JP2009067737A - Therapeutic and/or prophylactic agent for lower urinary tract symptom after radiation therapy - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a prophylactic and/or a therapeutic agent for prophylaxis, alleviation or relief of LUTS (lower urinary tract symptoms) after radiation therapy. <P>SOLUTION: The prophylactic and/or the therapeutic agent for the LUTS after therapy with sealed small radioactive sources comprises silodosin or a pharmacologically acceptable salt thereof or a solvate thereof as an active ingredient. The silodosin formulation has the silodosin or the pharmacologically acceptable salt thereof or the solvate thereof in an amount effective for the LUTS after the therapy with the sealed small radioactive sources for combined use with the therapy with the sealed small radioactive sources. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a therapeutic and / or prophylactic agent for lower urinary tract symptoms (LUTS) after radiation therapy.

  Brachytherapy, a brachytherapy method that seals the radiation source, inserts it into the prostate, and places it in place, has been performed for more than a decade in the United States, and has already been established as a general treatment for prostate cancer. Has been. As the number of early prostate cancers increases, the number of patients treated with iodine-125 (I-125) brachytherapy has increased remarkably in Japan.

However, in this treatment, there is a high incidence of lower urinary tract symptoms (LUTS) due to physical urinary pressure due to transient swelling and hematoma of the prostate due to radiation therapy, and irritation of the prostate urethral mucosa. Allowed to rate. For example, Lee et al. Found that 31 patients who received brachytherapy with I-125 alone had an international prostate symptom score (IPSS score) that was more than doubled 1 month after treatment and exceeded baseline for 12 months. (Non-Patent Document 1: Lee WR, et al. Int J Radiat Oncol
Biol Phys. 46: 77-81, 2001). Al-Booz et al. Also found that in 50 cases who received brachytherapy with I-125 alone, all cases experienced dysuria more than 3 to 6% within 3 to 6 months after treatment. After confirming that moderate frequent urination and moderate dysuria were observed in 18%, it was reported that this symptom improved within 18 months (Non-Patent Document 2: Al-Booz H, et al BJU Int. 83: 53-56,1999). Similarly, Henderson et al. Have reported that 90% of them are aware of some dysuria after brachytherapy and are maximal 6 weeks after treatment. In addition, the entire cohort has 9 months until IPSS and IPSS Bother scores return to baseline (Non-patent Document 3: Henderson A et al. BJU Int. 90: 567-572, 2002).

  Thus, although brachytherapy is effective as a treatment method for early prostate cancer, it has been reported that LUTS exacerbates after therapy and the incidence of dysuria is maximized in the months after treatment. Therefore, establishment of symptomatic treatment has been desired.

The effectiveness of α ₁ receptor blockers has been investigated for the purpose of improving and suppressing postoperative urinary tract complications in brachytherapy. As the first study to examine this, Merrick et al. Showed that urinary function in patients who received tamsulosin hydrochloride, an α ₁ receptor blocker, before and after brachytherapy was earlier than in the control group. (Median 6 weeks) that it recovered to the baseline (Non-Patent Document 4: Merrick GS, et al. Int J Radiat
Oncol Biol Phys. 47: 121-128,2000). In the subsequent studies, a comparative study was conducted between the prophylactic α ₁ receptor blocker administration group (administration before treatment), the symptom onset group, and the α ₁ receptor blocker non-administration group. It was confirmed that the recovery to the baseline of IPSS was excellent in the non-patent document 5 (Merrick GS, et al. Urology. 60: 650-655, 2002). Multivariate analysis also confirms that prophylactic α ₁ receptor blocker administration is associated as an independent factor that facilitates earlier improvements to the baseline of IPSS. However, even with prophylactic α ₁ receptor blockers, 80% of cases still needed treatment after recovering to baseline. In addition, the effectiveness of the treatment for lower urinary tract irritation that occurs most frequently after radiotherapy has not yet been clarified.

On the other hand, (-)-(R) -1- (3-hydroxypropyl) -5- [2-[[2- [2- (2,2,2-trifluoroethoxy) phenoxy] ethyl] amino] propyl] Indoline-7-carboxamide (generic name: silodosin) is an indoline derivative developed as a therapeutic agent for dysuria having a selective inhibitory effect on urethral smooth muscle contraction having a high affinity for the α _1A receptor ( Patent Document 1: Japanese Patent Laid-Open No. 6-220015, Patent Document 2: Japanese Patent Laid-Open No. 2000-247998). Here, α _1A receptor is a subtype of α ₁ receptor, and silodosin has high selectivity for α _1A receptor. For example, tamsulosin hydrochloride and naphthopidyl have α _1A receptor selectivity of 10 times or less and 1 time or less, respectively, with respect to α ₁ receptors of other subtypes (α _1B receptor and α _1D receptor). In contrast, silodosin exhibits a high α _1A receptor selectivity of several tens to a hundred times or more (for example, Non-patent Document 6: Tachimichi Kaoru et al., Pharmaceutical Journal, 2006; 126: 209-216). However, silodosin is not known to have an effect on lower urinary tract symptoms (LUTS) after radiation therapy. In addition, in the latest knowledge, it has been reported that α _1D receptors among α ₁ receptor subtypes are widely distributed in bladder detrusor muscle, which is considered to be related to lower urinary tract symptoms after radiotherapy, The effect of silodosin on lower urinary tract symptoms after radiotherapy was not expected.

JP-A-6-220015 JP 2000-247998 Lee WR, et al. Int J RadiatOncol Biol Phys. 46: 77-81,2001 Al-Booz H, et al. BJU Int. 83: 53-56,1999 Henderson A et al. BJU Int. 90: 567-572,2002 Merrick GS, et al. Int J RadiatOncol Biol Phys. 47: 121-128,2000 Merrick GS, et al. Urology. 60: 650-655,2002 Merrick GS, et al. Urology. 60: 650-655,2002 Tachimichi Tatsumi et al., Pharmaceutical Journal, 2006; 126: 209-216

  An object of the present invention is to provide a preventive and / or therapeutic agent for preventing, reducing or eliminating lower urinary tract symptoms (LUTS) after radiotherapy.

We have α ₁
The relationship between receptor subtypes and lower urinary tract symptoms after radiation therapy has been investigated (eg Urology. 68: 1230-1236, 2006). And as a result of further investigation, it was found that silodosin is effective in improving lower urinary tract symptoms after radiotherapy despite showing high selectivity for α _1A receptor over α _1D receptor, The present invention has been completed. That is, the present invention provides the following preventive and / or therapeutic agents for lower urinary tract symptoms after brachytherapy, silodosin preparations and methods for administration thereof.

1. A prophylactic and / or therapeutic agent for lower urinary tract symptoms after brachytherapy, comprising silodosin or a pharmacologically acceptable salt thereof or a solvate thereof as an active ingredient.
2. The therapeutic and / or prophylactic agent according to claim 1 in brachytherapy using I-125 as a radiation source.
3. To be used in combination with brachytherapy, which contains silodosin or a pharmacologically acceptable salt thereof or a solvate thereof in an effective amount for lower urinary tract symptoms after brachytherapy Silodosin formulation.
4). 4. The silodosin formulation according to 3 above for use in combination with brachytherapy using I-125 as a radiation source.
5). 0.1-100 mg per day for adults or 0.01-100 mg per day for adults parenterally, or a pharmacologically acceptable salt thereof, or a solvate thereof, for brachytherapy A method for administering a silodosin preparation, which is administered before and / or after.
6). After starting brachytherapy, silodosin or a pharmacologically acceptable salt thereof or a solvate thereof within a range of 0.1 to 50 mg per dose, 1 to 3 times a day for at least 3 months A method for administering a silodosin preparation, characterized by being orally administered over a period of time.
7). QOL improvement in the treatment of early prostate cancer characterized by administering a silodosin preparation containing silodosin or a pharmacologically acceptable salt thereof or a solvate thereof as an active ingredient after initiation of brachytherapy Method.
8). A method for treating early prostate cancer, comprising a combination of brachytherapy and administration of a silodosin preparation containing silodosin or a pharmacologically acceptable salt thereof or a solvate thereof as an active ingredient.

  The preventive and / or therapeutic agent of the present invention is effective in improving and preventing lower urinary tract symptoms after radiation therapy, for example, various symptoms such as feeling of residual urine, dysuria and incontinence.

Silodosin contained as an active ingredient in the preventive and / or therapeutic agent for lower urinary tract symptoms after brachytherapy of the present invention has the following chemical formula (-)-(R) -1- (3-hydroxypropyl) ) -5- [2-[[2- [2- (2,2,2-trifluoroethoxy) phenoxy] ethyl] amino] propyl] indoline-7-carboxamide.

Silodosin can be produced, for example, by the method described in Patent Document 1 and the like.
The compound contained as an active ingredient in the lower urinary tract symptom after brachytherapy of the present invention may remain as the above free form or may be used as a pharmacologically acceptable salt. Examples of pharmacologically acceptable salts include hydrochloric acid, hydrobromic acid, sulfuric acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, acetic acid, citric acid, succinic acid, tartaric acid, 2,4- Dimethylbenzenesulfonic acid, 2,5-dimethylbenzenesulfonic acid, 2,4,6-trimethylbenzenesulfonic acid, (+)-camphorsulfonic acid, (-)-camphorsulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalene Examples thereof include mono- or diacid addition salts with sulfonic acid, 1-butanesulfonic acid, fumaric acid, glutamic acid, aspartic acid and the like. In addition to the above-mentioned free form and salt, these solvates may be used. Examples of solvates include hydrates and ethanol, but also include solvates with other pharmaceutically acceptable solvents.

Further, the brachytherapy to which the present invention can be applied is not particularly limited as long as the brachytherapy is applied to the prostate.
Sealed brachytherapy is a method in which a radiation source is sealed in a container and inserted into the prostate.In general, the radiation source is permanently inserted into the container, but temporarily inserted into the body and then removed. It may be taken. Alternatively, the radiation source may be permanently inserted into the patient's body and attenuated to an inactive state after an expected time. Whether it is a temporary or permanent insertion is determined by the radiation selected, the duration of the treatment required and its intensity.

In a typical protocol for brachytherapy, a low-dose-rate radiation substance such as iodine-125 (I-125) (half-life of 59.4 days) is inserted transperineally and is continuously irradiated from within the prostate. It is a method that aims at radical cure. Specifically, prostate image information captured from a transrectal ultrasound probe is captured in treatment planning software, and the optimal arrangement of the radiation source is calculated using the computer. Based on the results of the treatment plan, a puncture needle is inserted transperineally, and a radiation source is inserted into the prostate using a mimic applicator. Usually, about 60 to 100 radiation sources are applied to the patient. Used per person.

Currently commercially available radioactive sources take the form of capsules encapsulating radioactive isotopes. These radioactive source capsules are formed from a biocompatible material such as titanium or stainless steel and are sealed to prevent radioisotope leaching. The capsule is sized to fit under one hole of a needle used in the insertion device. Since most such needles are about 18 gauge, capsules typically have a diameter of about 0.8 mm and a length of about 4.5 mm. The most commonly used radioisotope for prostate brachytherapy is iodine 125 (I-125). This emits low energy radiation and has a half-life on the order of 60 days, so at a typical starting dose, its radioactivity is almost depleted after 10 months.

However, the present invention does not rely on a specific protocol in brachytherapy. For example, other radioisotopes can be used as the radioisotope. An example of another radioisotope is palladium 103 (Pd-103). Since Pd-103 has a half-life of about 17 days, it is almost inactive after 3 months. Radioactive capsules may also be formed of non-metallic biocompatible materials, such as polymers, polyhydroxy acids (polylactic acid, polyglycol-lactic acid), polyanhydrides (poly (bis (p-carboxy) Phenoxy) propane anhydride, poly (bis (p-carboxy) methane anhydride), copolymers of polycarboxyphenoxypropane and sebacic acid, polyorthoesters, polyhydroxyalkanoates (polyhydroxybutyric acid), and poly (isobutyl) Biodegradable polymers such as cyanoacrylate may be used, and the radioactive source need not be a capsule containing a single radioactive source, but may be a structure in which a plurality of radioactive sources are arranged at appropriate intervals.

The preventive and / or therapeutic agent for lower urinary tract symptoms after brachytherapy according to the present invention containing silodosin or a pharmacologically acceptable salt thereof or a solvate thereof as an active ingredient can be administered orally. It may be administered parenterally. The dosage form can be used in various forms depending on the usage, for example, oral administration such as powder, granule, fine granule, dry syrup, tablet, capsule, injection, patch, suppository, etc. Parenteral administration agents can be mentioned.

These preventive and / or therapeutic agents are prepared according to the method used in pharmacology depending on the dosage form, and suitable excipients, disintegrants, binders, lubricants, diluents, buffers, isotonic agents. It can be produced by mixing or diluting / dissolving with pharmaceutical additives such as preservatives, wetting agents, emulsifiers, dispersants, stabilizers, solubilizers, etc., as appropriate, and dispensing according to conventional methods.

For example, a powder can be produced by mixing an active ingredient such as silodosin or a pharmacologically acceptable salt thereof with an appropriate excipient or lubricant as necessary. Tablets are made into tablets by adding conventional excipients, disintegrants, binders, lubricants and the like to silodosin or a pharmacologically acceptable salt thereof, if necessary, according to a conventional method. If necessary, it may be coated to form a film-coated tablet, a sugar-coated tablet, or the like. Capsules are mixed with silodosin or a pharmacologically acceptable salt thereof by adding an appropriate excipient, lubricant, etc., if necessary, and then filled into an appropriate capsule to form a capsule. Further, it may be filled after it is made into granules or fine particles by a conventional method, or after adding a dispersant, an emulsifier, a stabilizer, a solubilizing agent, etc. to make it liquid.

Moreover, the preventive and / or therapeutic agent of the present invention may be a sustained-release preparation. For example, a matrix-type sustained-release preparation in which a sustained-release base is blended in a tablet or granule as a normal sustained-release preparation, or a tablet, granule or matrix-type sustained-release preparation obtained by a conventional method It can be orally administered as a film-controlled sustained-release preparation coated with an agent. Sustained release bases include hardened oil, stearyl alcohol, cetyl alcohol, paraffin, fatty acid monoglycerin and other waxes, hydroxypropylmethylcellulose, hydroxypropylcellulose, ethylcellulose, carboxyvinyl polymer, vinyl acetate resin, ethyl acrylate methyl methacrylate Mention may be made of copolymers, aminoalkyl methacrylate copolymers, methacrylic acid copolymers and the like.

Therefore, according to the present invention, a sealed composition comprising silodosin or a pharmacologically acceptable salt thereof or a solvate thereof in an effective amount for lower urinary tract symptoms after sealed brachytherapy. A silodosin formulation for use in combination with brachytherapy is provided. Here, the effective amount may vary depending on the dosage form, the subject patient, etc., but orally, generally 0.1-100 mg per day for adults, parenterally, generally 0.01-100 mg per day for adults The content is such that it can be administered within the range.
When the preparation of the present invention is used for the prevention of lower urinary tract symptoms after brachytherapy, the administration is started, for example, before or immediately after the treatment in accordance with the brachytherapy.
In addition, the preparation of the present invention may be used for treatment when lower urinary tract symptoms are confirmed after sealed brachytherapy.

The dose is appropriately determined depending on the sex, age, weight, symptom, etc. of the subject patient.For example, when silodosin or a pharmacologically acceptable salt thereof is used as an active ingredient, it is generally orally. It is administered in the range of 0.1-100 mg per day for adults and parenterally, generally 0.01-100 mg per day for adults. However, these are guidelines and administration outside this range is possible.
Therefore, according to the present invention, for example, after starting brachytherapy, silodosin or a pharmacologically acceptable salt thereof or a solvate thereof within a range of 0.1 to 50 mg per dose is used. There is provided a method for administering a silodosin preparation characterized in that it is orally administered 1 to 3 times a day for at least 3 months, preferably 6 months or more.
By administering such a silodosin preparation, improvement of QOL or the like is realized in the treatment of early prostate cancer.
Therefore, according to the present invention, after starting brachytherapy, administration of a silodosin preparation containing silodosin or a pharmacologically acceptable salt thereof or a solvate thereof as an active ingredient is performed. A method for improving QOL in early prostate cancer treatment is provided.
A method for treating early stage prostate cancer, comprising a combination of brachytherapy and administration of silodosin preparation containing silodosin or a pharmacologically acceptable salt thereof or a solvate thereof as an active ingredient Is provided.

  Hereinafter, the present invention will be described with reference to examples. The following examples are given to illustrate the present invention and are not intended to limit the present invention. The test conditions and evaluation methods of the examples and comparative examples are as follows.

[subject]
I-125 Targeted 249 low-risk group prostate cancer patients receiving brachytherapy (serum PSA less than 10.0 ng / ml, T2a or less, Gleason sum 7 or less: silodosin 53 cases, tamsulosin hydrochloride 120 cases, naphthopidyl 48 cases). Prior to this clinical study, we received approval from the Ethics Committee and obtained written consent from the patients themselves. None of the subjects had undergone other LUTS improvement therapies such as neoadjuvant hormone therapy or received external radiation. In addition, for the evaluation of effectiveness, it has not received administration that affects urination.

[Drug]
The silodosin formulation was orally administered twice daily after meals, with an 8 mg amount taken as a daily dose of Kurisei Pharmaceutical Co., Ltd. Urief (registered trademark) capsules.
As a comparative preparation, tamsulosin hydrochloride (generic name; Harnal (registered trademark) manufactured by Astellas Pharma Inc.) was used as a daily dose, and 0.2 mg was orally administered once a day after breakfast.
In addition, naphthopidyl (generic name: Organon Avishot) was taken as a daily dose, and 75 mg was orally administered three times a day after each meal.

[Evaluation methods]
I-125 Evaluation by International Prostate Symptom Score (IPSS) and evaluation of urinary flow change by urofluometry before brachytherapy, and at 3, 6 and 12 months after surgery Each was evaluated. For the evaluation of IPSS, the patient's own self-filling method was used.
In addition, IPSS will give 0 points for no symptoms for the questions I to VII below.
Less than once every 5 times: 1 point b. Less than once every 2 times: 2 points c. Once every 2 times: 3 points d. More than once every 2 times: 4 points e. Almost always: 5 points The lower urinary tract symptoms are self-assessed with a total of 35 points.

I. Do you feel that urine still remains after urination?
II. After urinating, may you go to urination again (frequency of urination) within 2 hours?
III. Does urine break up during urination (discontinuity during urination)?
IV. Do you endure your urine and have leaked or rushed to the bathroom (urine control)?
V. How often do you feel that your urination momentum is weak (urine momentum)?
VI. Do you have any problems when you urinate? How often do you see it?
VII. How many times a night (number of urinations at night) do you get up to urinate (not when you wake up)
The urine flow rate was measured and evaluated with respect to the maximum urinary flow rate (ml / sec) and urine output (ml) using a urofluorometer (DANTEL ELEKTRONIK Ns, Etude ™ 9024 A0061, Denmark).

Example 1
I-125 permanent insertion brachytherapy was performed for the localized prostate cancer. Using transrectal ultrasound (Aroka SSD-1000, Tokyo) and treatment planning system (CMS Interplant ver3.3, Missouri, USA), the prescription dose for each case was 145 Gy in principle. Immediately after the treatment, oral administration of the aforementioned silodosin, tamsulosin hydrochloride, or naphthopidyl was started, and oral administration of each drug was continued until 12 months after the treatment.

The result of IPSS evaluation is shown in FIG.
In the IPSS evaluation before treatment (shown as “Pre” in FIG. 1, the same applies to the following figures), the total score of IPSS in each group of silodosin, tamsulosin hydrochloride, or naphthopidil is 8.0 ± 0.9, respectively. (Mean ± SE), 8.1 ± 0.7, 10.2 ± 1.1, and no difference was observed. The total scores of IPSS at 3 months after the treatment were 15.0 ± 1.4 (mean ± SE), 17.2 ± 0.9, and 21.4 ± 1.6 for the silodosin, tamsulosin hydrochloride, and naphthopidyl groups, respectively. Vs. naphthopidyl: P = 0.0028). Next, the total score of IPSS at 6 months after the treatment was 12.5 ± 1.6 (mean ± SE), 14.0 ± 0.9, 17.1 ± 1.5 for the silodosin, tamsulosin hydrochloride, and naphthopidyl groups, respectively. The improvement effect was excellent (silodosin vs. naphthopidyl: P = 0.0323). Furthermore, 12 months after the treatment, the total IPSS score was 6.0 ± 3.4 (mean ± SE), 9.5 ± 0.9, and 11.9 ± 1.9 for the silodosin, tamsulosin hydrochloride, and naphthopidyl groups, respectively. The improvement effect was excellent.

Next, in the study using the QOL score (see FIG. 2), the same score before treatment is 2.9 ± 0.2 (mean ± SE), 3.1 ± 0.1, and 3.4 ± 0.2 for the silodosin, tamsulosin hydrochloride, and naphthopidyl groups, respectively. , Did not recognize the difference. The scores after 3 months of treatment were 3.7 ± 0.2 (mean ± SE), 4.2 ± 0.2, and 4.6 ± 0.2 for the silodosin, tamsulosin hydrochloride, and naphthopidyl groups, respectively. QOL impairment due to urination problems in the silodosin group Was minimal (silodosin vs. naphthopidyl: P = 0.0018, silodosin vs. tamsulosin: P
= 0.0719). Furthermore, the same scores at 6 months after the treatment were 3.4 ± 0.3 (mean ± SE), 3.7 ± 0.2, and 4.2 ± 0.2 for the silodosin, tamsulosin hydrochloride, and naphthopidyl groups, respectively (silodosin vs. naphthopidyl: P = 0.0348, treatment 12). The same score after 2 months was 2.0 ± 1.0 (mean ± SE), 2.9 ± 0.2, and 3.3 ± 0.3 for the silodosin, tamsulosin hydrochloride, and naphthopidyl groups, respectively. The improvement in QOL of urination was remarkable.

In the uroflometry evaluation (see Fig. 3), the single urination volume (ml) before treatment was 273.4 ± 23.6 (mean ± SE), 247.8 ± 13.5, 237.3 ± 14.9 for the silodosin, tamsulosin hydrochloride and naphthopidyl groups, respectively. And no difference was found between the three groups. The amount of urination (ml) at 3 months after treatment was 200.3 ± 21.3 (mean ± SE), 169.0 ± 7.8, and 193.1 ± 12.5 for the silodosin, tamsulosin hydrochloride, and naphthopidyl groups, respectively. (Ml) were 209.4 ± 24.7 (mean ± SE), 171.7 ± 9.4, and 213.2 ± 14.6 for the silodosin, tamsulosin hydrochloride, and naphthopidyl groups, respectively, and the decrease in the amount of single urination in the silodosin group was slight. The urine output (ml) at 12 months after treatment was 301.8 ± 94.3 (mean ± SE), 181.8 ± 9.3, and 187.0 ± 17.1 for the silodosin, tamsulosin hydrochloride, and naphthopidyl groups, respectively. Recovery to baseline in the silodosin group However, the earliest tendency was recognized.

In the evaluation of urinary flow rate in uroflowmetry (see FIG. 4), the maximum urinary flow rate (ml / sec) before treatment is 15.8 ± 0.9 (mean ± SE), 15.9 ± 0.7, respectively for the silodosin, tamsulosin hydrochloride and naphthopidyl groups. It was 15.8 ± 0.9, and there was no difference between the 3 groups. The maximum urinary flow rate (ml / sec) at 3 months after treatment was 12.0 ± 0.9 (mean ± SE), 11.8 ± 0.5, and 11.6 ± 0.8 for the silodosin, tamsulosin hydrochloride, and naphthopidyl groups, respectively. No difference was observed. However, the maximum urinary flow rate (ml / sec) at 6 months after treatment was 14.4 ± 1.0 (mean ± SE), 13.2 ± 0.6, and 11.6 ± 0.8 for the silodosin, tamsulosin hydrochloride and naphthopidyl groups, respectively (silodosin vs. naphthopidyl: P = 0.0677), and the maximum urinary flow rate (ml / sec) at 12 months after treatment was 16.5 ± 1.9 (mean ± SE), 13.9 ± 0.5, 14.1 ± 1.2, respectively, in the silodosin, tamsulosin hydrochloride and naphthopidyl groups, the silodosin group The maximum urinary flow rate recovered rapidly at 6 months, and the improvement trend was remarkable thereafter.

As shown in the above results, in the examples in which the silodosin preparation was formulated according to the present invention, the peak value of IPSS was significantly reduced, and the QOL score was quickly recovered, compared with the conventional α ₁ receptor blocker. As a result, the return to the baseline is promptly promoted. Furthermore, also in objective evaluation in urofurometry, the disturbance of the maximum urine flow rate value is quickly recovered by prescribing the silodosin preparation, and the decrease in the amount of single urination due to radiation irritation symptoms is also recovered early.

  According to the present invention, lower urinary tract symptoms are greatly improved after brachytherapy. Therefore, it is useful as a prophylaxis and / or treatment of lower urinary tract symptoms after brachytherapy, and is also useful as a method for treating prostate cancer in combination with brachytherapy and this preparation.

The graph which shows the time-dependent change of the IPSS total score in each dosing group of silodosin, tamsulosin hydrochloride, and naphthopidyl (in the figure, the vertical line attached to each plot shows SE) The graph which shows the time-dependent change of the QOL score in each administration group of silodosin, tamsulosin hydrochloride, and naphthopidyl (in the figure, the vertical line attached to each plot shows SE) The graph which shows the time-dependent change of the amount of single urination (ml) in each dosing group of silodosin, tamsulosin hydrochloride, and naphthopidyl (in the figure, the vertical line attached to each plot shows SE) The graph which shows the time-dependent change of the maximum urine flow rate (ml / sec) in each dosing group of silodosin, tamsulosin hydrochloride, and naphthopidyl (in the figure, the vertical line attached to each plot shows SE).

Claims (8)

  A prophylactic and / or therapeutic agent for lower urinary tract symptoms after brachytherapy, comprising silodosin or a pharmacologically acceptable salt thereof or a solvate thereof as an active ingredient.   The therapeutic and / or prophylactic agent according to claim 1 in brachytherapy using I-125 as a radiation source.   To be used in combination with brachytherapy, which contains silodosin or a pharmacologically acceptable salt thereof or a solvate thereof in an effective amount for lower urinary tract symptoms after brachytherapy Silodosin formulation.   4. A silodosin formulation according to claim 3 for use in combination with brachytherapy using I-125 as a radiation source.   0.1-100 mg per day for adults or 0.01-100 mg per day for adults parenterally, or a pharmacologically acceptable salt thereof or a solvate thereof, for brachytherapy A method for administering a silodosin preparation, which is administered before and / or after.   After starting brachytherapy, silodosin or a pharmacologically acceptable salt thereof or a solvate thereof within a range of 0.1 to 50 mg per dose, 1 to 3 times a day for at least 3 months A method for administering a silodosin preparation, characterized by being orally administered over a period of time.   QOL improvement in the treatment of early prostate cancer characterized by administering a silodosin preparation containing silodosin or a pharmacologically acceptable salt thereof or a solvate thereof as an active ingredient after initiation of brachytherapy Method.   A method for treating early prostate cancer, comprising a combination of brachytherapy and administration of a silodosin preparation containing silodosin or a pharmacologically acceptable salt thereof or a solvate thereof as an active ingredient.

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