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Combination of | |
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Estradiol valerate | Estrogen |
Gestonorone caproate | Progestogen |
Clinical data | |
Other names | EV/GC; EV/NOHPC; EV/OHNPC; SH-834; SH-8.0834 |
Routes of administration | Intramuscular injection |
Estradiol valerate/gestonorone caproate (EV/GC), known by the developmental code names SH-834 and SH-8.0834, is a high-dose combination medicationofestradiol valerate (EV), an estrogen, and gestonorone caproate (GC; norhydroxyprogesterone caproate), a progestin, which was developed and studied by Schering in the 1960s and 1970s for potential use in the treatment of breast cancer in women but was ultimately never marketed.[1][2][3][4][5][6][7] It contained 90 mg EV and 300 mg GC in each 3 mL of oil solution and was intended for use by intramuscular injection once a week.[3][6] The combination has also been studied incidentally in the treatment of ovarian cancer.[8]
Both high-dose estrogens and high-dose progestogens have been found to be independently effective in the treatment of breast cancer in women.[6][9][10] High-dose estrogens show greater and more consistent effectiveness than high-dose progestogens for this indication.[6][9][11] The combination of an estrogen and progestogen, specifically estradiol benzoate and progesterone, was first studied in breast cancer in rodents and women by Charles Huggins and colleagues in 1962.[9][6][12][11] Initially progesterone and hydroxyprogesterone caproate were used as the progestogen component in such studies;[6][12][13] the need for a more potent progestogen in such combinations led to the development of EV/GC, which was first reported in the treatment of breast cancer in women in 1966.[6][1] GC is a relatively pure progestogen that has about 5- to 10-fold the progestogenic potency of hydroxyprogesterone caproate in humans.[14][15][16] New reports on EV/GC in breast cancer continued until 1976.[7]
Both progesterone and hydroxyprogesterone caproate, which are relatively pure progestogens, have been found to have modest or negligible effectiveness when employed by themselves in the treatment of breast cancer in women.[9][11][17][18][19] Conversely, progestins with off-target glucocorticoid and/or androgenic activity, such as medroxyprogesterone acetate, megestrol acetate, and 19-nortestosterone derivatives, have been found to have greater and more clinically useful effectiveness in comparison.[9][10] This has raised the possibility that the beneficial therapeutic effects of progestogens in breast cancer may be more related to their off-target activity than their progestogenic activity.[9] In accordance, a study found that the effectiveness of an estrogen alone and the combination of EV/GC in the treatment of breast cancer in women was not significantly different.[7] This was the last study of EV/GC to be published.[7]
Progesterone in the Treatment of Advanced Tumours of the Breast. The clinical trial with a progestogen/oestrogen compound, Trial No. SH 834 has been continued. An assessment of its effectiveness in 25 patients with advanced cancer of the breast, of whom 8 were in a terminal stage of the disease and in almost all of whom other types of treatment had failed or become ineffective, has been made. In the group of 8 terminal cases only 2 showed a temporary improvement. Of the remaining 17 cases with treatment periods up to 10 months 16 are still alive; in 9 cases the results were good and in 7 of these, after other measures had failed, SH 834 brought about a temporary arrest of the disease with considerable, though incomplete, regression of the skin infiltrations and amelioration of the general condition and well-being of the patients.
Gestonorone caproate is a depot gestagen, five times more potent than 17α-hydroxyprogesterone caproate.
The preparations used were Proluton Depot (17a-hydroxy-progesterone caproate) and in 3 patients SH 5132 (17a-hydroxy-19-norprogesterone caproate); 100 mg of the latter corresponds to 1000 mg of Proluton Depot.
Thirteen patients with primary adenocarcinoma of the uterine corpus were treated for 21 days with 17alpha-hydroxy-progesterone-caproate (Primolut Depot®, Schering), 1000 mg daily, or 17alpha-hydroxy-19-nor-progesterone-caproate (Depostat®, Schering), 200 mg daily. These doses can be considered as equivalent.
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Progestogens (and progestins) |
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Antiprogestogens |
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ERTooltip Estrogen receptor |
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GPERTooltip G protein-coupled estrogen receptor |
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PRTooltip Progesterone receptor |
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mPRTooltip Membrane progesterone receptor (PAQRTooltip Progestin and adipoQ receptor) |
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