A pilot study of amiodarone with infusional doxorubicin or vinblastine in refractory breast cancer.

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  • Additional Information
    • Source:
      Publisher: Springer Verlag Country of Publication: Germany NLM ID: 7806519 Publication Model: Print Cited Medium: Print ISSN: 0344-5704 (Print) Linking ISSN: 03445704 NLM ISO Abbreviation: Cancer Chemother Pharmacol Subsets: MEDLINE
    • Publication Information:
      Publication: Berlin : Springer Verlag
      Original Publication: Berlin, New York, Springer International.
    • Subject Terms:
      Amiodarone/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy ; Doxorubicin/*therapeutic use ; Vinblastine/*therapeutic use; ATP Binding Cassette Transporter, Subfamily B, Member 1/biosynthesis ; Administration, Oral ; Adult ; Aged ; Amiodarone/administration & dosage ; Amiodarone/adverse effects ; Amiodarone/blood ; Biopsy ; Breast Neoplasms/ultrastructure ; Doxorubicin/administration & dosage ; Doxorubicin/adverse effects ; Doxorubicin/blood ; Drug Resistance ; Female ; Humans ; Immunohistochemistry ; Infusions, Intravenous ; Middle Aged ; Pilot Projects ; Vinblastine/administration & dosage ; Vinblastine/adverse effects ; Vinblastine/blood
    • Abstract:
      Increasing evidence suggests that P-glycoprotein (Pgp) expression can mediate drug resistance in refractory breast cancer. We studied 33 patients with refractory breast cancer enrolled in a pilot study of oral amiodarone as a Pgp antagonist given in combination with infusional doxorubicin or vinblastine. Whenever possible, tumors were biopsied and Pgp expression was assayed. Patients received either 60 mg/m2 doxorubicin over 96 h or 8.5 mg/m2 vinblastine over 120 h by continuous intravenous infusion. Beginning with the second cycle of chemotherapy, 600-800 mg amiodarone was given orally each day. Patients who experienced toxicity due to amiodarone but were responding to chemotherapy were placed on quinidine. Partial responses were observed in 9 of 33 patients on study and were sometimes observed after the first cycle of chemotherapy, before amiodarone was given, suggesting that some patients may have responded to treatment because of the infusional schedule. Toxicities were primarily the known side effects of the antineoplastic agents and of amiodarone. The major amiodarone toxicity was gastrointestinal, with nausea, vomiting, anorexia, or diarrhea being noted in 21 patients. Biopsy samples were obtained from 29 patients and in 21 cases, viable tumor tissue was present and the results were interpretable. Of the 21 samples, 9 had Pgp expression as determined by immunohistochemical staining; 12 were considered negative. The presence of Pgp expression was associated with an acceleration of the time to treatment failure. Whereas normal-tissue toxicities related to the combination of a Pgp antagonist with chemotherapy were not observed, amiodarone was associated with too many untoward effects to be utilized as a drug resistance-reversing agent.
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    • Accession Number:
      0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
      5V9KLZ54CY (Vinblastine)
      80168379AG (Doxorubicin)
      N3RQ532IUT (Amiodarone)
    • Publication Date:
      Date Created: 19950101 Date Completed: 19950413 Latest Revision: 20181130
    • Publication Date:
      20240829
    • Accession Number:
      10.1007/BF00686829
    • Accession Number:
      7882454