Abstract
Thirty-one patients were entered into a pilot study combining oral quinidine with epirubicin 100 mg m-2 as first line chemotherapy in advanced breast cancer. Three patients were treated with quinidine 1 g b.d., and developed symptoms of toxicity. Of eight subsequent patients treated with quinidine 500 mg b.d., two experienced tiredness and nausea and one severe oral toxicity with epirubicin. The remaining 20 patients received quinidine 250 mg b.d.; one developed cinchonism and one malaise, the remainder showing no excess toxicity compared with epirubicin alone. The median nadir WBC was similar with or without quinidine (2.3 vs 1.6 x 10(9) l-1) as was median nadir platelet count (175 vs 157 x 10(9) l-1). There was no evidence of significant cardiac toxicity. The median plasma quinidine level achieved was 5.6 mumol l-1 (range 2.1-22.1), which is within the range of concentrations which is effective in vitro at reversing experimental anthracycline resistance. A randomised controlled study is proposed to assess the impact of this potential modulation on the efficacy of epirubicin in advanced breast cancer.
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- Carter S. K. Adriamycin-a review. J Natl Cancer Inst. 1975 Dec;55(6):1265–1274. doi: 10.1093/jnci/55.6.1265. [DOI] [PubMed] [Google Scholar]
- Kaye S. B. The multidrug resistance phenotype. Br J Cancer. 1988 Dec;58(6):691–694. doi: 10.1038/bjc.1988.291. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsuruo T., Iida H., Kitatani Y., Yokota K., Tsukagoshi S., Sakurai Y. Effects of quinidine and related compounds on cytotoxicity and cellular accumulation of vincristine and adriamycin in drug-resistant tumor cells. Cancer Res. 1984 Oct;44(10):4303–4307. [PubMed] [Google Scholar]
- Yusa K., Tsuruo T. Reversal mechanism of multidrug resistance by verapamil: direct binding of verapamil to P-glycoprotein on specific sites and transport of verapamil outward across the plasma membrane of K562/ADM cells. Cancer Res. 1989 Sep 15;49(18):5002–5006. [PubMed] [Google Scholar]