This Article Full Text Full Text (PDF) eLetters: Submit a response to this article Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article link to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wong, E. T. Articles by Berkenblit, A. Search for Related Content PubMed PubMed Citation Articles by Wong, E. T. Articles by Berkenblit, A.

The Role of Topotecan in the Treatment of Brain Metastases

Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

Correspondence: Eric T. Wong, M.D., Brain Tumor Center & Neuro-Oncology Unit, Department of Neurology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, Massachusetts 02215, USA. Telephone: 617-667-1665; Fax: 617-667-1664; e-mail: ewong{at}bidmc.harvard.edu

Despite advances in the treatment of systemic malignancies, the prognosis for patients with brain metastases continues to be dismal. Because the majority of cytotoxic agents seem to be unable to penetrate the blood-brain barrier, the role of chemotherapy in the treatment of brain metastases remains controversial. However, growing amounts of both laboratory and clinical data suggest that a few of the newly developed cytotoxic agents can cross the blood-brain barrier and may have a role in the treatment of patients with brain metastases. Topotecan, a novel topoisomerase I inhibitor, freely crosses the blood-brain barrier and may be clinically effective in both the therapeutic and prophylactic settings in patients with brain metastases. Recent studies have demonstrated the antitumor activity of topotecan against brain metastases, with objective response rates ranging from 33%-63% in patients with various solid tumors. The antitumor response in the central nervous system was often greater and occurred more quickly than the systemic antitumor response to topotecan treatment. This result may be explained by the lack of exposure of brain metastases to previous cytotoxic agents, suggesting a role for topotecan in patients with brain metastases. Early studies have also suggested that topotecan, an apparent radiosensitizer, may be particularly effective in combination with radiotherapy, the current standard of care for patients with brain metastases. In addition, preliminary data suggest that topotecan in combination with temozolomide (another cytotoxic agent that can cross the blood-brain barrier) may have synergistic antitumor activity against brain metastases. This review summarizes the available preclinical and clinical evidence for the role of topotecan in the treatment of brain metastases and concludes with three case studies.

Key Words. Brain metastases • Neoplasms • Drug therapy • Temozolomide • Topoisomerase I inhibitor • Topotecan

This article has been cited by other articles:

				S. Siena, L. Crino, M. Danova, S. Del Prete, S. Cascinu, S. Salvagni, I. Schiavetto, M. Vitali, and E. Bajetta 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. Onc., September 18, 2009; (2009) mdp343v1. [Abstract] [Full Text] [PDF]

				N. A. de Vries, J. Zhao, E. Kroon, T. Buckle, J. H. Beijnen, and O. van Tellingen P-Glycoprotein and Breast Cancer Resistance Protein: Two Dominant Transporters Working Together in Limiting the Brain Penetration of Topotecan Clin. Cancer Res., November 1, 2007; 13(21): 6440 - 6449. [Abstract] [Full Text] [PDF]

				D. C. Gammon, M. S. Bhatt, L. Tran, A. Van Horn, M. Benvenuti, and M. J. Glantz Intrathecal topotecan in adult patients with neoplastic meningitis. Am. J. Health Syst. Pharm., November 1, 2006; 63(21): 2083 - 2086. [Abstract] [Full Text] [PDF]

				D. J. Stewart Topotecan in the First-Line Treatment of Small Cell Lung Cancer Oncologist, December 1, 2004; 9(suppl_6): 33 - 42. [Abstract] [Full Text] [PDF]