Abstract
Drug resistance is a common phenomenon in clinical oncology. In vitro, tamoxifen has been shown to be an effective inhibitor of P-glycoprotein and a modulator of the multidrug resistance phenotype. We have previously shown that vinblastine can be given safely in combination with tamoxifen at doses that may modulate P-glycoprotein activity. In this phase I trial, tamoxifen (150 mg/m2 twice a day) was given with CHOPE (cyclophosphamide/doxorubicin/vincristine/prednisone/etoposide) in order to assess the toxicities of the combination. Resistance to three of these cytotoxic agents (doxorubicin, vincristine, and etoposide) may be mediated by P-glycoprotein. A total of 13 patients were evaluable on this trial, which showed that the maximum tolerated doses of cyclophosphamide and etoposide were 750 and 80 mg/m2, respectively. The dose-limiting toxicity was myelosuppression with 50% of the patients (3/6) treated at this dose level developing febrile neutropenia and 85% (6/7) developing grade 4 neutropenia. Tamoxifen at a dose of 150 mg/m2 twice a day can be given safely with the lymphoma regimen CHOPE at standard doses, but his combination may result in increased myelosuppression.
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Supported in part by grants 5T32-CA-09307 and P30-A-14236-18 from the National Institutes of Healthand the National Cancer Institute, the P. B. Cohen Memorial Fund, and ICI Pharmaceuticals, Inc.
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Smith, D.C., Trump, D.L. A phase I trial of high-dose oral tamoxifen and CHOPE. Cancer Chemother. Pharmacol. 36, 65–68 (1995). https://doi.org/10.1007/BF00685734
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DOI: https://doi.org/10.1007/BF00685734