Yondelis - trabectedin

What is Yondelis?

Yondelis is a powder that is made up into a solution for infusion (drip into a vein). Contains the active ingredient trabectedin.

What is Yondelis used for?

Yondelis is indicated in the treatment of adults with advanced soft tissue sarcoma, a type of cancer that develops from the soft supporting tissues of the body. It is used when therapy with anthracycline and ifosfamide (other anticancer medicines) is no longer effective or when these medicines cannot be given to patients.

Because the number of patients with soft tissue sarcoma is low, the disease is considered "rare" and Yondelis was designated an "orphan medicine" (a medicine used in rare diseases) on 30 May 2001.

The medicine can only be obtained with a prescription.

How is Yondelis used?

Yondelis should be given under the supervision of a doctor experienced in the use of chemotherapy (medicines used to treat cancer). Its use should be limited to qualified oncologists (doctors specialized in treating cancer) or to other health professionals specialized in the administration of cytotoxic drugs (ie able to destroy cells).

The recommended dose of Yondelis is 1.5 mg per square meter of body surface area (calculated based on the patient's height and weight), administered as a single infusion over 24 hours every three weeks. Treatment can be continued until the patient benefits. Administration of Yondelis by central venous line is recommended (via a thin tube leading from the skin to the main veins, just above the heart). To prevent vomiting and protect the liver, dexamethasone (a corticosteroid) should be given by infusion before each dose of Yondelis. In the presence of abnormalities in blood counts (eg low white blood cell or platelet counts) the Yondelis injection should be delayed or the dose should be reduced. For more information, see the summary of product characteristics (also included with the EPAR).

How does Yondelis work?

The active substance in Yondelis, trabectedin, is an anticancer medicine. This is the synthetic version of a chemical originally extracted from a species of tunicate or "ascidian" (a marine invertebrate). Cancer is a disease in which cells divide too quickly, usually due to the malfunctioning of their genes. Trabectedin works by binding to DNA, the chemical molecule that genes are made of, and by preventing some genes in human cells from increasing their activity. In this way the cells are no longer able to divide rapidly and the growth of various types of tumors, including sarcoma, is slowed.

What studies have been carried out on Yondelis?

The effects of Yondelis were first tested in experimental models before being studied in humans.

Yondelis was also analyzed in a main study involving 266 patients with liposarcoma (a sarcoma originating in fat cells) or leiomyosarcoma (a sarcoma originating in "smooth" or involuntary muscle cells) at an advanced or metastatic stage (which has spread to other parts of the body). All patients had previously been treated with anthracycline and ifosfamide, but the therapy had ceased to be effective. The study compared two different dosage regimes of Yondelis: three times a month or once every three weeks. The main measure of effectiveness was the patients' life time without worsening the disease. At the time of the assessment the study was still ongoing.

What benefit has Yondelis shown during the studies?

Yondelis was more effective when administered once every three weeks than the other dosing regimen. Patients who received it once every three weeks lived on average 3.8 months without their disease getting worse, compared with 2.1 months for patients treated with Yondelis three times a month.

What is the risk associated with Yondelis?

The most common side effects of Yondelis (seen in more than 1 patient in 10) are increased blood creatine phosphokinase (an indicator of catabolism, ie disintegration, muscle) and creatinine (an enzyme marker of kidney disease), decreased levels of albumin in the blood (a marker of liver problems), neutropenia (decrease in the number of neutrophils, a type of white blood cell), thrombocytopenia (low blood platelet count), anemia (low red blood cell count), leukopenia (reduction of leukocyte level, a type of white blood cell), headache, vomiting, nausea, constipation, loss of appetite, fatigue, asthenia (weakness), hyperbilirubinemia (increased bilirubin levels in the blood) and increased levels of liver enzymes in blood (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma-glutamyltransferase). For the full list of all side effects reported with Yondelis, see the Package Leaflet.

Yondelis should not be used in people who may be hypersensitive (allergic) to trabectedin or any of the other ingredients. It must not be used in patients with severe or uncontrolled infections of any kind or in combination with the yellow fever vaccine or during breast-feeding.

Why has Yondelis been approved?

The Committee for Medicinal Products for Human Use (CHMP) concluded that the benefits of Yondelis outweigh its risks in the treatment of patients with advanced soft tissue sarcoma after failure of anthracycline and ifosfamide therapy or who are not eligible for receive such agents. The committee noted that evidence of the effects of Yondelis is mainly based on the treatment of liposarcoma and leiomyosarcoma. The committee recommended the granting of the marketing authorization for Yondelis.

Yondelis was authorized in "exceptional circumstances". This means that, being the disease rare, it was not possible to obtain complete information on Yondelis. The European Medicines Agency will review the new information available each year and, if necessary, this summary will be updated.

What information is still awaited for Yondelis?

The company that produces Yondelis will continue to evaluate which patients are more likely to respond to the drug.

More information on Yondelis

On 17 September 2007, the European Commission granted a marketing authorization for Yondelis, valid throughout the European Union, to Pharma Mar, SA.

For a summary of the opinion of the Committee for Orphan Medicinal Products click here.

The full EPAR for Yondelis can be found here.

Last update of this summary: 05-2009.