Fulvestrant

Fulvestrant is a prescription drug used to treat certain breast cancers. It is a selective estrogen receptor downregulator (SERD), or pure-anti-estrogen. It was the first SERD to enter the market. SERDs disrupt the activity of the estrogen receptor and prevent the growth of cancerous breast cells. Fulvestrant is different from tamoxifen, the latter being a selective estrogen receptor modulator (SERM). Unlike fulvestrant, SERMs block estrogen receptors in breast tissue but stimulate the receptor in other tissues (such as bone). The Food and Drug Administration approved fulvestrant in April 2002. Fulvestrant is marketed by AstraZeneca under the brand name Faslodex.

Uses

Fulvestrant is used to treat postmenopausal women with breast cancer that expresses the estrogen receptor (hormone receptor positive) and that has spread to other tissues (metastasis). It is used when other treatments (e.g., tamoxifen) have failed.

How Fulvestrant is Taken

Fulvestrant is provided in a solution at a concentration of 50 mg/ml. The recommended dose is 250 mg administered intramuscularly (IM) into the buttock every month.

How Fulvestrant Works

Estrogen receptors are located in numerous tissues. Upon activation, they bind to DNA and initiate the production of proteins (transcription). Overstimulation of these receptors by estrogen in breast tissue leads to the uncontrolled cell growth characteristic of cancer. However, not all breast cancers express the estrogen receptor, and fulvestrant is ineffective in these hormone receptor negative tumors. As a SERD, fulvestrant binds to the estrogen receptor and prevents structural changes that are necessary for the receptor to initiate DNA transcription. Fulvestrant also degrades the receptor, which also reduces DNA transcription.

How the Body Affects Fulvestrant

After injection, circulating levels of fulvestrant peak at about seven days and are maintained over a period of at least one month. Circulating levels reach a steady-state after 3–6 doses. Fulvestrant is metabolized I in the liver by the enzyme CYP3A4. Approximately 90% of fulvestrant is excreted in the feces.

Side Effects

The most common side effects of fulvestrant include the following:

• gastrointestinal symptoms (including nausea, vomiting, constipation, diarrhea and abdominal pain)
• headache
• back pain
• hot flushes
• sore throat

Benefits

Fulvestrant is thought to have a faster onset of action and better safety profile than SERMs such as tamoxifen because of its selective blocking of estrogen receptors in the breast. In addition, fulvestrant may have a longer duration of action than does tamoxifen for which resistance to treatment can develop after five years.

Risks and Precautions

Fulvestrant can harm the fetus, and therefore its use during pregnancy places a high risk to the developing baby.

Drug Interactions

To date, no significant drug interactions with fulvestrant have been reported.

Research

The standard treatment for hormone receptor positive breast cancer following surgery is tamoxifen. However, after five years other treatments may need to be sought. Fulvestrant is one option. Another approach is the use of aromatase inhibitors such as anastrozole (Arimidex). Aromatase inhibitors prevent the synthesis of estrogen rather than effect the estrogen receptor directly.

Research

The effectiveness of fulvestrant and anastrozole were compared in a North American study of 400 postmenopausal women with advanced breast cancer for whom the cancer progressed despite prior treatment.^[1] The time to disease progression in both treatment groups was similar, 5.4 months for fulvestrant and 3.4 months for anastrozole. Clinical benefits were seen in 42% and 36% of patients receiving fulvestrant and anastrozole, respectively. The duration of response was slightly greater for fulvestrant.

References

1. ↑ Osborne CK, Pippen J, Jones SE, pri A, et al. Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. J Clin Oncol. 2002 Aug 15;20(16):3386-95. Abstract | Full Text | PDF

External Links

FDA: Patient Information Sheet

Drugs.com