Trabectedin Accord (Trabectedin)
Antineoplastic agent for advanced soft tissue sarcoma and recurrent ovarian cancer
Quick Facts About Trabectedin Accord
Key Takeaways About Trabectedin Accord
- Hospital-only medication: Trabectedin Accord is administered exclusively in a hospital or clinical setting by oncology specialists experienced in chemotherapy
- Two approved indications: Treats advanced soft tissue sarcoma (as monotherapy) and recurrent ovarian cancer (in combination with PLD)
- Regular monitoring required: Blood tests are essential before and during each cycle to check liver function, blood counts, and muscle enzymes
- Pregnancy contraindicated: Effective contraception is mandatory during treatment and for 3 months (women) or 5 months (men) after the last dose
- Serious side effects possible: Hepatotoxicity, neutropenia, and rhabdomyolysis require immediate medical attention; report fever, muscle pain, or yellowing skin promptly
What Is Trabectedin Accord and What Is It Used For?
Trabectedin Accord 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. This multi-targeted approach makes it effective even in tumors that have developed resistance to other chemotherapy agents.
Approved Indications
Soft Tissue Sarcoma (STS): Trabectedin Accord 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.
Ovarian Cancer: Trabectedin Accord 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 to PLD alone in clinical trials.
The European Medicines Agency (EMA) first authorized trabectedin (as Yondelis) in 2007 for soft tissue sarcoma and in 2009 for ovarian cancer. Trabectedin Accord is a generic version that contains the same active substance and has been shown to be bioequivalent to the reference product.
Trabectedin Accord is typically used as a second-line or later-line treatment. For soft tissue sarcoma, first-line treatment usually involves doxorubicin-based regimens. Trabectedin is particularly effective in certain histological subtypes, including myxoid/round cell liposarcoma and leiomyosarcoma. Your oncologist will determine whether trabectedin is the most appropriate option based on your specific tumor type and treatment history.
What Should You Know Before Taking Trabectedin Accord?
Before starting Trabectedin Accord, 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.
Contraindications
Trabectedin Accord 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 Accord 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
- Fever: May indicate bone marrow suppression or infection – trabectedin can significantly affect blood cell counts and liver function
- Severe nausea, vomiting, or inability to drink fluids with reduced urination despite anti-emetic treatment – risk of dehydration
- Severe muscle pain or weakness: May indicate rhabdomyolysis (muscle breakdown), a potentially life-threatening condition
- Infusion site reactions: Leakage from the vein (extravasation) can cause tissue necrosis requiring surgical intervention
- Allergic reactions: Fever, breathing difficulties, skin redness, rash, nausea, or vomiting
- Unexplained swelling with dizziness or low blood pressure – may indicate capillary leak syndrome requiring urgent assessment
Trabectedin Accord 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.
Pregnancy and Breastfeeding
Trabectedin Accord 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.
- 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 and weakness. 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.
Excipients
Trabectedin Accord 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.
How Does Trabectedin Accord 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.
Major Interactions
The following drugs should be avoided or require close monitoring when used with trabectedin:
| Drug / Class | Effect on Trabectedin | Clinical Recommendation |
|---|---|---|
| Ketoconazole, Fluconazole (antifungals) | Increased trabectedin levels (CYP3A4 inhibition) | Avoid if possible; if necessary, monitor closely for toxicity |
| Ritonavir (HIV protease inhibitor) | Increased trabectedin levels (strong CYP3A4 inhibition) | Avoid concurrent use |
| Clarithromycin (macrolide antibiotic) | Increased trabectedin levels (CYP3A4 inhibition) | Avoid if possible; consider alternative antibiotics |
| Rifampicin (anti-tuberculosis) | Decreased trabectedin levels (CYP3A4 induction) | Avoid concurrent use; may reduce efficacy |
| Phenobarbital (antiepileptic) | Decreased trabectedin levels (CYP3A4 induction) | Avoid if possible; discuss alternatives with neurologist |
| St. John's Wort (herbal supplement) | Decreased trabectedin levels (CYP3A4 induction) | Do not use during treatment |
| Phenytoin (antiepileptic) | Reduced phenytoin efficacy; altered trabectedin metabolism | Concurrent use not recommended |
| Yellow fever vaccine (live vaccine) | Risk of fatal systemic vaccine disease | Contraindicated; other live vaccines also not recommended |
Minor Interactions
The following drugs may alter trabectedin levels or share overlapping toxicity and require monitoring:
| Drug / Class | Concern | Action Required |
|---|---|---|
| Aprepitant (antiemetic) | Moderate CYP3A4 inhibition; may increase trabectedin levels | Monitor for increased toxicity |
| Ciclosporin (immunosuppressant) | CYP3A4 inhibition; may increase trabectedin exposure | Close monitoring required |
| Verapamil (calcium channel blocker) | CYP3A4 inhibition; may increase trabectedin levels | Monitor for toxicity; consider alternative antihypertensive |
| Statins (e.g., atorvastatin, simvastatin) | Additive risk of muscle damage (rhabdomyolysis) | Monitor creatine kinase levels; consider temporary discontinuation |
| Other hepatotoxic drugs | Additive risk of liver damage | Regular liver function monitoring |
Alcohol consumption should be avoided during treatment with Trabectedin Accord, as both trabectedin and alcohol can cause liver damage. The combination may significantly increase the risk of hepatotoxicity.
What Is the Correct Dosage of Trabectedin Accord?
Trabectedin Accord 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 Accord 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.
Adults – Soft Tissue Sarcoma
Standard Dosing Protocol
- Dose: 1.5 mg/m² body surface area
- Infusion duration: Approximately 24 hours via central venous line
- Cycle frequency: Every 3 weeks (21-day cycles)
- Pre-medication: Dexamethasone 20 mg IV 30 minutes before infusion (hepatoprotective and antiemetic)
- Japanese patients: Recommended starting dose is 1.2 mg/m² (lower than other ethnicities)
Adults – Ovarian Cancer (Combination with PLD)
Combination Dosing Protocol
- PLD dose: 30 mg/m² administered first
- Trabectedin dose: 1.1 mg/m² body surface area
- Infusion duration: 3 hours via central venous line
- Cycle frequency: Every 3 weeks (21-day cycles)
- Important: The IV line must be flushed with 5% glucose solution between PLD and trabectedin administration
Children and Adolescents
Trabectedin Accord 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.
Elderly Patients
No specific dose adjustment is required based on age alone. However, elderly patients may be more susceptible to adverse effects, particularly hepatotoxicity and myelosuppression, and may require more frequent monitoring. Dose adjustments are guided by organ function and tolerability rather than chronological age.
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
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.
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
What Are the Side Effects of Trabectedin Accord?
Like all chemotherapy medications, Trabectedin Accord 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. 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.
Serious Side Effects
The following side effects are potentially serious and require prompt medical evaluation:
Very Common (affects more than 1 in 10 patients)
Serious effects occurring frequently
- Elevated bilirubin levels (may cause jaundice – yellowing of skin and eyes)
- Abnormal blood counts (your doctor will order regular blood tests)
- Elevated liver enzymes (hepatotoxicity)
Common (affects 1 to 10 in 100 patients)
Serious effects occurring in some patients
- Blood infections (sepsis) in severely immunocompromised patients – seek immediate care for fever
- Muscle pain (myalgia) and nerve damage causing pain, weakness, or numbness
- Injection site reactions; extravasation can cause tissue necrosis requiring surgery
- Allergic reactions (fever, breathing difficulty, skin rash, nausea, vomiting)
- Syncope (fainting), palpitations, left ventricular dysfunction, pulmonary embolism (with PLD combination)
Uncommon (affects 1 to 10 in 1,000 patients)
Less frequent but potentially serious effects
- Rhabdomyolysis – severe muscle pain, stiffness, weakness, and dark urine; can lead to kidney failure
- Breathing difficulty, irregular heartbeat, decreased urination, mental status changes, low blood pressure with abnormal lab values
- Pulmonary edema (abnormal fluid accumulation in the lungs)
- Capillary leak syndrome – unexplained partial or generalized swelling with dizziness and low blood pressure
- Tissue necrosis at the injection site from extravasation; symptoms may be delayed by hours and include blistering, skin peeling, and darkening
Rare (affects fewer than 1 in 1,000 patients)
Rare but serious effects
- Hepatic failure – jaundice, right upper abdominal pain, nausea, vomiting, general malaise, confusion, drowsiness; seek emergency care immediately
Other Side Effects
Very Common (affects more than 1 in 10 patients)
Non-serious but frequently occurring effects
- Fatigue and weakness
- Shortness of breath and cough
- Back pain
- Edema (fluid retention)
- Increased bruising and nosebleeds
- Increased susceptibility to infections (with possible fever)
- Loss of appetite, nausea, vomiting, abdominal pain, diarrhea, or constipation
- Headache
- Mucositis (inflammation of mucous membranes, mouth sores) – especially with PLD combination
- Hand-foot syndrome (redness, swelling, blistering of palms and soles) – with PLD combination
Common (affects 1 to 10 in 100 patients)
Less frequent non-serious effects
- Dehydration and weight loss
- Digestive discomfort and altered taste
- Hair loss (alopecia)
- Dizziness, low blood pressure, and hot flushes
- Skin rash
- Increased skin pigmentation (with PLD combination)
- Joint pain
- Insomnia
Reporting suspected adverse reactions after authorization of a medicine is important. It allows continued monitoring of the benefit-risk balance. Healthcare professionals and patients are encouraged to report side effects to their national pharmacovigilance authority (e.g., the FDA MedWatch program in the United States, the Yellow Card Scheme in the United Kingdom, or the EMA EudraVigilance system in the European Union).
How Should You Store Trabectedin Accord?
Trabectedin Accord 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 Accord is essential to maintain its stability and efficacy. As a cytotoxic agent, it also requires specific handling and disposal procedures:
- Unopened vials: Store in a refrigerator at 2°C to 8°C. Protect from light and keep in the original carton.
- 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.
- 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.
What Does Trabectedin Accord Contain?
Each vial of Trabectedin Accord contains trabectedin as the active ingredient (0.25 mg or 1 mg per vial) along with sucrose, potassium dihydrogen phosphate, phosphoric acid, and potassium hydroxide as excipients.
Active Ingredient
- Trabectedin Accord 0.25 mg: Each vial contains 0.25 mg of trabectedin
- Trabectedin Accord 1 mg: Each vial contains 1 mg of trabectedin
Inactive Ingredients (Excipients)
- Sucrose (bulking agent and lyoprotectant)
- Potassium dihydrogen phosphate (buffer)
- Phosphoric acid (for pH adjustment)
- Potassium hydroxide (for pH adjustment)
Appearance and Packaging
Trabectedin Accord is supplied as a white to off-white powder for concentrate for solution for infusion. It is provided in type I glass vials. Each outer carton contains one vial with either 0.25 mg or 1 mg of trabectedin. After reconstitution with sterile water for injections (5 mL for the 0.25 mg vial; 20 mL for the 1 mg vial), the solution should be clear, colorless to slightly yellowish, and essentially free from visible particles.
Marketing Authorization
Trabectedin Accord is manufactured by Accord Healthcare and is authorized for sale throughout the European Union and other regulated markets. The marketing authorization holder is Accord Healthcare S.L.U., Barcelona, Spain. Manufacturing sites include Accord Healthcare Polska (Poland), Pharmadox Healthcare Ltd. (Malta), and Accord Healthcare Single Member S.A. (Greece).
Frequently Asked Questions About Trabectedin Accord
Trabectedin Accord is used to treat two types of cancer in adults: advanced soft tissue sarcoma (when previous chemotherapy treatments have failed or are unsuitable) and recurrent ovarian cancer (in combination with pegylated liposomal doxorubicin, for patients whose cancer has responded to prior platinum-based therapy). It works by binding to cancer cell DNA and preventing tumor growth.
Trabectedin Accord is given as an intravenous (IV) infusion in a hospital setting, preferably through a central venous catheter. For soft tissue sarcoma, the infusion takes approximately 24 hours. For ovarian cancer (given after PLD), the infusion takes 3 hours. Treatment cycles are repeated every 3 weeks. Only trained oncology professionals may administer this medication.
The most serious risks include hepatotoxicity (liver damage), myelosuppression (low blood cell counts leading to infections or bleeding), rhabdomyolysis (severe muscle breakdown that can damage kidneys), and capillary leak syndrome. Regular blood tests before each treatment cycle are essential to detect these complications early. Patients should report any fever, muscle pain, dark urine, or yellowing of skin immediately.
No, alcohol consumption should be avoided during treatment with Trabectedin Accord. Both trabectedin and alcohol can cause liver damage, and the combination may significantly increase the risk of hepatotoxicity. Discuss any concerns about alcohol use with your oncologist.
Trabectedin Accord contains the same active ingredient (trabectedin) as Yondelis and is considered bioequivalent. Yondelis was the original brand name when trabectedin was first approved by the EMA in 2007. Trabectedin Accord is a generic version manufactured by Accord Healthcare. Other generic versions include Trabectedin Teva, Trabectedin SUN, and Trabectedin EVER Pharma. All contain the same active substance and are interchangeable as determined by regulatory authorities.
The total duration of treatment depends on how your cancer responds and how well you tolerate the medication. Treatment continues as long as there is clinical benefit and the side effects are manageable. Some patients receive trabectedin for many months. Your oncologist will regularly assess your response through imaging studies and blood tests and will discuss the optimal treatment duration with you.
References
- European Medicines Agency (EMA). Yondelis (trabectedin) – Summary of Product Characteristics. Last updated 2025. Available at: EMA – Yondelis.
- Demetri GD, et al. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma (SAR-3007): a randomised, open-label, phase 3 study. The Lancet Oncology. 2016;17(9):1317–1329. doi:10.1016/S1470-2045(16)30147-8.
- Monk BJ, et al. Trabectedin plus pegylated liposomal doxorubicin in recurrent ovarian cancer. Journal of Clinical Oncology. 2010;28(19):3107–3114. doi:10.1200/JCO.2009.25.4037.
- ESMO/European Sarcoma Network Working Group. Soft tissue and visceral sarcomas: ESMO-EURACAN-GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2021;32(11):1348–1365.
- National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Soft Tissue Sarcoma. Version 2.2025.
- World Health Organization (WHO). WHO Model List of Essential Medicines. 23rd List, 2023.
- D'Incalci M, Galmarini CM. A review of trabectedin (ET-743): a unique mechanism of action. Molecular Cancer Therapeutics. 2010;9(8):2157–2163. doi:10.1158/1535-7163.MCT-10-0263.
- Accord Healthcare S.L.U. Trabectedin Accord – Summary of Product Characteristics. European Medicines Agency. 2025.
About the Medical Editorial Team
This article was written and reviewed by the iMedic Medical Editorial Team, a multidisciplinary group of licensed physicians and pharmacists specializing in oncology, clinical pharmacology, and evidence-based medicine.
Content developed by medical writers with expertise in oncology drug information, based on approved prescribing information, peer-reviewed clinical studies, and international treatment guidelines (EMA, FDA, ESMO, NCCN, WHO).
Independently reviewed by board-certified oncology specialists and clinical pharmacologists. All medical claims verified against primary sources with evidence level 1A where available.
Last medical review: | Evidence framework: GRADE | Conflict of interest: None declared | Funding: Independent, no commercial sponsorship