Trabectedin, known commercially as Yondelis, is a chemotherapy medication for certain cancers. It originated from the Caribbean tunicate Ecteinascidia turbinata but is now produced synthetically. It is used when other treatment options may not be suitable or have been exhausted.
How Trabectidin Targets Cancer
Trabectedin interferes with processes within cancer cells. It binds to the minor groove of DNA, causing the DNA helix to bend towards the major groove. This interaction disrupts the normal function of DNA, which is crucial for cell survival and division.
The drug’s activity extends to interfering with DNA-binding proteins and transcription factors. It inhibits transcription, the process of creating RNA from DNA. This interference can lead to the ubiquitination and degradation of RNA polymerase II, an enzyme involved in transcription.
Trabectedin also impacts DNA repair systems, including transcription-coupled nucleotide excision repair and homologous recombination. By disrupting these repair mechanisms, the drug can induce lethal DNA double-strand breaks, ultimately leading to cell cycle arrest and programmed cell death in cancer cells.
Cancers Treated by Trabectidin
Trabectedin is approved for advanced soft tissue sarcoma (STS) and ovarian cancer. For STS, it is used in patients who have previously received other chemotherapy agents like doxorubicin or ifosfamide, or for whom these agents are not suitable. It has demonstrated particular activity in certain STS subtypes, including leiomyosarcomas and liposarcomas, especially myxoid liposarcomas.
For ovarian cancer, trabectedin is indicated for patients with relapsed, platinum-sensitive disease. It is often administered in combination with pegylated liposomal doxorubicin for this indication. The drug offers an alternative treatment strategy when the cancer has returned after initial platinum-based chemotherapy. Its distinct mechanism of action and limited cross-resistance with other agents make it a valuable option in these challenging clinical situations.
Receiving Trabectidin and Managing Side Effects
Trabectedin is administered intravenously. The typical treatment schedule involves administering 1.5 mg/m² of the drug as a 24-hour infusion, usually every three weeks. This cyclical approach allows for periods of recovery between doses.
Patients receiving trabectedin may experience various side effects, which are carefully monitored by healthcare providers. Common side effects include nausea, fatigue, and elevation of liver enzymes, such as transaminase levels. These liver enzyme elevations are frequently observed and are usually transient.
Changes in blood counts are also potential side effects, including neutropenia (low white blood cell count) and thrombocytopenia (low platelet count). These hematological effects are considered dose-limiting toxicities and require close monitoring. Patients are advised to report any symptoms they experience to their medical team promptly, as managing these side effects is an important part of the treatment process.
Key Considerations for Patients
Before initiating trabectedin treatment, patients undergo various assessments to determine their suitability and to establish baseline health parameters. This includes evaluating liver function through blood tests, as liver toxicity, characterized by elevated transaminase levels, is a frequently observed side effect. Cardiac function may also be assessed to ensure the patient’s heart can tolerate the treatment.
Throughout the course of treatment, continuous monitoring is conducted to track the patient’s response and to manage any emerging side effects. Regular blood tests are performed to check liver enzyme levels and blood cell counts, helping to detect and address potential issues like neutropenia or thrombocytopenia early. Adjustments to the treatment schedule or dosage may be considered based on these monitoring results.
Patients should also discuss all other medications they are taking with their oncology team to identify any potential drug interactions with trabectedin. Specific warnings apply to patients with pre-existing liver conditions, as they may be at a higher risk for liver-related side effects. Treatment decisions are individualized, with the oncology team considering the patient’s overall health, cancer type, and previous treatments to determine the most appropriate course of action.