Breast cancer – fulvestrant
As breast cancer is largely hormone dependent, drugs that antagonise or inhibit oestrogen can be very effective treatments, as they remove the hormone that the tumour requires to grow.
The drug tamoxifen has found widespread use in the treatment of breast cancer, both as a primary agent in metastatic cancer and as a preventative measure, as it acts as a competitive antagonist for oestrogen in the breast. However, because it acts like an oestrogen, it does have several undesirable side-effects, such as endometrial stimulation, vasomotor effects, cancer and tumour flare.
A newer drug in the late stages of development at AstraZeneca, fulvestrant, does not cause these side-effects, as it has no oestrogen-like activity1. The oestradiol derivative has a binding affinity for oestrogen receptors similar to that of oestradiol, and around a hundred times stronger than tamoxifen. It is able to downregulate the oestrogen receptors by as much as 90%, and almost no oestrogen receptors are found in breast tissue after a few weeks of treatment with the compound. Other activities include a weak antiprogestin effect, and an ability to modulate apoptosis induction.
Comparative trials using fulvestrant and the aromatase inhibitor anastrazole in patients with tamoxifen-resistant tumours have been carried out. The patients, who were post-menopausal and had advanced breast cancer, were given 125mg or 250mg of fulvestrant, or 1mg of anastrazole. The trials showed that the two drugs gave a similar time to progression for the disease, but one indicated that the median response duration could be substantially longer for fulvestrant. The incidence of side-effects was low, with the main problems noted being hot flushes and gastrointestinal disturbances.
Other trials are under way, notably comparing fulvestrant with tamoxifen in metastatic breast cancer in a placebo controlled trial. The drug has been submitted for approval by the FDA as a treatment for metastatic or locally advanced breast cancer in previously hormone treated women, and it could well prove to be a significant advance in the treatment of this disease.