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5,6-Dimethylxanthenone-4-Acetic Acid (DMXAA)

Clinical Potential in Combination with Taxane-Based Chemotherapy

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American Journal of Cancer

Abstract

Currently, there is a great deal of interest in drugs that target tumor vasculature and their therapeutic potential in combination regimens for the treatment of cancer. This review focuses on one of the vascular disrupting agents, 5-6-dimethylxanthenone 4-acetic acid (DMXAA), and the rationale for its combination with standard taxane-based chemotherapy. DMXAA and taxanes have different mechanisms of action and, in combination, demonstrate at least additive activity against preclinical solid tumors. Their clinical adverse-effect and pharmacologic profiles as single agents appear to render these agents suitable for use in combination. Phase I studies of DMXAA have identified a range of doses for combination clinical trials. In addition, the clinical indications and chemotherapy doses for combination clinical studies have been selected from positive randomized controlled trials of taxanes in advanced cancers. A phase II clinical trials program of combination studies with DMXAA is now underway; paclitaxel and carboplatin in patients with NSCLC and ovarian cancer and docetaxel in patients with hormone-refractory prostate cancer are being evaluated.

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Acknowledgments

LR Kelland is an employee of Antisoma. Antisoma have provided support for some of the work described in this review.

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Authors and Affiliations

  1. Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand

    Mark J. McKeage

  2. Antisoma Research Laboratories, St Georges Hospital Medical School, London, UK

    Lloyd R. Kelland

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  1. Mark J. McKeage
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  2. Lloyd R. Kelland
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Correspondence to Mark J. McKeage.

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McKeage, M.J., Kelland, L.R. 5,6-Dimethylxanthenone-4-Acetic Acid (DMXAA). Am J Cancer 5, 155–162 (2006). https://doi.org/10.2165/00024669-200605030-00002

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  • DOI: https://doi.org/10.2165/00024669-200605030-00002

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