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Clinical data | |
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Trade names | Honvan, others |
Other names | Diethylstilbestrol diphosphate; Stilbestrol diphosphate; DESDP; DESP; DES-DP; DES-P |
AHFS/Drugs.com | International Drug Names |
Routes of administration | Intravenous, by mouth |
Drug class | Nonsteroidal estrogen; Estrogen ester |
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ECHA InfoCard | 100.007.573 |
Chemical and physical data | |
Formula | C18H22O8P2 |
Molar mass | 428.314 g·mol−1 |
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Fosfestrol, sold under the brand name Honvan and also known as diethylstilbestrol diphosphate (DESDP), is an estrogen medication which is used in the treatment of prostate cancer in men.[1][2][3] It is given by slow intravenous infusion once per day to once per week or by mouth once per day.[3][2]
Side effects of fosfestrol include nausea and vomiting, cardiovascular complications, blood clots, edema, and genital skin reactions, among others.[2] Fosfestrol is an estrogen, and hence is an agonist of the estrogen receptor, the biological target of estrogens like estradiol.[2][1][4] It acts as a prodrug of diethylstilbestrol.[2][1][5]
Fosfestrol was patented in 1941 and was introduced for medical use in 1955.[6] It was previously marketed widely throughout the world, but now remains available in only a few countries.[7][8][6][3]
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]
Route/form | Estrogen | Dosage | |
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Oral | Estradiol | 1–2 mg 3x/day | |
Conjugated estrogens | 1.25–2.5 mg 3x/day | ||
Ethinylestradiol | 0.15–3 mg/day | ||
Ethinylestradiol sulfonate | 1–2 mg 1x/week | ||
Diethylstilbestrol | 1–3 mg/day | ||
Dienestrol | 5 mg/day | ||
Hexestrol | 5 mg/day | ||
Fosfestrol | 100–480 mg 1–3x/day | ||
Chlorotrianisene | 12–48 mg/day | ||
Quadrosilan | 900 mg/day | ||
Estramustine phosphate | 140–1400 mg/day | ||
Transdermal patch | Estradiol | 2–6x 100 μg/day Scrotal: 1x 100 μg/day | |
IM or SC injection | Estradiol benzoate | 1.66 mg 3x/week | |
Estradiol dipropionate | 5 mg 1x/week | ||
Estradiol valerate | 10–40 mg 1x/1–2 weeks | ||
Estradiol undecylate | 100 mg 1x/4 weeks | ||
Polyestradiol phosphate | Alone: 160–320 mg 1x/4 weeks With oral EE: 40–80 mg 1x/4 weeks | ||
Estrone | 2–4 mg 2–3x/week | ||
IV injection | Fosfestrol | 300–1200 mg 1–7x/week | |
Estramustine phosphate | 240–450 mg/day | ||
Note: Dosages are not necessarily equivalent. Sources: See template. |
Fosfestrol is available in the form of solutions for intravenous administration and tablets for oral administration.[10]
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 an estrogen, or an agonist of the estrogen receptors.[2][1][4] It is inactive itself and acts as a prodrug of diethylstilbestrol.[2][1][5] Similarly to diethylstilbestrol, fosfestrol has powerful antigonadotropic effects and strongly suppresses testosterone levels in men.[2][1][12][13] It decreases testosterone levels into the castrate range within 12 hours of the initiation of therapy.[1] Fosfestrol may also act by other mechanisms, such as via direct cytotoxic effects in the prostate gland.[2][1]
The pharmacokinetics of fosfestrol have been studied.[2][14][1]
See also: Nonsteroidal estrogen, Estrogen ester, and List of estrogen esters § Diethylstilbestrol esters |
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]
Fosfestrol is the generic name of the drug and its INN , BAN , and JAN , while diethylstilbestrol diphosphate is its USAN and fosfestrolo is its DCIT .[15][7][8][3] It is also known as stilbestrol diphosphate.[15][7][8] Fosfestrol sodium is its INNM and BANM .[15][7][8][3]
Brand names of fosfestrol include Cytonal, Difostilben, Honovan, Honvan, Honvol, Honvon, Fosfostilben, Fostrolin, ST 52, Stilbetin, Stilbol, Stilbostatin, Stilphostrol, and Vagestrol, among others.[15][7][8][6]
Fosfestrol has been marketed widely throughout the world, including in the United States, Canada, Europe, Asia, Latin America, and South Africa, among other areas of the world.[7][8][3][6] However, today, it appears to remain available only in a few countries, including Bangladesh, Egypt, India, Oman, and Tunisia.[8][3]