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Preclinical evaluation of aclacinomycin A for the intraperitoneal treatment of human ovarian carcinoma

  • Original Articles
  • Pharmacokinetics, Aclacinomycin A
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Summary

Combination chemotherapy regimens have produced a pathological complete response rate of only 1%–25% in patients with advanced ovarian cancer. Patients with small-volume residual disease after treatment are refractory to further systemic therapy, and most eventually die of their disease. Intraperitoneal (i.p.) chemotherapy, particularly with adriamycin or cisplatin has shown promise in these patients. However, the dose-limiting painful peritonitis associated with i.p. adriamycin makes this regimen potentially too toxic for many patients. Aclacinomycin A, another anthracycline antibiotic, has been found to have activity against a wide variety of murine tumors and human xenografts. It has also demonstrated clinical efficacy in phase I and II trials against refractory ovarian cancer and has less pronounced vesicant properties than adriamycin, making it an ideal candidate for i.p. use in ovarian cancer patients. In vitro clonogenic assays utilizing a battery of adriamycin-sensitive and-resistant human ovarian carcinoma cell lines have shown that aclacinomycin a is more cytotoxic than adriamycin in all cell lines tested. In addition, aclacinomycin A was found to prolong survival in a nude mouse xenograft of i.p. human ovarian cancer. These results have provided the experimental rationale for an ongoing clinical trial of i.p. aclacinomycin in refractory ovarian cancer patients at the Medicine Branch, NCI.

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Authors and Affiliations

  1. Clinical Pharmacology Branch, Division of Cancer Treatment, National Cancer Institute, 20892, Bethesda, MD, USA

    Charles E. Myers

  2. Medicine Branch, National Cancer Institute, Building 10, Room 12N226 9000 Rockville Pike, 20892, Bethesda, MD, USA

    Karen G. Louie, Thomas C. Hamilton, Brent C. Behrens, Karen R. Grotzinger, Wilma M. McKoy, Robert C. Young & Robert F. Ozols

Authors
  1. Karen G. Louie
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  2. Thomas C. Hamilton
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  3. Brent C. Behrens
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  4. Karen R. Grotzinger
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  5. Wilma M. McKoy
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  6. Charles E. Myers
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  7. Robert C. Young
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  8. Robert F. Ozols
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Louie, K.G., Hamilton, T.C., Behrens, B.C. et al. Preclinical evaluation of aclacinomycin A for the intraperitoneal treatment of human ovarian carcinoma. Cancer Chemother. Pharmacol. 18, 153–156 (1986). https://doi.org/10.1007/BF00262286

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  • DOI: https://doi.org/10.1007/BF00262286

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