Topotecan for brain mets of solid tumors – pro

Despite advances in the treatment of systemic malignancies, the prognosis for patients with brain metastases continues to be poor. Radiation and steroetactic radiation approaches palliate selected metstases and temsazolomide is often used becasue it crosses the blood-brain barrier. Topotecan, a topoisomerase I inhibitor, also freely crosses the blood-brain barrier and may be effective in both the therapeutic and prophylactic settings in patients with brain metastases. Over the last two decades studies demonstrated the antitumor activity of topotecan against brain metastases, with objective response rates ranging from 33%-63% in patients with various solid tumors. For example, Oberhoff et al. reported a 37% objective response rate (one CR, five PRs) in 24 women treated with topotecan (1.5 mg/m2 daily for 5 days every 3 weeks) for new brain metastases, with hematologic toxicity being the major side effect.

The antitumor response in the central nervous system was often greater and occurred more quickly than the systemic antitumor response to topotecan treatment. Early studies have also suggested that topotecan, an apparent radiosensitizer.

At this time, 2012 NCCN only lists topotecan for small cell lung cancer brain mets.

Eric T. Wong and Anna Berkenblit The Role of Topotecan in the Treatment of Brain Metastases
The Oncologist February 2004 vol. 9 no. 1 68-79

Dose-dense temozolomide regimen for the treatment of brain metastases from melanoma, breast cancer, or lung cancer not amenable to surgery or radiosurgery: a multicenter phase II study
Ann Oncol March 1, 2010 21 (3) 655-661

A. F. Eichler et al, Multidisciplinary Management of Brain Metastases
The Oncologist July 1, 2007 12 (7) 884-898

Oberhoff C, Kieback DG, Wurstlein R, et al. Topotecan chemotherapy in patients with breast cancer and brain metastases: Results of a pilot study. Onkologie 2001;24:256-260.

nccn, CNS Cancer, Brain- D, 3

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