CN1498112A - Combination therapy for estrogen-dependent disorders - Google Patents
Combination therapy for estrogen-dependent disorders Download PDFInfo
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- CN1498112A CN1498112A CNA018189385A CN01818938A CN1498112A CN 1498112 A CN1498112 A CN 1498112A CN A018189385 A CNA018189385 A CN A018189385A CN 01818938 A CN01818938 A CN 01818938A CN 1498112 A CN1498112 A CN 1498112A
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- cancer
- arimedex
- triptorelin
- lhrh agonist
- exemestane
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
- A61K38/09—Luteinising hormone-releasing hormone [LHRH], i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/32—Antioestrogens
Abstract
The present invention relates to a combination therapy for treating estrogen dependent cancers in susceptible mammals, including humans, comprising the steps of inhibiting hormone output of their testis or ovaries, respectively, and administering to said mammal at least one aromatase inhibitor.
Description
Technical field
The present invention relates to the therapeutic alliance of the mammiferous estrogen dependent cancer disease of susceptible, wherein said mammal comprises the mankind, and described therapeutic alliance comprises that the hormone that suppresses testis or ovary respectively produces and use the step of at least a arimedex to described mammal.
Background technology
Each research worker has been carried out the research of hormonal dependent breast carcinoma and carcinoma of endometrium aspect.Women's endocrine therapy mode is an ovariectomy before a kind of known menopause, is modally undertaken by operation or radiation, and what these two kinds of methods obtained is irreversible castrating.Utilize luteinizing hormone releasing hormone agonist (" LHRH agonist ") to obtain a kind of reversible ovariectomy therapeutic modality, it is by suppressing interstitialcellstimulating hormone (ICSH) (" the LH ") secretion of pituitary gland, serum estrogen can be reduced to (people such as Nicholson on the level of castrating, Brit.J.Cancer39,268-273,1979).
Some studies show that with the LHRH agonist to menopause before the patient with breast cancer treat reacting phase that the reaction brought out and castrating treatment with other form obtained ought (people such as Klijn, J.Steroid Biochem.20,1381,1984; People such as Manni, Endocr.Rev.7:89-94; 1986).
The patent No. is the therapeutic alliance that 4,775,660 United States Patent (USP) relates to women with breast cancer, and wherein said therapeutic alliance is included in after the hormone of blocking its ovary by chemistry or operation method produces, and uses antiandrogen and estrogen antagonist material for this patient.
The patent No. is 4,775,661 United States Patent (USP) relates to the therapeutic alliance of women with breast cancer, wherein said therapeutic alliance is included in after the hormone of blocking its ovary by chemistry or operation method produces, and uses a kind of antiandrogen and selectivity to use a kind of sex steroid biosynthesis inhibitor for this women.
The patent No. is 4,760,053 United States Patent (USP) has been described the treatment to selected sex steroid dependence cancer, and a kind of LHRH agonist of use and/or a kind of antiandrogen and/or a kind of estrogen antagonist material and/or at least a sex steroid biosynthesis inhibitor are united in this treatment.
The patent No. is 4,472,382 U.S. Patent Publication can treat the mammary neoplasms of carcinoma of prostate, benign prostate hyperplasia and hormonal dependent with various LH-RH agonist, and disclose and can treat carcinoma of prostate and optimum hypertrophy with various LHRH agonist and antiandrogen.
The patent No. is 5,550,107 United States Patent (USP) relates to therapeutic alliance women with breast cancer and treatment of endometrial cancer, wherein said therapeutic alliance uses a kind of estrogen antagonist medicine, at least a chemical compound as androgen and progestogen, at least a sex steroid biosynthesis inhibitor and a kind of prolactin antagonist secretion inhibitor of being selected from for this patient after being included in the hormone generation of its ovary of blocking-up.
" goserelin (goserelin) is used for the treatment of the multi-center clinical trial of patient with breast cancer before menopause of hormone receptor positive after the oophorectomize " (J.Clin.Onc.1998 (16): 994-999) of C.W.Taylor, people's such as H.A.Harvey " the LH-RH analog is used for the treatment of human breast cancer ", LHRH and analog thereof-a kind of novel contraceptive and treatment preparation (B.H.Vickery and J.J.Nestor, J., and E.S.E.Hafez, eds) Lancaster, MTPPress, (1984) and " luteinizing hormone releasing hormone analog (buserelin; Buserelin) be used for suffering from before menopause the treatment of metastatic breast cancer " Lancet1 of people such as J.G.M.Klijn, all reported among the 1213-1216 (1982) with three kinds of LHRH agonist-goserelins (goserelin), buserelin (Buserelin) and leuprorelin acetate (leuprolide) are treated some clinical improvementses that the back occurs to the women who suffered from breast carcinoma before menopause.
People such as Stein R.C. are at British Journal of Cancer:62, described among the 679-683 (1990) 4-hydroxyandrostenedione (Formestane formestane) individually and with goserelin (goserelin) when share to the women's that suffered from breast carcinoma before menopause clinical effect with to its endocrine influence.People such as Celio L. are at European Journal of Cancer:S155,691 (on JIUYUE 17th, 1997) and Anticancer Research:19 have described the research among triptorelin (triptorelin) and the 4-hydroxyandrostenedione breast cancer women patient before treating menopause among the 2261-268 (1999).People such as Dowsett M. are at Breast Cancer Researchand Treatment:56, have described in 2435 (1999) with the therapeutic alliance that female patient carried out to breast carcinoma before menopause of R 83842 (vorozole) and goserelin (goserelin).
People such as Tsuchiya N. are at International Journal of ClinicalOncology:(200) described among the 5:183-187 method azoles (fadrazole) and leuprorelin acetate (leuprorelin acetate) to MCF-7 in the effect of cell proliferation.
Order of the present invention is to provide a kind of treatment mammal estrogen dependent cancer disease, the particularly method of sex steroid dependence cancer, and described method does not have the intrusion of operation.
Summary of the invention describes in detail
The invention provides a kind of Therapeutic Method of sex steroid dependence cancer, this method is applicable to the mammal that need carry out such treatment, wherein said mammal comprises the mankind, this method comprised with the dosage that can reach useful therapeutic effect and approaching time gives described mammal simultaneously, use a kind of arimedex and a kind of LHRH agonist or antagonist respectively or sequentially, and wherein, when this cancer is breast carcinoma, and when a) this LHRH agonist is triptorelin (triptorelin), this arimedex is not Formestane (formestane), when b) this agonist is goserelin (goserelin), this arimedex is not R 83842 (vorozole) or Formestane (formestane), when or c) this LHRH agonist was leuprorelin (leuprorelin), this arimedex was not a method azoles (fadrazole).
This people is preferably the women before menopause.
The present invention also provides the application of arimedex in preparing the medicine for the treatment of the mammiferous sex steroid dependence cancer that comprises the people, wherein said mammal just at the same time, accept the treatment of a kind of LHRH agonist or antagonist respectively or sequentially, and wherein, when this cancer is breast carcinoma, and when a) this LHRH agonist is triptorelin (triptorelin), this arimedex is not Formestane (formestane), when b) this agonist is goserelin (goserelin), this arimedex is not R 83842 (vorozole) or Formestane (formestane), when or c) this LHRH agonist was leuprorelin (leuprorelin), this aromatase inhibitor was not a method azoles (fadrazole).
The present invention provides also that a kind of to comprise a kind of arimedex and a kind of LHRH agonist or antagonist be the product of combination formulations, this combination formulations is when therapeutic steroid-dependent cancer, can be simultaneously, the use of difference or order, and wherein, when this cancer is breast carcinoma, and when a) this LHRH agonist is triptorelin (triptorelin), this arimedex is not Formestane (formestane), when b) this agonist is goserelin (goserelin), this arimedex is not R 83842 (vorozole) or Formestane (formestane), when or c) this LHRH agonist was leuprorelin (leuprorelin), this aromatase inhibitor was not a method azoles (fadrazole).
The estrogen dependent cancer disease that can treat with conjoint therapy provided by the present invention is the cancer that is called as " sex steroid dependence cancer " in the prior art.The example of such cancer has carcinoma of testis, carcinoma of prostate, ovarian cancer, cancer of pancreas, uterus carcinoma, coelomic epithelium cancer, sexual cell ovarian cancer, fallopian tube ovarian cancer, breast carcinoma and pulmonary carcinoma.
In one embodiment of the invention, such cancer is the breast carcinoma of women before carcinoma of prostate, ovarian cancer and the breast carcinoma, particularly menopause.
The example of arimedex of the present invention has exemestane (exemestane), Formestane (formestane), method azoles (fadrozole), letrozole (letrozole), R 83842 (zorozole) and anastrozole, preferably exemestane (exemestane), anastrozole and letrozole (letrozole) particularly preferably are exemestane (exemestane).
" arimedex " refers to and comprises single arimedex or two or more, and preferred two kinds, the mixture of arimedex as defined above.Be preferably single arimedex, or one of the component in this mixture is exemestane (exemestane).
The example of LHRH agonist of the present invention is; such as leuprorelin (leuprorelin); deslorelin (deslorelin); triptorelin (triptorelin); buserelin (buserelin); nafarelin (nafarelin); goserelin (goserelin); avorelin; histrelin (histerelin); Compound P TL 03001 (5-oxo-L-propyl group-L-histidyl--L-tryptophanyl-L-seryl--L-tyrosyl--D-tryptophanyl-L-leucyl--L-arginyl--N-ethyl-L-prolineamide (Peptech); compd A N207 (6-[N6-[5-[2-[1; 2; 3; 4; 6; 11-six hydrogen-2; 5; 12-trihydroxy-7-methoxyl group-6; 11-dioxo-4-[[2; 3; 6-three deoxidations-3-(2; 3-dihydro-1H-pyrroles-1-yl) α-L-lyxose-hexose pyrans glycosyl] oxygen]-the 2-naphthacenyl]-1; 5-dioxo amyl group]-D-lysine]-; (2S-cis)-] (ASTA Medica Inc.); compd A N 238L-threonyl amine; N-[5-[2-[(2S; 4S)-1; 2; 3; 4; 6; 11-six hydrogen-2; 5; 12-trihydroxy-7-methoxyl group-6; 11-dioxo-4-[[2; 3; 6-three deoxidations-3-(2; 3-dihydro-1H-pyrroles-1-yl) α-L-lyxose-hexose pyrans glycosyl] oxygen]-the 2-naphthacenyl]-2-oxo ethyoxyl]-1; 5-dioxo amyl group]-D-phenylalanyl-L-cysteinyl--L-tyrosyl--D-tryptophanyl-L-lysyl--L-is valyl-the L-cysteinyl--; ring (27)-disulphide (ASTA Medica Inc.) and compound S PD 424 (LHRH-hydrogel implant) (Shire Pharmaceuticals Group), or their pharmaceutically useful salt.
In one embodiment of the invention, the LHRH agonist is triptorelin (triptorelin) and goserelin (goserelin), or their pharmaceutically useful salt, particularly triptorelin (triptorelin) or its pharmaceutically useful salt.
The example of lhrh antagonist of the present invention is; such as 3: PN: WO0018423 PAGE: 26 claimed protein (cetrorelix); abarelix; ramorelix (ramorelix); teverelix; ganirelix (ganirelix); compd A 75998 (acetyl group-D-(2-naphthyl) alanyl-D-(4-chlorphenyl) alanyl-D-(3-pyridine radicals) alanyl-seryl--(N-methyl) tyrosyl--N6-(nicotinoyl)-D-lysyl--leucyl--N6-(isopropyl) lysyl--propyl group-D-aminopropanamide) and A84861 (oxolane-2-(S)-Ji-carbonyl-glycyl-D-(2-naphthyl) alanyl-D-(4-chlorine) phenylalanyl-D-(3-pyridine radicals)-alanyl-L-(N-methyl) tyrosyl--D-[N6-(3-pyridine radicals carbonyl)] lysyl--L-leucyl--L-(N6-isopropyl) lysyl--L-propyl group-D-aminopropanamide) (Abbot Labs.); GnRH immunogen (Aphton Co.); chemical compound T 98475 (isopropyl 3-(N-benzyl-N-methylamino methyl)-7-(2; the 6-difluorobenzyl)-4; 7-dihydro-2-(4-isobutyryl aminophenyl)-4-oxo thieno [2; 3-b pyridine-5-carboxylate hydrochlorate) (Takeda) and chemical compound MI1544 (acetyl group-D-tryptophanyl-D-cyclopropyl-alanyl-D-tryptophanyl-L-seryl--L tyrosyl--D-lysyl--L-leucyl--L-arginyl--L-propyl group-D-aminopropanamide), or their pharmaceutically useful salt.Typical lhrh antagonist is abarelix or its pharmaceutically useful salt.
The present inventor also finds the arimedex of effective therapeutic dose and effectively the LHRH agonist or the antagonist of therapeutic dose carry out administering drug combinations, above-mentioned sex steroid dependence disease is treated, can produce the independent LHRH agonist or the obtained therapeutic effect of antagonist that are better than only giving effective therapeutic dose.
The more important thing is that they find that toxic action is not accompanied by the therapeutic effect of this new acquisition and produces, toxic action but caused by the arimedex of the effective therapeutic dose of independent use or LHRH agonist or antagonist.
Just as used herein, the connotation of " treatment " refers in particular to " control growth of tumor ", and promptly slow down, interrupt, stop, stop or the formation of reversing tumor, and the complete obiteration that might not show tumor.
Therefore, except that slow down, interrupt, stop, stop or the formation of reversing tumor, will increase the life expectancy that " useful therapeutic effect " also refers to suffer from the individuality of cancer, one or more symptoms of this disease are reduced and/or the quality of life is enhanced.
Medication
When the patient is implemented Therapeutic Method of the present invention, this arimedex and LHRH agonist or antagonist can comprise oral and administration parenteral route so that can be carried out administration by any form or mode that the chemical compound of biological utilisation reaches effective therapeutic dose.
Here used " by administration " or " administration " refer in the medically acceptable any acceptable manner that medicine is given the patient, comprise parenterai administration and oral administration.
" non-intestinal " refers to intravenous administration, subcutaneous administration, intradermal administration or intramuscular administration.
Oral administration comprises with a kind of in this combination formulations component or all carries out administration with the form of suitable for oral administration that the form of wherein said suitable for oral administration has, such as tablet, capsule, suspension, solution, emulsion, powder, syrup or the like.
The administration order of actual preferable methods of the present invention and combination formulations can according to the certain drug preparation of the certain drug preparation of used arimedex, used LHRH agonist or antagonist, the specific sex steroid dependence cancer of being treated and particular patient and other factor of being treated change.
" approaching time " refers in the combinational therapeutic methods of theme of the present invention, and this arimedex can carry out administration simultaneously or carry out administration with any sequence ground with LHRH agonist or antagonist.In a word, used medication can provide the effect of the hormone generation that suppresses mammiferous testis or ovary simultaneously and suppress the effect of aromatase, thereby reaches useful therapeutic effect.
Dosage
The dosage range of combination formulations administration can change according to the situation and the degree of the patient's age and the disease that takes a disease thereof, and can be decided by those skilled in the art.
Therefore, dosage must adapt to the patient situation, react and the actual conditions of the treatment that is associated, this also is the habitual way in all treatments, and the variation that the dosage of being formulated can be according to circumstances and/or adjust according to other clinical setting.
The scope that arimedex suppresses the effective dose of tumor is that each dosage is about 0.5 to about 500mg, and every day, medication was 1-2 time.
For example, method azoles (fadrozole) can be with about 0.5 to about 10mg, particularly with about 1 to about 2mg oral dose administration.For example, letrozole (letrozole) can be with about 0.5 to about 10mg, particularly about 1 to about 2.5mg oral dose administration.For example, Formestane (formestane) can be with about 250mg to about 500mg, and particularly about dosage of 250 to about 300mg carries out parenterai administration.For example, Anastrozole can be with about 0.5 to about 10mg, particularly with about 1 to about 2mg oral dose administration.For example exemestane (exemestane) can every day with about 5mg to about 600mg, particularly about 10 to about 50, more particularly with about 10 to about 25mg oral dose administration, perhaps carries out parenterai administration with about 50 to about 500mg the dosage of per injection.
The effective dose of LHRH agonist or antagonist is the common dose when treating with this compounds.The administering mode that goserelin (goserelin) can adopt is that the goserelin acetate (goserelin acetate) that will slowly discharge goserelin (goserelin) carries out subcutaneous administration, and dosage is about 3 to about 12mg.For example the adoptable administering mode of triptorelin (triptorelin) is to pass through intramuscular administration with the depot formulations form of triptorelin pamoate (triptorelin pamaote), dosage is about 3 to about 20mg, when carrying out administration with this method, each administration has an appointment 1,2,3 or 4 months interval.Especially, triptorelin pamoate (triptorelin pamaote) can be as US 5,225, and 205 and US 5,776, described in 885, carry out intramuscular administration with the form of microgranule, more particularly 1 month depot formulations with 3.75mg carries out intramuscular administration.For example, abarelix can be with the independent intramuscular administration of dosage of per fortnight or slow release every month abarelix 10 to 200mg.
The invention provides the steroid-dependent treatment for cancer method of women before the menopause that a kind of needs carry out such treatment, wherein said sex steroid dependence cancer is selected from ovarian cancer and breast carcinoma, this method comprised with dosage that can reach useful therapeutic effect and approaching time, used exemestane (exemestane) and triptorelin (triptorelin) or their pharmaceutically useful salt in fact simultaneously described women.
" in fact simultaneously " refers to administering mode that exemestane (exemestane) and triptorelin (triptorelin) adopted can provide the hormone generation effect that suppresses patient's ovary and the effect of inhibition aromatase simultaneously, thereby reaches useful therapeutic effect.
As another embodiment of the invention, the present invention also provides the application of exemestane (exemestane) in preparing the medicine for the treatment of women's sex steroid dependence cancer before menopause, wherein said sex steroid dependence cancer is selected from ovarian cancer and breast carcinoma, and wherein said women is accepting to give in fact simultaneously the treatment of triptorelin (triptorelin) or its pharmaceutically useful salt.What treated in one embodiment of the invention is breast carcinoma.
In one embodiment of the invention, exemestane (exemestane) and triptorelin (triptorelin) be the form of embonate particularly, as described, carry out administration with simultaneous system in fact, thereby reaches useful therapeutic effect.
Especially, triptorelin pamoate (triptorelin pamoate) can be with the form of slow releasing preparation by administration, during with this form administration, the interval that each administration was had an appointment 1 to 4 months, for example with as US 5,225,205 and US 5,3.75mg described in 776,885 January depot formulations form carry out administration.Exemestane (exemestane) can carry out parenterai administration with about 50 to about 500mg the dosage of per injection, or with the oral dose administration of every day about 10 to about 25mg.
As mentioned above, the present invention also provides the test kit of the pharmaceutical composition that comprises the therapeutic alliance that is used for above-mentioned selected sex steroid dependence cancer or has packed separately.This test kit or independent packing also comprise the operation instruction of using pharmaceutical composition of the present invention.
As an embodiment, test kit of the present invention can be supplied with non-intestinal compositions and 1 month the depot formulations 3.75mg of triptorelin (triptorelin) of exemestane (exemestane) oral agents 25mg or 50-500mg.
Can be as US 5,225,205 and US 5,776,885 described methods preparations be used for the depot formulations of the pharmaceutical composition that comprises triptorelin pamoate (triptorelin pamoate) of intramuscular administration.
Again for example, can prepare the pharmaceutical composition that comprises exemestane (exemestane) according to US 4,808.616.
All cited in disclosure thing lists of references here all are introduced into as a reference.
Claims (29)
1. the Therapeutic Method of a sex steroid dependence cancer, this method is applicable to the mammal that need carry out such treatment, this method comprises with the dosage that can reach useful therapeutic effect gives described mammal simultaneously, use a kind of arimedex and a kind of LHRH agonist or antagonist respectively or sequentially, and wherein, when this cancer is breast carcinoma, and when a) this LHRH agonist is triptorelin, this arimedex is not a Formestane, when b) this agonist is goserelin, this arimedex is not R 83842 or Formestane, when or c) this LHRH agonist was leuprorelin, this aromatase inhibitor was not a method azoles.
2. the method for claim 1, its neutral steroids dependence cancer is selected from carcinoma of testis, carcinoma of prostate, ovarian cancer, cancer of pancreas, uterus carcinoma, coelomic epithelium cancer, sexual cell ovarian cancer, fallopian tube ovarian cancer, breast carcinoma and pulmonary carcinoma.
3. the method for claim 1, wherein estrogen dependent cancer disease is the breast carcinoma of women before menopause.
4. the method for claim 1, wherein said mammal is the people.
5. the method for claim 1, wherein arimedex is selected from exemestane, Formestane, method azoles, letrozole, R 83842, anastrozole and two or more mixture wherein.
6. the method for claim 1, wherein arimedex is an exemestane.
7. method as claimed in claim 5, wherein, when oral administration, the consumption of arimedex be exemestane about 5 to about 600mg, method azoles about 0.5 to about 10mg, letrozole about 0.5 are to about 10mg, anastrozole about 0.5 is to about 10mg.
8. method as claimed in claim 5, wherein when parenterai administration, the consumption of arimedex is that exemestane about 5 to about 500mg and Formestane about 250 are to about 500mg.
9. the method for claim 1; wherein; the LHRH agonist is selected from leuprorelin; deslorelin; triptorelin; buserelin; nafarelin; goserelin; avorelin; histrelin; Compound P TL 03001 (5-oxo-L-propyl group-L-histidyl--L-tryptophanyl-L-seryl--L-tyrosyl--D-tryptophanyl-L-leucyl--L-arginyl--N-ethyl-L-prolineamide; compd A N 207 (6-[N6-[5-[2-[1; 2; 3; 4; 6; 11-six hydrogen-2; 5; 12-trihydroxy-7-methoxyl group-6; 11-dioxo-4-[[2; 3; 6-three deoxidations-3-(2; 3-dihydro-1H-pyrroles-1-yl) α-L-lyxose-hexose pyrans glycosyl] oxygen]-the 2-naphthacenyl]-1; 5-dioxo amyl group]-D-lysine]-; (2S-cis)-]; compd A N 238 L-threonyl amine; N-[5-[2-[(2S; 4S)-1; 2; 3; 4; 6; 11-six hydrogen-2,5,12-trihydroxy-7-methoxyl group-6; 11-dioxo-4-[[2; 3,6-three deoxidations-3-(2,3-dihydro-1H-pyrroles-1-yl) α-L-lyxose-hexose pyrans glycosyl] oxygen]-the 2-naphthacenyl]-2-oxo ethyoxyl]-1; 5-dioxo amyl group]-D-phenylalanyl-L-cysteinyl--L-tyrosyl--D-tryptophanyl-L-lysyl--L-is valyl-the L-cysteinyl--and, ring (27)-disulphide and compound S PD 424 (LHRH-hydrogel implant) and their pharmaceutically useful salt.
10. the method for claim 1, wherein the LHRH agonist is selected from triptorelin, goserelin and their pharmaceutically useful salt.
11. the method for claim 1, wherein the LHRH agonist is triptorelin or its pharmaceutically useful salt.
12. the method for claim 1, wherein the LHRH agonist is a triptorelin pamoate.
13. the method for claim 1, wherein LHRH agonist triptorelin pamoate is the form of depot formulations, dosage is about 3 to about 20mg.
14. method as claimed in claim 13, wherein, LHRH agonist triptorelin pamoate is 1 month the depot formulations of 3.75mg.
15. the method for claim 1; wherein; lhrh antagonist is selected from 3: PN: WO0018423 PAGE: 26 claimed protein; abarelix; ramorelix; teverelix; ganirelix; compd A 75998 (acetyl group-D-(2-naphthyl) alanyl-D-(4-chlorphenyl) alanyl-D-(3-pyridine radicals) alanyl-seryl--(N-methyl) tyrosyl--N6-(nicotinoyl)-D-lysyl--leucyl--N6-(isopropyl) lysyl--propyl group-D-aminopropanamide) and compd A 84861 (oxolane-2-(S)-Ji-carbonyl-glycyl-D-(2-naphthyl) alanyl-D-(4-chlorine) phenylalanyl-D-(3-pyridine radicals)-alanyl-L-(N-methyl) tyrosyl--D-[N6-(3-pyridine radicals carbonyl)] lysyl--L-leucyl--L-(N6-isopropyl) lysyl--L-propyl group-D-aminopropanamide); the GnRH immunogen; chemical compound T 98475 (isopropyl 3-(N-benzyl-N-methylamino methyl)-7-(2; the 6-difluorobenzyl)-4; 7-dihydro-2-(4-isobutyryl aminophenyl)-4-oxo thieno [2; 3-b pyridine-5-carboxylate hydrochlorate] and chemical compound MI 1544 (acetyl group-D-tryptophanyl-D-cyclopropyl-alanyl-D-tryptophanyl-L-seryl--L tyrosyl--D-lysyl--L-leucyl--L-arginyl--L-propyl group-D-aminopropanamide), and their pharmaceutically useful salt.
16. the Therapeutic Method of a sex steroid dependence cancer, this method is applicable to women before the menopause that need carry out such treatment, wherein said sex steroid dependence cancer is selected from ovarian cancer and breast carcinoma, and this method comprises with the dosage that can reach useful therapeutic effect uses the pharmaceutically useful salt of exemestane and triptorelin or they for described women.
17. method as claimed in claim 16, wherein, this method can provide the hormone generation effect of inhibition female patient ovary and the inhibition/deactivation of aromatase simultaneously, thereby reaches useful therapeutic effect.
18. method as claimed in claim 16, wherein, estrogen dependent cancer disease is a breast carcinoma.
19. method as claimed in claim 16, wherein, triptorelin is the form of triptorelin embonate.
20. method as claimed in claim 16, wherein, triptorelin pamoate is a kind of depot formulations form.
21. method as claimed in claim 16, wherein, triptorelin pamoate is 1 month the depot formulations form of 3.75mg.
22. method as claimed in claim 16, wherein, exemestane oral administration amount is about 5 to 600mg/ days.
23. method as claimed in claim 16, wherein, exemestane oral administration amount is about 10 to 500mg/ days.
24. method as claimed in claim 16, wherein, exemestane oral administration amount is about 25mg/ days.
25. method as claimed in claim 16, wherein, exemestane parenterai administration amount is about 50 to 500mg/ days.
26. the application of arimedex in the medicine of preparation treatment mammal sex steroid dependence cancer, wherein said mammal is being accepted simultaneously, give the treatment of LHRH agonist or antagonist respectively or sequentially, and wherein, when this cancer is breast carcinoma, and when a) this LHRH agonist is triptorelin, this arimedex is not a Formestane, when b) this agonist is goserelin, this arimedex is not R 83842 or Formestane, when or c) this LHRH agonist was leuprorelin, this aromatase inhibitor was not a method azoles.
27. application as claimed in claim 26, wherein, described mammal is the people.
28. application as claimed in claim 26, wherein, arimedex is an exemestane, and the LHRH agonist is a triptorelin, and the sex steroid dependence cancer is ovarian cancer and breast carcinoma.
29. comprising a kind of arimedex and a kind of LHRH agonist or antagonist is the product of combination formulations, this combination formulations is when therapeutic steroid-dependent cancer, can be simultaneously, respectively or the use of order, and wherein, when this cancer is breast carcinoma, and when a) this LHRH agonist is triptorelin, this arimedex is not a Formestane, when b) this agonist is goserelin, this arimedex is not R 83842 or Formestane, when or c) this LHRH agonist was leuprorelin, this arimedex was not a method azoles.
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| US71460500A | 2000-11-16 | 2000-11-16 | |
| US09/714,605 | 2000-11-16 |
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| JP (1) | JP2004536022A (en) |
| KR (1) | KR20030051828A (en) |
| CN (1) | CN1498112A (en) |
| AU (1) | AU2002230464A1 (en) |
| BR (1) | BR0115423A (en) |
| CA (1) | CA2428249A1 (en) |
| CZ (1) | CZ20031349A3 (en) |
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| NO (1) | NO20032206L (en) |
| NZ (1) | NZ525720A (en) |
| PL (1) | PL365904A1 (en) |
| WO (1) | WO2002039995A2 (en) |
| ZA (1) | ZA200303669B (en) |
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| CN101775054B (en) * | 2010-02-05 | 2012-12-26 | 常州佳尔科药业集团有限公司 | Synthesis method of 4-hydroxyl-4-alkene-3-ketone steroide compound |
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| US9050378B2 (en) | 2003-12-10 | 2015-06-09 | Board Of Regents, The University Of Texas System | N2S2 chelate-targeting ligand conjugates |
| GB0506759D0 (en) * | 2005-04-02 | 2005-05-11 | Medical Res Council | Combination treatment methods |
| EP1891964A1 (en) * | 2006-08-08 | 2008-02-27 | AEterna Zentaris GmbH | Application of initial doses of LHRH analogues and maintenance doses of LHRH antagonists for the treatment of hormone-dependent cancers and corresponding pharmaceutical kits |
| US10925977B2 (en) | 2006-10-05 | 2021-02-23 | Ceil>Point, LLC | Efficient synthesis of chelators for nuclear imaging and radiotherapy: compositions and applications |
| JP2010524996A (en) * | 2007-04-23 | 2010-07-22 | バイエル・シエーリング・ファーマ アクチエンゲゼルシャフト | Combination of progesterone receptor antagonists with lutein hormone releasing hormone agonists and antagonists for use in BRCA mediated diseases |
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| GB9911582D0 (en) * | 1999-05-18 | 1999-07-21 | Pharmacia & Upjohn Spa | Combined method of treatment comprising an aromatase inhibitor and a further biologically active compound |
| GB9930839D0 (en) * | 1999-12-30 | 2000-02-16 | Pharmacia & Upjohn Spa | Process for treating gynecomastia |
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- 2001-11-06 CN CNA018189385A patent/CN1498112A/en active Pending
- 2001-11-06 BR BR0115423-0A patent/BR0115423A/en not_active IP Right Cessation
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- 2001-11-06 KR KR10-2003-7006608A patent/KR20030051828A/en not_active Application Discontinuation
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Cited By (1)
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| CN101775054B (en) * | 2010-02-05 | 2012-12-26 | 常州佳尔科药业集团有限公司 | Synthesis method of 4-hydroxyl-4-alkene-3-ketone steroide compound |
Also Published As
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| PL365904A1 (en) | 2005-01-10 |
| IL155817A0 (en) | 2003-12-23 |
| KR20030051828A (en) | 2003-06-25 |
| CZ20031349A3 (en) | 2004-05-12 |
| WO2002039995A9 (en) | 2003-02-06 |
| JP2004536022A (en) | 2004-12-02 |
| CA2428249A1 (en) | 2002-05-23 |
| BR0115423A (en) | 2005-12-13 |
| ZA200303669B (en) | 2004-05-13 |
| NZ525720A (en) | 2006-12-22 |
| EA200300572A1 (en) | 2004-06-24 |
| NO20032206D0 (en) | 2003-05-15 |
| WO2002039995A2 (en) | 2002-05-23 |
| EP1341549A2 (en) | 2003-09-10 |
| MXPA03004195A (en) | 2003-09-22 |
| WO2002039995A3 (en) | 2003-05-01 |
| NO20032206L (en) | 2003-07-15 |
| AU2002230464A1 (en) | 2002-05-27 |
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