Treatment of astrocytes-tumor cells inhibitors of endothelin receptors

Abstract

The disclosure relates to an endothelin receptor antagonist for use in the prevention or treatment of brain metastases in combination with a cytotoxic chemotherapy agent, radiotherapy or both. The endothelin receptor antagonist may for example be bosentan, macitentan or a mixture of bosentan and macitentan.

Description

BACKGROUND[0001]Brain metastasis is one of the most difficult challenges facing oncology. Metastatic tumors are resistant to most chemotherapy agents. The treatments for brain metastasis are primarily whole brain and focused radiotherapy, with surgical resection of tumors in a minority of cases. Most chemotherapy regimens involve 2-3 agents such as cisplatin, cyclophosphamide, etoposide, teniposide, mitomycin, irinotecan, vinorelbine, etoposide, ifosfamide, temozolomide and fluorouracil (5-FU). These are administered in combination with radiotherapy. The effect of these chemotherapies on prolonging survival is generally less than a year. A fairly new chemotherapy for brain tumors is temozolomide used with whole-brain irradiation. Results are preliminary but temozolomide appears to have some limited effect on the response rate compared to radiation alone and appears to have some clinical activity in combination with radiation in phase II trials.[0002]Despite intense efforts, the limi...

AI Technical Summary

Benefits of technology

The patent text describes a combination of an endothelin receptor antagonist and a cytotoxic chemotherapy agent for the prevention or treatment of brain metastases. The endothelin receptor antagonist can be used with various chemotherapy agents such as alkylating agents, platinum drugs, antimetabolite drugs, anti-tumor antibiotics, and mitotic inhibitors. The combination can help protect neurons from damage and reduce the risk of brain metastasis.

Problems solved by technology

Brain metastasis is one of the most difficult challenges facing oncology.

Results are preliminary but temozolomide appears to have some limited effect on the response rate compared to radiation alone and appears to have some clinical activity in combination with radiation in phase II trials.

Despite intense efforts, the limited medical options available for brain metastasis have remained poor and too often more palliative than therapeutically effective.

This state of affairs has been long recognized but, to date, significant advances have not materialized.

Thus, one of skill in the art realizes that a treatment may improve the patient's condition but may not be a complete cure of the disease.

(2000), Expression of vascular endothelial growth factor is necessary but not sufficient for production and growth of brain metastasis.

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