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Phase I trial of combined therapy with bleomycin and the calmodulin antagonist, trifluoperazine

  • Original Articles
  • Bleomycin, Calmodulin Antagonist, Trifluoperazine, Phase I Trial
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Summary

Calmodulin antagonists, such as trifluoperazine, can enhance the cytotoxic effects of bleomycin both in tissue culture and in vivo. Therefore, we evaluated the effects of combination treatment with these drugs in a phase I clinical trial. Patients with objectively measurable or evaluable cancer refractory to conventional treatment who had an acceptable performance status (ECOG 0-2) and acceptable laboratory studies were eligible. All patients gave written informed consent. A cycle of therapy consisted of three weekly treatments with trifluoperazine (days 1–4) and 30 IU bleomycin (day 3). After three patients completed a cycle of therapy without experiencing dose-limiting toxicity, new patients were entered in the study and received a higher dose of trifluoperazine. The dose of bleomycin remained constant. Evaluable patients received at least 2 weeks of treatment and survived for 6 weeks; of 19 patients, 2 were unevaluable. The major toxicities were neurological and pulmonary and included one case of fatal pneumonia with interstitial pulmonary fibrosis. There was no hematologic toxicity. Two patients underwent partial responses (PRs) and two had complete responses (CRs). We conclude that trifluoperazine can safely by given with bleomycin and that further study of the potential efficacy of this treatment is indicated.

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Author information

Authors and Affiliations

  1. Department of Internal Medicine, Yale University School of Medicine, Comprehensive Cancer Center, 06510, New Haven, CT, USA

    William N. Hait, Henry J. Durivage & Kathleen White

  2. Department of Pharmacology, Yale University School of Medicine, Comprehensive Cancer Center, 06510, New Haven, CT, USA

    William N. Hait, Steve Morris & John S. Lazo

  3. Department of Obstetrics and Gynecology, Yale University School of Medicine, Comprehensive Cancer Center, 06510, New Haven, CT, USA

    Steve Morris & Peter E. Schwartz

  4. Department of Internal Medicine, University of California at Los Angeles, 50024, Los Angeles, CA, USA

    Robert J. Figlin

Authors
  1. William N. Hait
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  2. Steve Morris
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  3. John S. Lazo
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  4. Robert J. Figlin
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  5. Henry J. Durivage
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  6. Kathleen White
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  7. Peter E. Schwartz
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Additional information

This work was supported by grants from Bristol-Meyers, the National Cancer Institute (CAO8341, CA-4388), and the American Cancer Society (CH302A)

Dr. Hait is a Burroughs Wellcome Scholar in Clinical Pharmacology

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Hait, W.N., Morris, S., Lazo, J.S. et al. Phase I trial of combined therapy with bleomycin and the calmodulin antagonist, trifluoperazine. Cancer Chemother. Pharmacol. 23, 358–362 (1989). https://doi.org/10.1007/BF00435836

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  • DOI: https://doi.org/10.1007/BF00435836

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