Fulvestrant (Faslodex®) is an intramuscularly administered steroidal estrogen receptor antagonist that is devoid of any known estrogen agonist effects. It is indicated as second-line therapy for the treatment of postmenopausal women with hormone receptor-positive advanced breast cancer who have progressed following prior endocrine therapy.

In well designed, randomized clinical trials, regimens of fulvestrant 250 and 500 mg provided effective second-line therapy for postmenopausal women with advanced breast cancer who had progressed following prior endocrine therapy. Moreover, fulvestrant 250 mg monthly (with or without a loading dose) was as effective as aromatase inhibitor therapy. However, fulvestrant is absorbed slowly, and greater steady-state concentrations are achieved more rapidly when using a higher dosage with a loading dose regimen. Consequently, a regimen of fulvestrant 500 mg monthly with a loading dose was significantly more effective than a regimen of 250 mg monthly in postmenopausal women with disease progression. Limited data also indicate a potential role for the fulvestrant 500 mg regimen as first-line therapy.

Fulvestrant is generally well tolerated with no additional adverse events noted with the high-dose regimen compared with the 250 mg regimens. Furthermore, the incidence of joint disorders was shown to be significantly lower with fulvestrant 250 mg monthly than with anastrozole. Treatment with fulvestrant is not associated with any clinically significant effects on endometrial thickening, bonespecific turnover markers or sex hormone levels.

In conclusion, a monthly regimen of intramuscular fulvestrant 500 mg with a loading dose provides effective and well tolerated second-line therapy for postmenopausal women with advanced breast cancer who have progressed following prior endocrine therapy and is now the approved optimal dose.