oncologist will monitor you closely throughout treatment and may adjust your dose based on:

• Liver function: Elevated transaminases or bilirubin may require dose reduction or treatment delay
• Blood counts: Neutropenia (low white blood cells) or thrombocytopenia (low platelets) may necessitate dose modifications
• Kidney function: Dose adjustments may be needed for moderate renal impairment; use in severe renal impairment is not recommended
• Creatine phosphokinase (CPK) levels: Elevated CPK may indicate muscle damage and require dose reduction or discontinuation
• Overall tolerability: Treatment delays or dose reductions are common to manage side effects

Typical dose levels in the event of significant toxicity are 1.2 mg/m² (first reduction) and 1.0 mg/m² (second reduction) for soft tissue sarcoma. Patients who cannot tolerate the reduced dose should have treatment discontinued.

Missed Dose

Since trabectedin is administered in a clinical setting every 3 weeks, missed doses are managed by your treatment team. If a scheduled treatment is delayed (e.g., due to abnormal blood results or unresolved side effects), your oncologist will determine the appropriate time to resume treatment. Do not attempt to make up for a missed dose by taking extra medication. Cycle delays of up to 3 weeks are generally considered acceptable, but prolonged delays may indicate that treatment should be permanently stopped.

Overdose

As trabectedin is administered by healthcare professionals in a controlled setting, accidental overdose is unlikely but has been reported in clinical trials. There is no specific antidote for trabectedin overdose. Treatment is supportive and may include:

• Intensive monitoring of vital signs, liver function, blood counts, and muscle enzymes
• Administration of granulocyte colony-stimulating factor (G-CSF) for severe neutropenia
• Supportive care for any organ toxicity that develops, including intensive care unit admission if needed
• Aggressive hydration and electrolyte correction to manage potential rhabdomyolysis

What Are the Side Effects of Trabectedin STADA?

Like all chemotherapy medications, Trabectedin STADA can cause side effects, though not everyone experiences them. The most common side effects include fatigue, nausea, vomiting, loss of appetite, changes in blood counts, and elevated liver enzymes. Some side effects can be serious and require immediate medical attention.

The side effects listed below are based on clinical trial data and post-marketing surveillance of trabectedin. The frequency classifications follow international conventions: very common (>1/10), common (1/10 to 1/100), uncommon (1/100 to 1/1,000), and rare (<1/1,000). Your healthcare team will monitor you closely for these effects and can provide treatments to manage many of them, including anti-emetics, G-CSF, transfusions, and dose adjustments.

Serious Side Effects

The following side effects are potentially serious and require prompt medical evaluation:

Other Side Effects

How Should You Store Trabectedin STADA?

Trabectedin STADA vials must be stored in a refrigerator at 2°C to 8°C (36°F to 46°F). Keep the medication out of the sight and reach of children. Do not use after the expiration date printed on the carton and vial label.

Proper storage of Trabectedin STADA is essential to maintain its stability and efficacy. As a cytotoxic agent, it also requires specific handling and disposal procedures that are typically managed by hospital pharmacy staff rather than patients:

• Unopened vials: Store in a refrigerator at 2°C to 8°C. Protect from light and keep in the original carton.
• Do not freeze: Freezing can damage the product.
• After reconstitution: Chemical and physical stability has been demonstrated for 30 hours at temperatures between 20°C and 25°C, as well as at 2°C to 8°C. From a microbiological standpoint, the reconstituted solution should be diluted and used immediately, or within 24 hours if stored at 2°C to 8°C under validated aseptic conditions.
• After dilution: Chemical and physical stability has been demonstrated for 30 hours at up to 25°C. Use immediately from a microbiological perspective.
• Visual inspection: Do not use if visible particles are observed after reconstitution or dilution, or if the solution appears unusually cloudy or discolored.
• Disposal: Unused product and waste material must be disposed of in accordance with local requirements for cytotoxic medications. Do not dispose of via household waste or wastewater.

Safe Handling

Trabectedin STADA is a cytotoxic drug. Healthcare professionals handling the product should follow institutional guidelines for safe preparation and administration of chemotherapy, including use of personal protective equipment (gloves, gowns, eye protection), dedicated biosafety cabinets for reconstitution, and closed-system transfer devices where available. Accidental skin contact should be washed immediately with copious amounts of soap and water; eye contact should be managed by prolonged rinsing with water and urgent medical evaluation.

What Does Trabectedin STADA Contain?

Each vial of Trabectedin STADA 0.25 mg contains trabectedin as the active ingredient along with sucrose, potassium dihydrogen phosphate, phosphoric acid, and potassium hydroxide as excipients.

Active Ingredient

• Trabectedin STADA 0.25 mg: Each vial contains 0.25 mg of trabectedin. After reconstitution with 5 mL of sterile water for injections, each mL of the resulting solution contains 0.05 mg of trabectedin.

Inactive Ingredients (Excipients)

• Sucrose (bulking agent and lyoprotectant that stabilizes trabectedin during freeze-drying)
• Potassium dihydrogen phosphate (buffer to maintain pH)
• Phosphoric acid (for pH adjustment)
• Potassium hydroxide (for pH adjustment)

Appearance and Packaging

Trabectedin STADA is supplied as a white to off-white powder for concentrate for solution for infusion. It is provided in type I glass vials with a rubber stopper and aluminium seal. Each outer carton contains one vial with 0.25 mg of trabectedin. After reconstitution with 5 mL of sterile water for injections, the solution should be clear, colorless to slightly yellowish, and essentially free from visible particles. The reconstituted solution is subsequently diluted in 500 mL of 0.9% sodium chloride or 5% glucose before intravenous administration.

Marketing Authorization

Trabectedin STADA is manufactured and marketed by STADA Arzneimittel AG, headquartered in Bad Vilbel, Germany. STADA is one of Europe's leading generic and consumer healthcare companies, with authorization to supply trabectedin across the European Economic Area under a decentralized procedure. The product contains the same active substance (trabectedin) as the originator product Yondelis and is bioequivalent within accepted regulatory limits.

Frequently Asked Questions About Trabectedin STADA