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Phase I/II study of IV topotecan in combination with whole brain radiation for the treatment of brain metastases

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Abstract

A phase I/II trial was conducted to determine the toxicities and efficacy (overall response, overall survival, and progression-free survival) of the combination of topotecan and whole brain radiation therapy (XRT) in patients with brain metastases. Patients received 30 Gy XRT given in 10 fractions to the whole brain. In phase I, patients were treated in groups of three at each topotecan dose level; dose escalation proceeded until the maximum tolerated dose (MTD) was identified. The dose-limiting toxicity proved to be grade IV neutropenia at 0.6 mg/m2/d, resulting in an MTD of 0.5 mg/m2/d. One of nine patients showed a response to treatment, and that was partial (OR 11%). Three had stable disease (33%), and four experienced progressive disease (44%). Median progression-free survival was 60 d; median overall survival was 102 d. Intravenous topotecan at 0.5 mg/m2/d concomitant to XRT with 30 Gy in 3-Gy fractions is tolerable in patients with brain metastases. This regimen has the additional advantage of providing systemic treatment to patients with metastases in other locations while whole brain radiation is in progress. Although response and survival outcomes in this small study do not appear higher than expected from historical controls, these were not primary end points, and larger studies on this topic would be useful to elucidate the efficacy of this combination treatment regimen.

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Authors and Affiliations

  1. Radiation Oncology, UCSD Cancer Center, UCSD Medical Center, 200 W Arbor Dr, 92103, San Diego, CA

    Alireza Mirmiran & Matthew A. Spear M.D.

  2. Medical Oncology, San Diego Cancer Research Institute, San Diego, CA

    Edward McClay

Authors
  1. Alireza Mirmiran
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  2. Edward McClay
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  3. Matthew A. Spear M.D.
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Correspondence to Matthew A. Spear M.D..

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Mirmiran, A., McClay, E. & Spear, M.A. Phase I/II study of IV topotecan in combination with whole brain radiation for the treatment of brain metastases. Med Oncol 24, 147–153 (2007). https://doi.org/10.1007/BF02698033

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  • DOI: https://doi.org/10.1007/BF02698033

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