Clinical pharmacology of tamoxifen in patients with breast cancer: comparison of traditional and loading dose schedules.

Tamoxifen blood levels were measured in patients with metastatic breast cancer after single-dose and continuous administration, using a traditional dose schedule of 10 mg/m2 twice daily, a single daily dose schedule of 20 mg/m2; and several loading dose schedules of 20-80 mg/m2 twice daily x 7 days, then a 20-mg/m2 single daily dose thereafter. Using the traditional 10-mg/m2 twice daily schedule, values after continuous administration at the time clinical responses were observed were greater than or equal to 10 x peak values observed after a single dose. Using a loading dose schedule of greater than or equal to 40 mg/m2 twice daily x 7 days, values known to be associated with a response were present by 3 hours, as opposed to greater than or equal to 7 days with the traditional schedule. Levels obtained at peak and trough times with the once-daily schedule suggest tamoxifen may safely be given on a once-daily basis, particularly after the first 8 weeks of therapy. Half-life of tamoxifen after continuous administration is prolonged, and levels obtained for up to 6 weeks after drug discontinuation suggest that false-negative cytoplasmic estrogen receptor (ER) determinations may be obtained if tissue for ER is sampled within 4-6 weeks of prolonged tamoxifen administration.