Loading, high-dose fulvestrant regimens do not improve efficacy
MedWire News: Increasing the approved dose of fulvestrant does not appear to improve the efficacy of treatment for recurrent breast cancer, results of a phase II clinical trial indicate.
"Fulvestrant is an estrogen receptor (ER) antagonist that is able to reduce cellular levels of estrogen and progesterone receptors," explain Kathleen Pritchard (University of Toronto, Ontario, Canada) and colleagues.
The drug is licensed at a dose of 250 mg/month (approved dose), but it has been suggested that alternative dosing regimens may improve its efficacy, say the researchers.
To test this theory, Pritchard and team evaluated the efficacy, safety, and pharmacokinetics of three fulvestrant dosing regimens in women with ER-positive, locally advanced/metastatic breast cancer that had relapsed or progressed after prior endocrine therapy.
Patients were randomly assigned to receive the approved dose of fulvestrant (n=47), the approved dose plus a loading dose (500 mg on day 0, 250 mg on days 14, 28, and monthly thereafter, n=51), or a high dose (500 mg/month plus 500 mg on day 14 of month 1, n=46).
The researchers report similar efficacy among the three treatment regimens. Although the objective response rate was numerically lower with the fulvestrant approved dose (8.5%) and loading dose (5.9%) regimens compared with the high dose (15.2%), the difference was not statistically significant.
Similarly, the clinical benefit rate did not differ significantly among the groups, at 31.9%, 47.1%, and 47.8% for the approved, loading, and high doses, respectively.
The median time to progression was longer, at 6.0 and 6.1 months, in the loading, and high-dose groups, respectively, compared with 3.1 months in the approved dose group but the incidence of progression events (31, 34, and 35, respectively) was similar among the groups.
All three fulvestrant dose regimens were well tolerated, with no differences observed between safety profiles among the cohort, note Pritchard et al.
In addition, steady-state plasma fulvestrant concentrations were similar to values determined previously and were achieved by 1 month in the loading and high-dose groups compared with 3 months in the approved dose group.
"The results suggest that there were no major differences in the efficacy, tolerability, and pharmacokinetics of the three fulvestrant dosing regimens," conclude Pritchard and co-authors in the journal Breast Cancer Research and Treatment.
They add that a parallel study reported similar findings in Japanese patients.
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By Laura Dean