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- W1998954673 abstract "Preclinical studies had determined that tamoxifen and interferon-α2b (IFN-α2b) synergistically inhibited growth of both estrogen-receptor positive and negative murine tumor xenografts and had combined antiangiogenic effects and that tamoxifen potentiated IFN-stimulated gene (ISG) expression. A phase I trial in 26 patients was conducted using the combination to define tolerance and potentiation of ISG expression. IFN- α2b at a dose of 3 × 106 units/m2 daily was given subcutaneously (s.c.), and tamoxifen was initiated as a loading dose of 150 mg/m2 and then 60 mg/m2 twice daily on day 8. At this initial dose, reduction of dose of IFN- α2b was required in 4 of 11 patients, primarily because of fatigue. Another group of patients was treated with an identical tamoxifen dose but with IFN-α2b reduced to 2 × 106/m2 U; this was better tolerated. As the projected serum tamoxifen level to reduplicate preclinical effects was 300 mg/m2, dose escalation in a third cohort was undertaken; it had to be discontinued secondary to grade III or IV toxicity in 2 of 2 patients. Increases in products of transcriptionally regulated ISGs, β2-microglobulin, neopterin, and ISG15 were assessed. All ISGs increased after IFN-α2b, but only ISG15 had a further significant rise after initiation of tamoxifen. Because at doses not limited by unacceptable toxicities, no marked potentiation of ISGs by tamoxifen could be identified, clinical evaluation of the combination was terminated." @default.
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- W1998954673 date "2006-11-01" @default.
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- W1998954673 title "Short Communication:Phase I Clinical and Gene Modulatory Evaluation of Tamoxifen and IFN-α2b" @default.
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- W1998954673 doi "https://doi.org/10.1089/jir.2006.26.800" @default.
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