JPH07188026A - Anticancer agent for hormonal therapy comprising dienogest as effective component - Google Patents

Abstract

PURPOSE:To obtain an anticancer agent for hormonal therapy capable of more strongly inhibiting growth of sex hormone depending cancer cells derived from established human cell line than medroxyprogesterone and tamoxifen in a lower dose than these of the latter two comprising a dienoigest as an effective component. CONSTITUTION:An anticancer agent for hormonal therapy comprising dienogest expressed by the formula, i.e., 17alpha-cyanomethyl-17 beta-hydroxy-estera-4,9 (10)- dien-3-one or its solvent adduct as an effective component. It is preferably useful as a treating agent for sex hormone depending cancer, ulterine cancer and mammary cancer. This anticancer agent has little adverse effect owing to its very low dosage and is can be administered for a long period of time without anxiety owing to its effectiveness at small quantity. Further, its pharmacodynamic effects are expected to be wide.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention is directed to Dienoge
st) or an anticancer agent for hormone therapy characterized by containing a solvate thereof as an active ingredient, a sex hormone-dependent cancer therapeutic agent characterized by containing dienogest or a solvate thereof as an active ingredient, or The present invention relates to a therapeutic agent for endometrial cancer and / or breast cancer, which contains dienogest or a solvate thereof as an active ingredient.

[0002]

BACKGROUND OF THE INVENTION Dienogest has a structure represented by the following formula (I): (17α-cyanomethyl-17β-hydroxy-estra-4,9 (1
(0) -dien-3-one) known international compound (I)
NN).

[0003]

[Chemical 1]

For the properties and the synthetic method of this compound, refer to Schubert et al., Elsevier Science Publishers.
Hen, Natural Products Chemistry ((Natural
Products Chemistry), 1984), pp. 143-158. It is known that dienogest has luteinizing hormone activity, and in recent years, a combination drug with ethinyl estradiol has been manufactured in Germany and has been released as an oral contraceptive. Dienogest is also under development as a therapeutic agent for endometriosis (Experimental Clinical Endocrinology (Exp.
Clin. Endocrinol.), Vol. 94, No. 1-2, page 211, 1989.
So far, so far, no report has been made on the anticancer effect of dienogest. Also, the Geno Guest is
Unlike other compounds with luteinizing hormone activity, it has been reported to have no androgenic effect (Schbert et al., Natural Products Chemistry (Id.)).

As one of the recent research themes of cancer and hormones, "hormone dependence of cancer" in which the hormones of the living body influence the development, growth and progression of cancer.
Is mentioned. In this study, hormone therapy is positioned as an important pillar of drug therapy for endometrial cancer (endometrial cancer), breast cancer, prostate cancer, and thyroid cancer, which are typical sex hormone-dependent cancers. There is. For example, endometrial cancer is more than 95% adenocarcinoma, often retains the character of epithelial cells in the proliferating endometrium, and is thought to develop by estrogen stimulation in the absence of progesterone (Gurpide). , Journal of Natural Cancer Institute (J. Natl.
Cancer Inst.), Vol. 83, No. 6, 405-416, 1991.
Year). Therefore, hormone therapy using an anti-estrogen agent, a luteinizing hormone agent, and the like has been attempted as a drug therapy for endometrial cancer in addition to a general chemotherapeutic agent.

Of these, tamoxifen and its derivatives have been tried as anti-estrogen agents, but it has been reported that these drugs rather enhance the cell proliferation of endometrial cancer cell lines, and the chemistry of breast cancer. It has been reported that long-term administration of tamoxifen as an adjunct to therapy increased the risk of developing endometrial cancer.
The susceptibility of endometrial cancer cells to hormonal agents is not uniform, and therefore efficacy against endometrial cancer has not been established yet (Garpid, Journal of Natural Cancer Institute (ibid)).

On the other hand, 17α-hydroxyprogesterone, megestrol, medrogestone, medroxyprogesterone, etc., which can be orally administered, have been investigated as progestagen agents. Of these, medroxyprogesterone has recently been administered in large doses (400 to 6
00mg) revealed a therapeutic effect on endometrial cancer (Kurihara et al., Obstetrics and Gynecology Practice, Vol. 34, 517).
~ 536, 1985), a high-dose formulation has been developed and put on the market. However, even with a large dose of medroxyprogesterone, the response rate to endometrial cancer
Only 23.6% (Kurihara et al., Obstetrics & Gynecology, same as above). In addition, the side effects of medroxyprogesterone, which are thought to be based on the corticoid action and androgen action, have been regarded as problematic and forced to be used carefully (Okada et al., Obstetrics and Gynecology, Volume 38, No. 4, 575-). 582
Page, 1989).

Further, it is considered that almost all breast cancer and prostate cancer are caused by the action of estrogen and androgen. Also in the drug therapy for breast cancer, hormone therapy using an anti-estrogen agent and a luteinizing hormone agent has been attempted as in the treatment of endometrial cancer. As an anti-estrogen agent, tamoxifen and its derivatives are typical ones, but leukopenia, blood abnormalities such as hypercalcemia, and the risk of developing uterine body cancer due to long-term administration as described above have been reported. It is not always the optimal therapeutic agent. The luteinizing hormone agent includes the above-mentioned medroxyprogesterone, but it also requires a large dose (600 to 1,200 mg per day), which causes side effects that are considered to be based on the corticoid action and androgen action described above. . For prostate cancer, treatment with luteinizing hormone agents in addition to estrogen preparations has been attempted.

Recently, such sex hormone-dependent cancer,
In particular, when a large amount of medroxyprogesterone was administered in the treatment of endometrial cancer and breast cancer, side effects
It has been reported that serious thrombosis occurs in the heart, lungs, etc., and the Safety Division, Pharmaceutical Affairs Bureau, Ministry of Health and Welfare notes that it is necessary to pay sufficient attention to the occurrence of thrombosis when using medroxyprogesterone. Done (Pharmaceutical Research, 23
Vol. 5, p. 664-671, 1992).

[0010]

As described above, in hormone therapy for sex hormone-dependent cancer, a sufficient effective rate has not been obtained at present, and serious side effects are regarded as a problem. In order to more effectively and safely carry out hormone therapy against these cancers in the future, a new type of pharmacological action showing a broader therapeutic effect, including sex hormone-dependent cancers that are difficult to respond to conventional hormone therapy, will be developed. There is an urgent need to develop drugs that have them. Moreover, it has a therapeutic effect at a lower dose, and has less side effects such as thrombosis, coronary heart disease, arteriosclerosis, Cushing's syndrome, or moon face due to androgen action and corticoid action, which conventional hormone therapeutic agents have. Drug development is desired.

[0011]

In view of the above situation, the present inventors have found that they are more effective and more effective than conventional drugs against sex hormone-dependent cancers such as endometrial cancer or breast cancer. At the same time, we have conducted intensive research aiming at a therapeutic drug with few side effects. Finally, they found that dienogest was more potent than medroxyprogesterone and tamoxifen at a much lower dose, suppressing the growth of established human sex hormone-dependent cancer cells. Moreover, dienogest showed a clear inhibitory effect on the growth of established cancer cells in which medroxyprogesterone did not respond at all. And this time, it is newly found that dienogest does not have a corticoid action,
The present invention has been completed by clarifying that the drug has fewer side effects.

[0012] As described above, the present invention is a carcinostatic agent for hormone therapy containing dienogest as an active ingredient, which is expected to be more effective and has fewer side effects than conventional drugs, and a therapeutic agent for sex hormone-dependent cancer containing dienogest as an active ingredient. , An agent for endometrial cancer and / or breast cancer containing dienogest as an active ingredient. The dienogest, which is an active ingredient of the anticancer agent of the present invention, is a compound having a structure of the following formula (I). Also, dienogest is water, ethanol,
It may form solvates with various pharmaceutically acceptable solvents such as glycerol and acetic acid.

[0013]

[Chemical 2]

That is, the present invention is a carcinostatic agent for hormone therapy (a drug for hormone therapy of cancer), which contains dienogest or a solvate thereof as an active ingredient. The present invention also provides a therapeutic agent for sex hormone-dependent cancer, which contains dienogest or a solvate thereof as an active ingredient. Furthermore, the present invention is a therapeutic agent for endometrial cancer and / or breast cancer, which contains dienogest or a solvate thereof as an active ingredient. Furthermore, it is an endometrial cancer therapeutic agent characterized by containing dienogest or a solvate thereof as an active ingredient. In addition, the present invention is a therapeutic agent for breast cancer characterized by containing dienogest or a solvate thereof as an active ingredient. The present invention is also an invention in which dienogest or a solvate thereof is used for producing an anticancer agent for hormone therapy, a therapeutic agent for sex hormone-dependent cancer, a therapeutic agent for endometrial cancer and / or breast cancer. Furthermore, the present invention comprises an anticancer agent for hormone therapy, a sex hormone-dependent cancer therapeutic agent, an endometrial cancer and / or a dienogest or a solvate thereof as an active ingredient.
It is also a method for producing a therapeutic agent for breast cancer.

[0015]

EXAMPLES Next, the effects of the anticancer agent of the present invention will be specifically shown by the following experimental examples. Of the drugs used for comparison,
Medroxyprogesterone can be orally administered similarly to dienogest, and is the only drug approved for endometrial cancer as a hormone therapy drug in Japan.

(Experimental Example 1) Growth-inhibitory effect on human differentiated endometrial cancer-derived cell line (Ishikawa strain): CB-17 skid female mice weighing 17 to 27 g, and human differentiated endometrial cancer-derived cell line. Ishikawa strain (Holinka
(Holinka) et al., Journal of Steroid Biochemistry (J. Steroid Biochem.), Vol. 24, No. 1,
85-89, 1986). After subcutaneously transplanting the cultured cell line into a mouse, and confirming that a cancer having a volume of 1,000 mm ³ or more was formed, the transplanted cancer was excised and finely chopped. It was transplanted subcutaneously on the back.
The drugs shown in Table 1 were administered when the volume of transplanted cancer reached 75 mm ³ or more.

That is, after removing both ovaries of all cases under anesthesia, 5 animals per group were divided into 7 groups (1st group to 7th group).
group). No drug was administered to the 1st group, and 17β was added to the 2nd to 7th groups.
-Estradiol was suspended in physiological saline, and 5 µg per 10 g body weight was intraperitoneally administered every day. Of these, the second group contained a solvent (0.5% carboxymethylcellulose solution, and
5% CMC) is administered as a control group, and 0.5 to 3 to 7 groups.
The test drug dissolved or suspended in% CMC was orally administered at a dose of 0.01 mg / kg to 10 mg / kg for dienogest and at a dose of 100 mg / kg for medroxyprogesterone for 4 weeks every day. After the drug treatment for 4 weeks, the volume of cancer was measured, and the inhibition rate (%) of the used drug against the growth of endometrial cancer cells was calculated by the following calculation formula (A). The results are shown in Table 1.

Table 1 Inhibition rate against cell growth derived from human endometrial cancer cell line (Ishikawa strain) ─────────────────────────────── ──── Group dose Cancer volume inhibition rate (mg / kg body wt / day) (mm ³ ) (%) ──────────────────────── ─────────── Group 1 (no administration) -559-Groups 2 to 7 (administration of estrogen) Control (0.5% CMC) -173330 Dienogest 0.01 750 84 0.1 42 1 112 1 461 108 10 507 104 Medroxyprogesterone 100 916 70 ─────────────────────────────────── * In the table Indicates the average value of the measured values of each group (n =
5).

As is clear from the results shown in Table 1, even when 100 mg / kg of medroxyprogesterone was administered, the inhibition rate against the proliferation of endometrial cancer-derived cells (Ishikawa strain) remained at 70%, whereas that of dienogest. In the administration groups, the proliferation of endometrial cancer-derived cells (Ishikawa strain) was almost completely suppressed at any dose of 0.1 mg / kg or more. Therefore, dienogest had a stronger therapeutic effect on the proliferation of endometrial cancer-derived cells (Ishikawa strain) despite the use of lower doses of 1 / 10,000 to 1/1000 compared to medroxyprogesterone. .

(Experimental Example 2) Growth inhibitory effect on human differentiated endometrial cancer-derived cell line (Hec88-nu strain) CB-17 skid female mice weighing 19 to 28 g, and human differentiated endometrial cancer-derived cell line Hec88-nu strain (Morizawa et al.,
Rinjin Cytology, Vol. 26, No. 3, pp. 433-442, 1987). The growth of Hec88-nu cells is known not to be suppressed by medroxyprogesterone which is a luteinizing hormone agent (Kato et al., Human Cell (Hum. Cell), Vol. 4, No. 2, pp. 165-170, 1991). Using the cells of the culture strain, a transplantation cancer was made subcutaneously in the back of the mouse in the same manner as in Experimental Example 1, and then 40 mg per mouse was transplanted subcutaneously in the back of the mouse to 35 other mice. When the cancer volume reached 75 mm ³ or more, the drugs shown in Table 2 were treated.

That is, the bilateral ovaries of all cases were removed under anesthesia and then divided into groups of 4 to 5 animals (groups 1 to 8). No drug was administered to the first group, and 17β- was given to the second to eighth groups.
Estradiol was suspended in physiological saline, and 5 μg per 10 g body weight was intraperitoneally administered every day. Of these, the second group was administered with a solvent (0.5% CMC) as a control group, and the third to eighth groups were treated with 0.
The test drug dissolved or suspended in 5% CMC was orally administered every day for 4 weeks in the same manner as in Experimental Example 1. After the drug treatment for 4 weeks, the volume of cancer was measured, and endometrial cancer cells (Hec
The rate of inhibition of 88-nu) proliferation was calculated from the above calculation formula (A) as in Experimental Example 1. The results are shown in Table 2.

Table 2 Inhibitory rate against cell proliferation derived from human endometrial cancer cell line (Hec88-nu strain) ───────────────────────────── ──────── Group dose Cancer volume inhibition rate (mg / kg body wt / day) (mm ³ ) (%) ──────────────────── ───────────────── Group 1 (no administration) -595-Groups 2-8 (estrogen administration) Control (0.5% CMC) -17280 Dienogest 0.01 1080 57 0.1 760 85 1 756 686 Medroxyprogesterone 100 1845-10 Tamoxifen 1 1741 1 10 1523 18 18 ────────────────────────── ────────── * The numerical values in the table indicate the average of the measured values of each group (n = 4 or 5).

As is clear from the results shown in Table 2, dienogest suppressed the growth of Hec88-nu cancer cells by 50% or more even at a low dose of 0.01 mg / kg. On the other hand, medroxyprogesterone did not show any cancer growth inhibitory action against Hec88-nu cancer cell proliferation even when administered at 100 mg / kg, as conventionally known. Also, for tamoxifen
Administration of up to 10 mg / kg did not inhibit the growth of Hec88-nu cancer cells. As a result, the antitumor agent of the present invention has a cancer growth inhibitory action mechanism different from conventional luteinizing hormone agents or anti-estrogen agents, and it is speculated that it is effective even for cancers that are difficult to respond to conventional hormone therapy. It was

(Experimental Example 3) Growth inhibitory effect of dienogest on human breast cancer cell line (MCF-7) CB-17 skid female mouse having a body weight of 17 to 25 g, and human breast cancer-derived cell line MCF-7 strain (Soure) (Soule) et al., Journal of Natural Cancer Institute, Vol. 51, 1409-14.
13 pages, 1973). Using the culture cell line,
After transplantation cancer was made subcutaneously in the back of the mouse in the same manner as in Experimental Example 1, 80 mg per mouse was subcutaneously transplanted into the left back in 30 other mice. 0.5 mg / kg / day of 17β-estradiol suspended in physiological saline was intraperitoneally administered to mice every day. When the volume of cancer reached 100 mm ³ or more, it was treated with the following drugs.

That is, after bilateral ovaries of all cases were removed under anesthesia, 5 animals per group were divided into 6 groups (1st group to 6th group).
group). No drug administration to group 1, 17β for groups 2-6
-Estradiol was suspended in physiological saline, and 5 µg per 10 g body weight was intraperitoneally administered every day. Of these, solvent was administered to the second group as a control group, and the test drug dissolved or suspended in 0.5% CMC was added to the third to sixth groups with 0.01 mg of dienogest.
The doses were g / kg to 0.1 mg / kg, medroxyprogesterone was 100 mg / kg, and tamoxifen was 10 mg / kg, which were orally administered daily for 4 weeks. The volume of cancer was measured after the drug treatment for 4 weeks, and the inhibitory rate of the used drug against the growth of breast cancer cells was calculated by the above formula (A) as in Experimental Example 1. The results are shown in Table 3.

Table 3 Inhibition rate against human breast cancer-derived cell proliferation (MCF-7 strain) ─────────────────────────────── ────── Group dose Cancer volume inhibition rate (mg / kg body wt / day) (mm ³ ) (%) ───────────────────── ─────────────── Group 1 (no administration) -88-Groups 2 to 6 (administration of estrogen) Control (0.5% CMC) -462 0 Dienogest 0.01 87 87 100 0.1 79 102 Medroxyprogesterone 100 231 62 Tamoxifen 10 205 205 69 ──────────────────────────────────── ─ * Numerical values in the table indicate the average of the measured values of each group (n =
5).

From the results shown in Table 3, even if 100 mg / kg of medroxyprogesterone or 10 mg / kg of tamoxifen was administered, the proliferation of breast cancer cells could not be sufficiently suppressed. On the other hand, dienogest is 0.01mg / kg-0.1m
g / kg, 1 / for medroxyprogesterone
10,000-1 / 1,000, 1 / 1,000 for tamoxifen
Very small doses of ~ 1/100 almost completely suppressed the proliferation of breast cancer-derived cells (MCF-7). Therefore, dienogest is expected to be significantly superior to conventional drugs not only in endometrial cancer but also in breast cancer and the like.

(Experimental Example 4) Confirmation of the presence or absence of corticoid action in dienogest Male Wistar rats weighing 170 to 210 g were used as one group consisting of 6 rats. After excision of both adrenal glands under anesthesia, the test drug was prepared in the same manner as in Experimental Example 1, and the dose of dienogest was 10 to 100 mg /
Orally administered at a dose of kg once or dissolved in sesame oil, dexamethasone (0.1 mg / kg) or aldosterone (0.0
25 mg / kg) was subcutaneously administered. The same amount of the solvent shown in Table 4 was administered to the control group. Following the test drug treatment, physiological saline (30 ml / kg) was intraperitoneally administered, and then urine was collected for 4 hours, and the urine volume and the urinary electrolyte concentration were measured. As indicators of corticoid action, urine volume and urinary sodium ion / potassium ion excretion ratio (Na / K ratio) were calculated. The results are shown in Table 4.

Table 4 Corticoid action ──────────────────────────────────── Group dose Dose urine Urine Na / K ratio (mg / kg body wt) (ml) P P ─────────────────────────────────── ── Control (0.5% CMC) − 2.4 − 0.78 − Dienogest 10 2.4 NS 0.67 NS 30 2.5 NS 0.91 NS 100 2.7 NS 0.85 NS Dexamethasone 0.1 4.7 <0.01 0.45 <0.01 ───────────── ─────────────────────── Control (sesame oil) − 2.4 − 0.86 − Dexamethasone 0.1 4.5 <0.01 0.41 <0.01 Aldosterone 0.025 1.5 <0.05 0.12 <0.01 ── ────────────────────────────────── * The numerical values in the table represent the average of the measured values of each group. (N =
6). P is the result of analysis of the difference between the mean values of the control group and each group using Dunnett's multiple comparison method. Also, NS means no significant difference.

As is clear from the results shown in Table 4, even when the dienogest was administered at a high dose of 100 mg / kg, there was no difference in urine volume and urinary Na / K ratio from the control group, and it is represented by dexamethasone. Neither the glucocorticoid action nor the mineralocorticoid action represented by aldosterone was observed.

(Experimental example 5) Comparison of androgen action between dienogest and conventional drug Wistar Imado male rats weighing 40 to 60 g per group 5 to 6
Used as an animal. After removing the testicles under anesthesia, the test drug was prepared in the same manner as in Experimental Example 1, and the dose of dienogest was 10 to 100 m.
g / kg dose, and medroxyprogesterone 30-
It was orally administered at a dose of 300 mg / kg. The same amount of solvent (0.5% CMC) was administered to the control group. After daily administration for 7 days,
The ventral prostate was removed and weighed. As an index of the androgenic effect, the increase rate of the average prostate weight of the drug-treated group relative to the average prostate weight of the control group was calculated. The results are shown in Table 5.

Table 5 Androgenic Effect ──────────────────────────────────── Group Dose Prostate Weight Increasing Rate (mg / kg body wt / day) (mg) (%) ──────────────────────────────────── -Control (0.5% CMC) -5.8 100 Dienogest 10 6.2 107 107 30 6.5 112 112 100 6.6 114 Control (0.5% CMC) -6.8 100 Medroxyprogesterone 30 9.2 135 100 100 10. 3 151 300 13.5 199 ──────────────────────────────────── * Numerical values in the table are for each The average value of the measured values of the group is shown (n = 5 or 6).

From the results shown in Table 5, it was confirmed that the dienogest was 100 m
No clear androgenic effect was observed even at high doses of g / kg. On the other hand, medroxyprogesterone increased the prostate weight by 50% or more at a dose of 100 mg / kg or more, and a clear androgenic effect was observed. Based on the above, it was considered that dienogest is far less likely to cause side effects based on androgen action than medroxyprogesterone. It should be noted that the antiestrogenic effect of dienogest is negligible, as described in Schwart et al., Supra, in Natural Products Chemistry.
Products Chemistry, 1984), pages 143 to 158, and taking into consideration the results of Experimental Examples 2 to 3, the effect of the anticancer agent of the present invention cannot be simply explained in terms of anti-estrogen action. Is understood.

From the above experimental results, dienogest exerted an excellent inhibitory effect at an extremely low dose as compared with the conventional drug even in the animal model in which the conventional progestagen or anti-estrogen agent was not effective. From this, the anticancer agent of the present invention is presumed to have a mechanism of action different from that of conventional luteinizing hormone agents or anti-estrogen agents, and is also effective against sex hormone-dependent cancer that is difficult to respond to conventional hormone therapy. It is thought that you can expect. Furthermore, since the anticancer drug of the present invention has almost no androgen action and corticoid action, it is expected to be a safe drug with few side effects such as thrombosis, coronary heart disease, arteriosclerosis, Cushing's syndrome, and moon face. Further, regarding other unknown side effects of the anticancer agent of the present invention, the dose required for the growth prevention of sex hormone-dependent cancer of dienogest shown in the present Experimental Examples 1 to 3 is used as an oral contraceptive drug in Germany. It is a dose that is almost comparable to the clinical dose of the drug (2 mg daily dose), and its safety has been confirmed in clinical trials (2 mg daily dose) as a therapeutic drug for endometriosis. Not considered.

Next, the administration form of the anticancer agent of the present invention will be described. The anticancer agent of the present invention can be administered alone or in combination with other drugs. Specific forms of administration include, for example, tablets, capsules, tablets coated with sugar or coating, granules, fine granules, powders, liquid solutions or suspensions, emulsions, fat emulsions, In the form of ointment,
In addition to being used orally or parenterally, it can be administered rectally or intravaginally as a suppository, and intramuscularly or intravenously as an injection. Further, it may be a sustained-release preparation such as a patch, a tape, or an intradermal implant type. The daily dose for an adult is about 0.05 to 100 mg, preferably 0.5 to 10 mg, and is administered in 1 to 5 divided doses per day.
Both the dose and the administration frequency can be adjusted depending on the body weight, health condition and administration route.

The anticancer agent of the present invention is used in various modes of conventional hormone therapy. That is, in addition to being used alone for sex hormone-dependent cancer, it is used in combination with an existing anticancer drug for hormone therapy, in combination with a chemotherapeutic agent (so-called hormonal chemotherapy), and as adjuvant hormone therapy for surgery. Embodiments are provided for the purpose of preventing, treating or preventing recurrence of the cancer. Examples of the present invention will be shown below. The present invention is not limited to the following examples.

(Example 1) Dienogest 0.5 g Lactose 92.5 g Corn starch 49.0 g Talc 3.0 g Magnesium stearate 5.0 g The above ingredients were appropriately mixed, and 0.50 mg of dienogest per tablet was prepared by a wet granule compression method. Make a 150 mg tablet.

Example 2 Dienogest 2.0 g Lactose 87.0 g Corn starch 6.0 g Magnesium stearate 5.0 g The above ingredients are mixed and 100 mg each is enclosed in a Japanese Pharmacopoeia No. 3 capsule to form a capsule.

(Example 3) Dienogest 1.0 g Polysorbate 80 1.0 g Witepsol (S-55) 98.0 g The above components were kneaded under heating and sealed in a plastic package, and the weight per unit was 1.0. Use as g suppository.

(Example 4) Dienogest 1.0 g Polyoxyethylene lauryl ether 39.0 g Glycerin 20.0 g The above components were melt-kneaded as appropriate and sealed in a package.
Use suppositories with a weight of 1.0 g per unit.

[0041]

EFFECTS OF THE INVENTION In the treatment of sex hormone-dependent cancers such as endometrial cancer and breast cancer, the antitumor agent of the present invention is expected to have a therapeutic effect equivalent to or higher than that of conventional anticancer agents for hormone therapy. it can. Therefore, the side effects of conventional hormone therapy drugs associated with large doses do not pose any problem with this drug. Furthermore, the anticancer agent of the present invention is
It is presumed that it has a mechanism of action different from that of conventional luteinizing hormone agents or anti-estrogen agents, and it can be expected to have a wide range of efficacy even in cases where it did not respond to conventional hormone therapy. The drug of the present invention has extremely high specificity to cancer cells, few side effects, and is effective even in a small amount, so that it can be administered for a long period of time with more peace of mind than conventional drugs.

Front page continued (72) Inventor Yukio Kogi 1-7 Yotsuya, Shinjuku-ku, Tokyo Mochida Pharmaceutical Co., Ltd.

Claims (5)

[Claims] 1. A carcinostatic agent for hormone therapy, which comprises dienogest or a solvate thereof as an active ingredient. 2. A therapeutic agent for sex hormone-dependent cancer, which contains dienogest or a solvate thereof as an active ingredient. 3. Endometrial cancer and / or containing dienogest or a solvate thereof as an active ingredient.
Or a breast cancer therapeutic agent. 4. A therapeutic agent for endometrial cancer, which contains dienogest or a solvate thereof as an active ingredient. 5. A therapeutic agent for breast cancer, which comprises dienogest or a solvate thereof as an active ingredient.