Cancer

Download Aromatase inhibitors by B J A Furr PDF

By B J A Furr

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This could contribute to the combination being rather less effective than letrozole alone. Figure 3. Effects of letrozole and tamoxifen and their combination on the growth of MCF-7CA breast tumour xenografts in female, ovariectomized, athymic nude mice. All mice received androstenedione (100 µg/day sc). Mice were divided into groups (n = 20 per group) and injected subcutaneously daily with vehicle, letrozole (10 µg/day) and/or tamoxifen (100 µg/day). Tumour volumes were measured weekly and are expressed as the percentage change relative to the initial tumour volume.

The selective approach would not interfere with other cytochrome P450 enzymes involved in the synthesis of essential hormones such as cortisol and aldosterone. Thus, selective aromatase inhibition would be a safer and more effective approach than antioestrogens. A number of compounds that are selective inhibitors of aromatase were first reported in 1973 [4]. Model systems for studying aromatase inhibitors in vitro During pregnancy, the placenta expresses high levels of aromatase in the syncytiotrophoblasts in the outer layer of the chorionic villi [5, 6] and is an excellent source of highly active enzyme [4, 7].

After extended treatment, tumours eventually grew during letrozole treatment. However, tumour-doubling time with letrozole was more than twice as long as with tamoxifen. Mice with tumours growing on letrozole treatment were then assigned to three groups so that each had similar mean tumour volumes at the start of second-line treatment. The groups were treated with either tamoxifen, a higher dose of letrozole (100 µg/day), or continued on letrozole (10 µg/day) treatment (Fig. 2) [80]. However, although the higher dose of letrozole slowed tumour growth, tumour volumes were not significantly different from those of groups treated with tamoxifen or continued on letrozole (10 µg/day).

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