The role of chemotherapy in the treatment of patients with brain metastases from solid tumors

Abstract

Brain metastases are the most frequent cancer in the central nervous system, being ten times more common than primary brain tumors. Patients generally have a poor outcome with a median survival of 4 months after diagnosis of the metastases. Therapeutic options include surgery, stereotactic, radiosurgery, whole-brain radiotherapy (WBRT), and chemotherapy. Patients with a limited number of brain metastases and well-controlled systemic cancer benefit from brain metastases-specific therapies, including surgery, radiosurgery, and conventional radiation. The role of chemotherapy for brain metastases remains limited. There is concern about drug delivery because of the blood-brain barrier. However, higher response rates are noted with initial therapies, suggesting that part of the poor response rate may be related to the late onset of brain metastases and the use of second- and third-line regimens. Recent studies have demonstrated objective responses with systemic therapy in a variety of cancer types, especially when combined with WBRT. Individual therapeutic strategies for central nervous system metastases must be chosen based on performance status, the extent of intracranial disease, and the chemosensitivity of the underlying tumor, as well as the control of the systemic cancer. In this article we review important prognostic factors and challenges in using chemotherapy. We specifically review recent advances in the treatment of brain metastases from breast and lung cancer as well as melanoma. Future treatment advances will require a multidisciplinary approach integrating surgical, radiation, and chemotherapeutic options to improve neurological function and quality of life, rather than just focusing on survival endpoints.

Effect of chemotherapy on survival after whole brain radiation therapy for brain metastases: a single-center retrospective analysis

“…Recently, the activity of chemotherapy in brain metastasis is highlighted (Robinet et al 2001;Walbert and Gilbert 2009;Mehta et al 2010). Concurrent chemoradiation therapies with BBB permeable agents, such as Temozolamide or topotecan are currently under investigation in prospective clinical trials.…”

Radiation-Refractory Brain Metastases in Patients with Non-Small Cell Lung Cancer

“…Previous studies have questioned the importance of the blood-brain barrier in shielding brain metastases from chemotherapy; these studies have reported intracranial tumor response rates of 30% to 50% in solid tumor cancer patients, although overall survival in these trials remained modest. 8 Furthermore, small prospective studies have reported intracranial tumor response rates of 50% to 80% with the use of erlotinib with the more favorable rates derived from lung cancer patients with tumors with epidermal growth factor receptor mutations. 9 However, to our knowledge, none of these studies focused on highly symptomatic patients with radiation-refractory brain metastases.…”

State of the art of chemotherapy for the treatment of central nervous system metastases from non-small cell lung cancer

“…Free diffusion of molecules across the BBB requires both lipophilicity and a molecular mass smaller than 0.5 kDa. Chemotherapy drugs are generally more than 150 kDa large, hydrophilic, and often protein-bound molecules, therefore unable to penetrate an intact BBB (21). Furthermore, chemotherapy drugs are often substrate of active efflux transport proteins, such as P-glycoprotein, which can be highly expressed by the BBB and it is responsible for the transport of compounds from the brain into the circulation (22).…”