Recommended Dosing Regimen for Fulvestrant in Hormone Receptor-Positive Metastatic Breast Cancer
Fulvestrant should be administered at a dose of 500 mg intramuscularly with a loading schedule (500 mg on days 0,14, and 28, followed by 500 mg every 28 days thereafter) for the treatment of hormone receptor-positive metastatic breast cancer. 1
Dosing Details
- Fulvestrant is administered as two 5 mL injections (250 mg/5 mL each), for a total dose of 500 mg 2
- The loading schedule is critical for achieving therapeutic drug levels more rapidly 3
- The injections should be administered intramuscularly, one in each buttock, slowly 2
- Treatment should continue until there is unequivocal evidence of disease progression as documented by imaging, clinical examination, or disease-related symptoms 1
Evidence Supporting the 500 mg Dose
- The CONFIRM trial demonstrated improved overall survival with the 500 mg dose compared to the 250 mg dose 1
- The 500 mg dose with loading schedule achieves higher steady-state concentrations more rapidly than the 250 mg regimen 3
- Meta-analysis shows significantly improved clinical benefit rate with fulvestrant 500 mg versus comparator treatments (OR 1.33; 95% CI 1.13-1.57; p = 0.001) 4
Clinical Context and Positioning
First-Line Setting
- Aromatase inhibitors (AIs) are generally preferred as first-line endocrine therapy for postmenopausal women with HR-positive MBC 1
- Combination of fulvestrant 500 mg with a nonsteroidal AI may be offered for patients without prior exposure to adjuvant endocrine therapy 1
- Fulvestrant combined with CDK4/6 inhibitors can be offered as first-line therapy in selected patients 1
Second-Line Setting
- Fulvestrant 500 mg with loading schedule is recommended after progression on prior endocrine therapy 1
- Sequential hormone therapy should be offered to patients with endocrine-responsive disease 1
- Fulvestrant and palbociclib may be offered to patients who experienced progression during prior treatment with AIs 1
Special Populations
- For premenopausal women, fulvestrant should be combined with ovarian suppression or ablation 1
- For male patients with HR-positive MBC, fulvestrant should be combined with a gonadotropin-releasing hormone analog 1
Common Pitfalls to Avoid
- Using the outdated 250 mg dose, which is less effective than the 500 mg dose 1, 3
- Omitting the loading schedule, which delays achievement of therapeutic levels 3
- Discontinuing treatment prematurely - treatment should continue until unequivocal disease progression 1
- Using tumor markers or circulating tumor cells as the sole criteria for determining disease progression 1
- Combining fulvestrant with chemotherapy, which is not recommended 1
The 500 mg dose with loading schedule has become the standard of care based on improved efficacy without significant differences in the toxicity profile compared to lower doses 5, 3.