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Tazemetostat

Tazemetostat is an EZH2 methyltransferase blocker, for the treatment of patients aged ≥16 years with metastatic or locally advanced epithelioid sarcoma.

EZH2 is a histone methyltransferase and a component of the Polycomb repressive complex 2 (PRC2).

This complex deposits epigenetics methylation markers which suppressed genes that control cell differentiation and halt transition of B cells from terminal differentiation.

Epithelioid sarcoma is a subtype of soft-tissue sarcoma.

The disease must not be able to be completely respected.

Tradename Tazverik

Epithelioid sarcoma accounts for less than one percent of all soft-tissue sarcomas.

Epithelioid sarcoma usually begins in the soft-tissue area under the skin of an extremity.

With localized disease, surgery is the standard treatment.

Chemotherapy or radiation may also be used, but the likelihood of progression to metastatic disease is high with these treatments; approximately 50% of people have metastatic disease at the time of diagnosis.

In a clinical trial of 62 patients with metastatic or locally advanced epithelioid sarcoma receiving 800 mg of tazemetostat twice daily until disease progression or unacceptable toxicity.

The overall response rate was 15%, consisting of 1.6% complete responses and 13% partial responses.

67% of patients had a response lasting >6 months.

The most common adverse events were pain, fatigue, nausea, decreased appetite, vomiting, constipation, thrombocytopenia, dry skin, neutropenia, and diarrhea.

It is approved for the treatment of patients with relapse/refractory follicular lymphoma with an EZH2 mutation who have received at least two prior systemic therapies.

The drug is approved with the diagnostic test for the EZH2 mutation.

It is associated with an increased risk for secondary malignancies, including T-cell lymphoblastic lymphoma, myelodysplastic syndrome, and acute myeloid leukemia, and the drug can also cause harm to a fetus.

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