What is the role of chemotherapy in the treatment of brain metastasis?

Updated: Aug 01, 2018
  • Author: Victor Tse, MD, PhD; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
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Medical treatment directed at cancer cells that have seeded into the brain is ineffective. The failure of chemical therapy has always been attributed to an intact BBB and the acquisition of drug resistance by the cancer cells. Most tumors that metastasize to the brain are not chemosensitive, though small-cell lung cancer, breast cancer, and lymphoma respond to chemotherapy. Hence, management and treatment depend on the systemic disease, the tumor type, and the stage of the disease.

A variety of chemotherapeutic agents have been used to treat brain metastasis from lung, breast, and melanoma, including cisplatin, cyclophosphamide, etoposide, teniposide, mitomycin, irinotecan, vinorelbine, etoposide, ifosfamide, temozolomide, fluorouracil (5FU), and prednisone.

In most cases, 2-3 of these agents are used in combination and in conjunction with whole-brain radiation therapy (WBRT). The outcome with this approach is not promising. The mean survival for chemotherapy alone for small-cell lung and breast cancer and melanoma is about 3.2-8 months. Survival with the combination of chemotherapy and WBRT is about 3.5-13 months.

Chemotherapy can have a remission rate of above 10%, a partial-response rate of about 40%, and a local-control rate of about 9%.

Temozolomide has recently been used as a single agent to treat brain metastasis from breast cancer. The result is encouraging. Complete remission was achieved in 36% of patients, and an additional 58% had a partial response.

The advent in small-molecule tyrosine kinase inhibitors (tyrKi) and monoclonal antibodies has helped transform the management of brain metastasis. Gefitinib and erlotinib, epidermal growth factor receptor (EGFR) tryKis, have shown promising results in treating nonsmall cell lung cancers that metastasize to the brain, especially if they have the EGFR mutation. [13] The use of lapatinib in combination with capecitabine is effective in treating HER2 -ositive brain metastasis; similarly, the use of vemurafenib in treating BRAF V600E–positive melanoma that has brain metastasis is also found to be effective. [14] It is noteworthy that a recent study at Memorial Sloan-Kettering has shown that the use of sorafenib or sunitinib can lower the incidence of metastasis of renal cell carcinoma to the brain. [15]

Monoclonal antibodies such as trastuzumab have been used in treating metastatic breast cancer. The latter, however, is not that effective in crossing the blood-brain barrier and results in relapse within the central nervous system. Ipilimumab, on the other hand, has been found to be effective in treating metastatic melanoma to the brain. [16]

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