Fosfestrol

Fosfestrol is used as a form of high-dose estrogen therapy in the treatment of castration-resistant prostate cancer.^[2] It is added once progression of metastases has occurred following therapy with other interventions such orchiectomy, gonadotropin-releasing hormone modulators, and nonsteroidal antiandrogens.^[2] Fosfestrol has also been used to prevent the testosterone flare at the start of gonadotropin-releasing hormone agonist therapy in men with prostate cancer.^[9]

Fosfestrol sodium is given at a dosage of 600 to 1200 mg/day by slow intravenous infusion over a period of 1 hour for a treatment duration of 5 to 10 days in men with prostate cancer.^[3][2] Following this, it is given at a dose of 300 mg/day for 10 to 20 days.^[3] Maintenance doses of fosfestrol sodium of 300 to 600 mg may be given four times per week.^[3] This may be gradually reduced to one 300 to 600-mg dose per week over a period of several months.^[3]

Fosfestrol sodium is also used to a lesser extent by oral administration initially at a dosage of 360 to 480 mg three times per day in the treatment of prostate cancer.^[3][2] Maintenance doses of 120 to 240 mg three times per day may be used and can be gradually reduced to 240 mg/day.^[3][2]

Side effects of fosfestrol include nausea and vomiting in 80% of patients (with 1 in 25 cases, or 4%, resulting in death), cardiovascular complications (18% with fosfestrol plus adriamycin relative to 2% with adriamycin alone) such as thrombosis (2 in 25 cases, or 8%), edema (44% requiring diuretic therapy), and skin reactions such as burning, itching, or pain in the genital area (40%).^[2][1] In addition, weight gain, feminization, and gynecomastia may occur.^[1]

Fosfestrol is a synthetic nonsteroidal estrogen of the stilbestrol group.^[15][3] It is an estrogen ester; specifically, it is the diphosphate ester of diethylstilbestrol.^[15][3]

Fosfestrol is provided both as the free base and as a tetrasodium salt.^[2][3] In terms of dose equivalence, 300 mg anhydrous fosfestrol sodium is equal to about 250 mg fosfestrol.^[3]

A polymer of fosfestrol, polydiethylstilbestrol phosphate, was developed as a long-acting estrogen for potential use in veterinary medicine, but was never marketed.^{[16][17][18][19][20][21]}

Fosfestrol was first patented in 1941 and was mentioned in the literature by Huggins.^[6][22] Conjugated estrogens and diethylstilbestrol sulfate, which are water-soluble estrogens, were first reported to be effective in the treatment of prostate cancer via intravenous administration in 1952.^[23][22] Starting in October 1952, Flocks and colleagues studied intravenous fosfestrol in the treatment of prostate cancer, publishing their findings in 1955.^[22] Fosfestrol was first introduced for medical use in 1955 under the brand names Stilphostrol and ST 52 in the United States and France, respectively.^[6]

• Estramustine phosphate