WO2024252511A1 - Cancer therapeutic agent and cancer treatment method - Google Patents

Abstract

[PROBLEM] To provide: a cancer therapeutic agent that is configured to, when administered into the abdominal cavity, increase the residence time in an abdominal cavity while also increasing the contact area with an affected part in the abdominal cavity; and a cancer treatment method. [SOLUTION] Provided is a cancer therapeutic agent to be administered into the abdominal cavity, the cancer therapeutic agent including a pharmaceutical agent comprising: a fixing material that has fluidity prior to administration and that decreases in fluidity in the abdominal cavity after administration and fixes to the inner surface of the abdominal cavity; and a cancer therapeutic substance.

Description

Cancer treatment agent and cancer treatment method

The present invention relates to a cancer treatment agent and a cancer treatment method using the agent.

Many advanced cancers, such as gastric cancer, that are considered incurable are complicated by peritoneal dissemination. When peritoneal dissemination occurs, it is extremely difficult to completely remove it through surgery, so treatment with anticancer drugs (chemotherapy) is carried out. However, in chemotherapy for peritoneal dissemination, even when anticancer drugs are administered systemically via intravenous administration, sufficient pharmacological effects are often not achieved, and there is a need to establish new treatment methods.

The following non-patent document 1 describes intraperitoneal chemotherapy, in which an anticancer drug such as paclitaxel is administered directly into the peritoneal cavity, as a new treatment method for peritoneal dissemination in order to solve the above-mentioned problems.

Ishigami H, Fujiwara Y, Fukushima R, et al. Phase III Trial Comparing Intraperitoneal and Intravenous Paclitaxel Plus S-1 Versus Cispl atin Plus S-1 in Patients With Gastric Cancer With Peritoneal Metastasis: PHOENIX-GC Trial. Journal of Clinical Oncology 2018 Jul 1; 36 (19): 1922-1929.

In intraperitoneal chemotherapy, the interval between intraperitoneal drug administrations is typically about once a week, depending on the type of anticancer drug used. However, the drug's effective concentration (drug concentration) only remains in the abdominal cavity for a short period of time (approximately 24 to 48 hours) and is quickly absorbed and eliminated by the peritoneum.

In addition, peritoneal dissemination often spreads throughout the abdominal cavity, so to obtain sufficient efficacy, the drug administered intraperitoneally must be spread evenly over the surface of the affected area to increase the contact area and duration of the drug with the affected area as much as possible. However, because the drug is liquid and the amount administered is limited, it is difficult to spread it widely over the entire inner surface of the abdominal cavity.

As described above, in intraperitoneal chemotherapy for peritoneal dissemination, it is important to deliver a high concentration of drugs that remain on the entire inner surface of the peritoneal cavity for a long period of time in order to achieve an effective antitumor effect. However, there are issues with the drug concentration and drug contact area, as mentioned above, and there is room for improvement.

At least one embodiment of the present invention has been made in consideration of the above circumstances, and specifically aims to provide a cancer treatment agent and a cancer treatment method that can increase the contact area with the affected area in the abdominal cavity when administered intraperitoneally, while prolonging the residence time of the drug in the abdominal cavity.

The above object of the present invention can be achieved by any one of the following (1) to (18).

(1) A cancer treatment agent to be administered into the abdominal cavity, the cancer treatment agent comprising: an anchoring material that has fluidity before administration and that, after administration, has its fluidity reduced within the abdominal cavity and is anchored to the inner surface of the abdominal cavity; and a drug that contains a cancer treatment substance.

(2) The cancer treatment agent according to (1) above, wherein the cancer treatment substance is a particulate drug dispersed in a biodegradable material.

(3) The cancer treatment agent according to (1) or (2) above, wherein the fixing material is a temperature-responsive material that is liquid at temperatures other than near body temperature and changes into a sol or gel at near body temperature, or that is a sol at temperatures other than near body temperature and changes into a gel at near body temperature.

(4) The cancer treatment agent according to (3) above, wherein the temperature-responsive material changes into a sol or gel in 5 to 15 minutes at or near body temperature.

(5) The cancer treatment agent according to (3) or (4) above, wherein the temperature-responsive material includes at least one of N-substituted (meth)acrylamide derivatives, poly(N-acryloylpyrrolidine), nitrogen-containing cyclic polymers, vinyl-containing amino acids or esters thereof, poly(vinyl methyl ether), poly(ethylene glycol)/poly(propylene glycol), and polylactic acid-polyglycolic acid-polyethylene oxide copolymers.

(6) Any of the cancer treatment agents (1) to (5) above, wherein the drug is decomposed in the abdominal cavity within a period of 1 to 2 weeks.

(7) Any of the cancer treatment agents (1) to (6) above, wherein the average particle size of the agent is 10 μm or more and 100 μm or less.

(8) A cancer treatment agent according to any one of (1) to (7) above, wherein the biodegradable material includes at least one of lipids, fatty acids, waxes, and derivatives thereof.

(9) A cancer treatment method comprising: an administration step of administering a cancer treatment agent containing at least a fixing material that has fluidity before administration and that, after administration, becomes fixed to the inner surface of the abdominal cavity by reducing its fluidity in the abdominal cavity, and a drug that contains at least a cancer treatment substance, into the abdominal cavity of a patient through an administration tube that is placed in the abdominal cavity of the patient and communicates with the outside; and a position change step of changing the position of the patient to fix the cancer treatment agent in the abdominal cavity.

(10) A cancer treatment method according to (9) above, in which the patient's position is changed to at least a supine position, a left lateral position, and a right lateral position.

(11) The cancer treatment method according to (9) or (10), wherein the patient's position is further changed to at least one of the following positions: prone position, buttocks-fisted supine position in which the patient's occiput is lower than the buttocks, and head-fisted supine position in which the patient's occiput is higher than the buttocks.

(12) A cancer treatment method according to any one of (9) to (11) above, in which the table for changing the patient's position has a storage section for storing at least a portion of the tube inserted into the abdominal cavity of the patient that is exposed to the outside of the body.

(13) A cancer treatment method according to any one of (9) to (12) above, in which the cancer treatment agent is administered into the abdominal cavity while the patient's position is being changed.

(14) Any of the cancer treatment methods (9) to (13) above, in which the patient position changing procedure is performed for a total of 60 minutes or more per treatment.

(15) A cancer treatment method according to any one of (9) to (14) above, in which the drug is a particle in which at least the cancer treatment substance is dispersed in a biodegradable material.

(16) Any of the cancer treatment methods (9) to (15) above, wherein the fixing material is a temperature-responsive material that is liquid at a temperature other than near the patient's body temperature and changes into a sol or gel at near the patient's body temperature, or that is a sol at a temperature other than near the patient's body temperature and changes into a gel at near the patient's body temperature.

(17) A method for treating cancer, comprising: a first administration step of administering a fixable material that is to be fixed to the inner surface of the abdominal cavity of a patient through an administration tube that communicates with the outside; a second administration step of administering a drug that contains at least a cancer treatment substance through the administration tube into the abdominal cavity of the patient; and a position change step of changing the position of the patient in order to apply at least one of the fixable material administered by the first administration step and the drug administered by the second administration step to the abdominal cavity of the patient.

(18) A method for treating cancer, comprising: a first administration step of administering a fixative material that is to be fixed to the inner surface of the abdominal cavity of a patient through an administration tube that communicates with the outside; a position change step of changing the position of the patient in order to apply the fixative material administered in the first administration step to the abdominal cavity of the patient; and a second administration step of administering a drug containing at least a cancer treatment substance into the abdominal cavity of the patient through the administration tube after administering the fixative material in the first administration step.

(19) The cancer treatment method according to (17) or (18), wherein the fixing material includes a sol and/or a gel.

According to the present invention, when administered into the peritoneal cavity, particulate drugs (microspheres) made of at least a cancer treatment substance dispersed in a biodegradable material can be maintained in the peritoneum by the fixing material, which has fluidity before administration and decreases in fluidity after administration and fixes to the inner surface of the peritoneal cavity. Therefore, after administration into the peritoneal cavity, the drug can be released gradually while being in contact with the entire peritoneum. As a result, the efficacy of the drug after administration can be maintained for a long period of time, such as one to two weeks, and sufficient therapeutic effects against peritoneal dissemination can be expected.

1 is a flowchart showing the steps of a cancer treatment method according to the present embodiment. FIG. 2 is a diagram showing the state in which an administration tube used in the cancer treatment method according to the present embodiment is attached. 1A to 1C are diagrams showing postures taken in a posture changing procedure. 1A to 1C are diagrams showing postures taken in a posture changing procedure. FIG. 2 is a diagram showing a state during treatment in the cancer treatment method according to the present embodiment. FIG. 2 is a diagram showing the periphery of a storage section of a bed used in the cancer treatment method according to the present embodiment. 1A to 1C are diagrams showing examples of the form of a protective member used in the cancer treatment method according to the present embodiment. 11A to 11C are diagrams showing other examples of the protective member used in the cancer treatment method according to the present embodiment. 13 is a flowchart showing a modified example of the cancer treatment method according to the present embodiment.

Below, the form for carrying out the present invention will be described in detail with reference to the drawings. The embodiment shown here is an example to embody the technical idea of the present invention, and does not limit the present invention. Furthermore, all other possible forms, examples, and operational techniques that can be conceived by those skilled in the art without departing from the gist of the present invention are included in the scope and gist of the present invention, and are included in the scope of the inventions described in the claims and their equivalents.

Furthermore, for the convenience of illustration and ease of understanding, the drawings attached to this specification may be represented diagrammatically with appropriate conversions from the actual objects in terms of scale, aspect ratio, shape, etc., but these are merely examples and do not limit the interpretation of the present invention.

In the following explanation, when ordinal numbers such as "first" and "second" are used, they are used for convenience and do not dictate any particular order, unless otherwise specified.

[Cancer treatments]
The cancer therapeutic agent according to this embodiment will be described.

The cancer treatment agent is administered into the abdominal cavity A1, and includes an anchoring material that has fluidity before administration, and which, over a predetermined period of time after administration, loses fluidity within the abdominal cavity A1 and anchors to the inner surface of the abdominal cavity A1 (the peritoneum A4 and surrounding organs, etc.), and a drug that includes a cancer treatment substance. The cancer treatment substance includes a particulate drug dispersed in a biodegradable material.

The cancer treatment agent can effectively treat and/or prevent peritoneal dissemination associated with cancer occurring in organs present in the abdominal cavity A1, such as stomach cancer, colon cancer, liver cancer, gallbladder cancer, pancreatic cancer, kidney cancer, etc.

<Fixing material>
The fixing material has fluidity when administered into the abdominal cavity A1, and after a predetermined time has passed, the fluidity decreases and the material becomes able to fix to the inner surface of the abdominal cavity A1. Here, "fluidity decreases" means that the material is in a state where it can fix to the inner surface of the abdominal cavity A1, and includes a state where the material changes to a solid state or a liquid state that has a high viscosity and can adhere to the abdominal cavity A1.

The fixing material can suitably be a temperature-responsive material that is liquid at temperatures other than near body temperature (e.g., 35.0°C or higher and 40°C or lower) and changes into a sol or gel at near body temperature, or that is a sol at temperatures other than near body temperature and changes into a gel at near body temperature. By using a temperature-responsive material as the fixing material, when the cancer treatment agent is administered into the abdominal cavity A1, the fluidity of the agent gradually decreases as the drug temperature approaches near body temperature, where the fluidity properties may change, and the agent can be fixed to the inner surface of the abdominal cavity A1 when the temperature reaches near body temperature.

The temperature-responsive material preferably changes into a sol or gel in 5 to 15 minutes at about body temperature. This time is the time required for the cancer treatment agent administered into abdominal cavity A1 in a fluid state to be distributed throughout abdominal cavity A1 while changing the position of patient P in the cancer treatment method described below. The cancer treatment agent containing the temperature-responsive material is applied to the inner surface of abdominal cavity A1 by changing the position of patient P within the aforementioned time period in which the fluidity of the agent decreases after administration into abdominal cavity A1, and the fluidity of the agent decreases and the agent becomes established after a predetermined time has passed.

The temperature-responsive material can be configured to contain at least one of N-substituted (meth)acrylamide derivatives, poly(N-acryloylpyrrolidine), nitrogen-containing cyclic polymers, vinyl-containing amino acids or esters thereof, poly(vinyl methyl ether), poly(ethylene glycol)/poly(propylene glycol), polylactic acid-polyglycolic acid-polyethylene oxide copolymer. The temperature-responsive material may be any material that has fluidity at least before administration and whose fluidity decreases at temperatures near body temperature after administration into the abdominal cavity A1. For example, the materials disclosed in JP 2000-080158, JP 2005-239860, etc. can be suitably used.

In addition to temperature-responsive gels, the fixing material may be a gel that changes in fluidity to factors other than heat, such as a stimuli-responsive gel (stimuli such as pH changes) or a molecular stimuli-responsive gel (gel that swells and shrinks in response to recognizing specific molecules).

<Medicine>
The drug is composed of at least a cancer treatment substance. The drug can be in the form of particles containing at least a biodegradable material. The drug can be in the form of sustained-release microspheres formed by spray drying or other manufacturing methods using a mixture of a biodegradable material, a drug (cancer treatment substance), and additives, solvents, etc., appropriately adjusted. By forming the drug into microspheres, the initial release amount of the cancer treatment substance and the release rate during the subsequent release period can be appropriately controlled, allowing the substance to be released continuously in vivo for a certain period of time.

Cancer therapeutic substances refer to substances such as anticancer drugs that have a cytocidal effect, such as the destruction or death of cancer cells. The cancer therapeutic substance may be any anticancer drug that is generally used in cancer treatment. Examples of cancer therapeutic substances include paclitaxel (active ingredient: paclitaxel), actinomycin (active ingredient: actinomycin D), amrubicin (active ingredient: amrubicin hydrochloride), ifosfamide (active ingredient: ifosfamide), irinotecan (active ingredient: irinotecan hydrochloride hydrate), etoposide (active ingredient: etoposide), epirubicin (active ingredient: epirubicin hydrochloride), oxaliplatin (active ingredient: oxaliplatin), opiate (active ingredient: opiate hydrochloride), and rifampicin (active ingredient: rifampicin hydrochloride). nivolumab (recombinant gene)), cabazitaxel (active ingredient: cabazitaxel acetone adduct), carboplatin (active ingredient: carboplatin), gemcitabine (active ingredient: gemcitabine hydrochloride), Cyramza (active ingredient: ramucirumab (recombinant gene)), Gemzar (active ingredient: gemcitabine hydrochloride), cyclophosphamide (active ingredient: cyclophosphamide hydrate), cisplatin (active ingredient: cisplatin), cytarabi (active ingredient: cytarabine), cetuximab (active ingredient: cetuximab (genetical recombination)), dacarbazine (active ingredient: dacarbazine), dasatinib (active ingredient: dasatinib), doxorubicin (active ingredient: doxorubicin hydrochloride), docetaxel (active ingredient: docetaxel), trastuzumab (active ingredient: trastuzumab (genetical recombination)), trastuzumab emtansine (active ingredient: trastuzumab emtansine (genetical recombination)), nifedipine Suitable examples of the cancer treatment substance include nimustine (active ingredient: nimustine hydrochloride), nedaplatin (active ingredient: nedaplatin), nogitecan (active ingredient: nogitecan hydrochloride), perjeta (active ingredient: pertuzumab (genetically recombined)), panitumumab (active ingredient: panitumumab (genetically recombined)), vinorelbine (active ingredient: vinorelbine tartrate), vincristine (active ingredient: vincristine sulfate), and fluorouracil (active ingredient: fluorouracil). One type of cancer treatment substance may be used, or two or more types may be used in combination. The dose of the cancer treatment substance varies depending on the type of cancer to be treated and the type of cancer to be treated, and can be determined by appropriately selecting a dose generally used for treatment.

The biodegradable material used in the drug has biodegradability and has the property of being dispersible in the cancer treatment substance. The biodegradable material preferably contains at least one of lipids, fatty acids, waxes, and derivatives thereof. Suitable examples of the biodegradable material include polyesters such as polylactide (PLA), polyglycolide (PGA), and their copolymers, such as polylactide-co-glycolide (PLGA). In addition, the biodegradable material may be any material that has biodegradability that does not inhibit the sustained release or efficacy of the cancer treatment substance or has very little risk of inhibition, and suitable examples include the materials disclosed in JP 2005-35994, etc.

From the viewpoint of sustained release, the average particle size of the drug is preferably 10 μm or more and 100 μm or less. This numerical range of average particle size is the size required to obtain sufficient drug concentration and appropriate sustained release when the efficacy of the cancer treatment drug administered into the abdominal cavity A1 is extended for about 1 to 2 weeks. The average particle size of the drug can be adjusted depending on the properties of the biodegradable material used.

In addition, drugs with different average particle sizes can be mixed together to adjust the sustained release period. In this case, the drugs may be of the same type, or different types of drugs may be used in combination.

As described above, when the cancer treatment agent according to this embodiment is administered into the abdominal cavity A1, it has fluidity before administration, but after administration, the fluidity decreases in the abdominal cavity A1, and due to the action of the fixing material that fixes to the inner surface of the abdominal cavity A1, the particulate drug (microspheres) in which at least a cancer treatment substance is dispersed in a biodegradable material can be maintained in the peritoneum. Therefore, after administration into the abdominal cavity A1, the cancer treatment agent can release the drug at a concentration that provides medicinal efficacy over a long period of time, with the drug in contact with the entire abdominal cavity A1 evenly. Therefore, the cancer treatment agent can maintain its medicinal efficacy for a long period of time, about one to two weeks, after administration.

The cancer treatment agent only needs to be maintained in contact with the surface of the peritoneum A4 within the abdominal cavity A1 by the action of the fixing material. For this reason, the cancer treatment agent is in the form of at least a mixture of the fixing material and the drug, but as in a modified example of the cancer treatment method described below, the fixing material may be administered first, and then the drug may be administered before the fixing material settles within the abdominal cavity A1. In other words, the fixing material and the drug may be mixed immediately before the administration procedure described below.

[Cancer treatment methods]
Next, a cancer treatment method using the above-mentioned cancer therapeutic agent will be described.

As shown in FIG. 1, the cancer treatment method includes an arrangement step S1 of arranging an administration tube 10 communicating with the outside in the abdominal cavity A1 of a patient P, an administration step S2 of administering a cancer treatment agent containing at least an anticancer agent and a fixing material that has fluidity before administration and that reduces in fluidity in the abdominal cavity A1 after administration and fixes to the inner surface of the abdominal cavity A1 (peritoneum A4 and surrounding organs, etc.) and an anticancer agent into the abdominal cavity A1 of the patient P via the administration tube 10, and a position change step S3 of changing the position of the patient P to fix the cancer treatment agent in the abdominal cavity A1. The cancer treatment method according to this embodiment is not limited to the flowchart shown in FIG. 1, and other steps can be performed before or after each step as necessary.

Placement Procedure
The placement procedure S1 is an operation of placing the administration tube 10 in the abdominal cavity A1 of the patient P. The placement procedure S1 does not necessarily have to be performed immediately before the administration procedure S2, and can be performed before the cancer treatment method is performed.

As shown in FIG. 2, the administration tube 10 comprises a tube body 11, an internal fixation part 12, an external fixation part 13, a connection part 14, and a lid part 15. The administration tube 10 is attached with a part of it being placed in the abdominal cavity A1 of the patient P, and is used when administering a cancer treatment agent into the abdominal cavity A1. The administration tube 10 is fixed with the internal fixation part 12 and the external fixation part 13 clamping the biological tissue between the skin A2 and the peritoneum A4.

The tube body 11 is a flexible hollow member with an inner cavity formed from the tip to the base end. The tip of the tube body 11 is placed in the abdominal cavity A1, and the base end is placed outside the living body.

The internal fixation part 12 is disposed at the tip side of the tube body 11 and is used to fix the administration tube 10 to the living body. The internal fixation part 12 can be composed of, for example, a balloon having an internal space (lumen) into which a pressurized medium (e.g., a fluid such as saline or air) used for expansion flows, or a hollow disk-shaped bumper formed integrally with the outer circumferential surface of the tube body 11. Figure 2 shows the internal fixation part 12 formed from a balloon.

The internal fixation part 12 is not particularly limited as long as it has a form that allows the tip of the tube body 11 to be retained and fixed within the abdominal cavity A1. The internal fixation part 12 may be a balloon type or bumper type, or may be a self-expanding stent that expands after being retained within the body to retain the tube body 11, or a combination of these forms may be used. The internal fixation part 12 may also be provided with an additional cuff (not shown) on the tube body 11 to prevent it from coming off. By providing a cuff, the administration tube 10 can be more effectively prevented from unintentionally coming off.

The external fixation part 13 is in the form of a small piece extending in a direction intersecting the axial direction of the tube body 11 inserted into the perforation hole A3. The external fixation part 13 is positioned in contact with the outer surface of the epidermis of the skin A2. The external fixation part 13 prevents the administration tube 10 from being buried in the perforation hole A3 and from being displaced.

The connection part 14 is composed of a connector arranged in communication with the base end of the tube body 11. The connection part 14 is detachably connected to an external connector 101 provided in communication with the base end of the external tube 100 of the infusion bag 200 filled with a cancer treatment agent. When the connection part 14 and the external connector 101 are connected, the opening of the connection part 14 and the opening of the external connector 101 are in communication with each other, so that the cancer treatment agent in the infusion bag 200 can flow into the abdominal cavity A1 of the patient P. There are no restrictions on the shape of the connection part 14 as long as it is at least detachable from the external connector 101 and has a locking function to maintain the connection state.

The lid 15 is attached to the external fixation part 13 via a hinge, and is attached so as to cover the opening of the connection part 14 when the connection to the external tube 100 is released after administration of the cancer treatment drug. This ensures that the tube body 11 of the administration tube 10 is airtight with the opening of the connection part 14 closed, preventing the entry of foreign matter from the outside and reducing the risk of infection.

As described above, the administration tube 10 can be detachably connected to the external tube 100 via the connection part 14, and the connection state between the connection part 14 and the external connector 101 is maintained unless it is intentionally released. Therefore, the administration tube 10 does not have to worry about the needle being unintentionally removed when changing body position, which can occur with the puncture method. The administration tube 10 can also be placed in the skin as a subcutaneously embedded intradermal port, not limited to the fixation method using the internal fixation part 12 and the external fixation part 13. The administration tube 10 may also include a needle in addition to the tube body 11.

Administration Procedure
Administration procedure S2 is an operation for administering a cancer therapeutic agent by connecting the external connector 101 of the external tube 100 to the connection part 14 of the administration tube 10 placed in the patient P. As described above, the cancer therapeutic agent administered in administration procedure S2 contains an anchoring material whose fluidity decreases near body temperature and a drug having a cancer therapeutic substance, and therefore, when a predetermined time has passed after administration, the cancer therapeutic agent anchors to the surface of the peritoneum A4 in the abdominal cavity A1.

The administration timing in administration procedure S2 can be before the start of position change procedure S3 or in accordance with the start timing of position change procedure S3. That is, administration procedure S2 can be performed immediately before performing position change procedure S3 or during position change procedure S3 (while changing position). In addition, the dose of the cancer therapeutic agent in administration procedure S2 is not particularly limited and can be set appropriately. The dose of the cancer therapeutic agent can be set, for example, based on the number of position changes in position change procedure S3, and after the start of position change procedure S3, the same amount can be administered in the same number of portions as the number of position changes, or the agent can be administered continuously from the start to the end of position change procedure S3. For example, if the position is changed three times in position change procedure S3, 1/3 of the total dose can be administered each time the position is changed.

<Position change procedure>
The position changing procedure S3 is an operation for changing the position of the patient P so that the cancer therapeutic agent administered in the administration procedure S2 is distributed evenly throughout the abdominal cavity A1. The position changing procedure S3 adheres the cancer therapeutic agent administered into the abdominal cavity A1 to the inner surface of the abdominal cavity A1, and fixes the cancer therapeutic agent to the inner surface of the abdominal cavity A1 as the temperature of the fixing material becomes close to body temperature over a predetermined time.

Figures 3 and 4 show the positions that are changed in position change step S3.

The position change procedure S3 includes operations for changing the basic positions of supine, left lateral, and right lateral as shown in FIG. 3. The supine position is the position (posture) in which patient P lies on the bed 300. The supine position is the position in which patient P lies on his/her back on the bed 300 as shown in FIG. 3(a). The right lateral position is the position in which patient P lies on the bed 300 with his/her right arm underneath as shown in FIG. 3(b). The left lateral position is the position in which patient P lies on the bed 300 with his/her left arm underneath as shown in FIG. 3(c).

In addition to the supine, left and right lateral positions shown in FIG. 3, the position change procedure S3 may also change the position shown in FIG. 4. Specifically, the position change procedure S3 includes the actions of changing the position to the prone position, buttocks fisted position and head fisted position as shown in FIG. 4. The prone position is a position in which the patient P lies face down on the bed 300 as shown in FIG. 4(a). The buttocks fisted position is a position in which the patient P lies supine on the bed 300 with the back of the patient P's head lower than the buttocks as shown in FIG. 4(b). The head fisted position is a position in which the patient P lies supine on the bed 300 with the back of the patient P's head higher than the buttocks as shown in FIG. 4(c). The buttocks-fisted supine position and head-fisted supine position may be performed with patient P lying face down on the bed 300.

The position change procedure S3 can set a position retention time for maintaining the position according to the settling time of the fixing material of the administered cancer treatment agent (the time from the start of administration to when fluidity is at its lowest after administration). For example, if the settling time of the fixing material contained in the cancer treatment agent is 15 minutes, the position retention time can be set to 15 minutes. By setting the position retention time in this way, the cancer treatment agent that has adhered to the abdominal cavity A1 can be set when the position is maintained.

The timing of the position change procedure S3 can be set appropriately according to the settling time of the fixing material of the administered cancer treatment agent (the time from the start of administration until the fluidity becomes the lowest after administration).

In the flowchart shown in FIG. 1, the administration procedure S2 and the position change procedure S3 are performed once each, but the administration procedure S2 and the position change procedure S3 can be repeated a predetermined number of times alternately in one treatment. One treatment is a cancer treatment including the administration procedure S2 and the position change procedure S3, which are performed when the patient P visits a medical institution. For example, if the administration procedure S2 and the position change procedure S3 are performed four times each, and the position change procedure is performed for a total of 60 minutes or more in one treatment, first, a predetermined amount of the cancer treatment agent is administered (e.g., 1/4 of the total daily dose) by the first administration procedure S2 → the patient is maintained in a supine position for 15 minutes by the first position change procedure S3 → the patient is maintained in a supine position for 15 minutes by the second administration procedure S2 → the patient is maintained in a supine position for 15 minutes by the second position change procedure S3. Change from supine position to left lateral position and hold for 15 minutes → administer a predetermined amount of cancer treatment agent (e.g., 1/4 of the total daily dose) by the third administration procedure S2 → change from left lateral position to right lateral position by the third position change procedure S3 and hold for 15 minutes → administer a predetermined amount of cancer treatment agent (e.g., 1/4 of the total daily dose) by the fourth administration procedure S2 → change from right lateral position to prone position by the fourth position change procedure S3 and hold for 15 minutes. In this way, by repeating the administration procedure S2 and the position change procedure S3 multiple times, the cancer treatment agent can be more effectively distributed to the inner surface of the abdominal cavity A1.

The bed 300 used in the cancer treatment method is provided with a storage section 310, as shown in Figures 5A and 5B.

The storage section 310 has a form capable of storing the members exposed to the outside of the patient P's body (such as the connection section 14) and the external tube 100, and can be formed, for example, as shown in FIG. 5B, as a recess formed in the bed 300. The storage section 310 can store the members exposed to the outside of the patient P's body (such as the connection section 14) and the external tube 100 when the patient P changes his/her position to a position (such as prone position) in which the abdomen where the administration tube 10 is installed may come into contact with the surface of the bed 300. This prevents the connection section 14, the external tube 100, etc. from coming into direct contact with the abdomen during the position change procedure, and prevents incomplete administration of the cancer treatment drug due to crushing of the external tube 100 and damage to the external tube 100.

In addition, as a countermeasure against the crushing of the external tube 100 during the position change procedure S3, it is effective to attach a protective member 110 that covers the outer circumferential surface of the external tube 100 as shown in FIG. 6A. The protective member 110 is attached so as to cover the outer circumferential surface of the external tube 100, and suppresses or prevents deformation of the external tube 100.

The protective member 110 can be configured as a protective cover 110A, which is a cylindrical member made of an elastic member as shown in FIG. 6A and has a slit in its inner cavity through which the external tube 100 can be inserted and removed, or a protective coil 110B, which is wound helically around the outer circumferential surface of the external tube 100 as shown in FIG. 6B. The form of the protective member 110 is not limited to the protective cover 110A or the protective coil 110B, but may be any form that can prevent the external tube 100 from being crushed or damaged.

In the position change procedure S3, since the patient P may assume a position in which the abdomen of the patient P faces the bed 300, such as prone position, it is effective to use the storage section 310 and protective member 110 provided in the bed 300 to prevent incomplete administration of the cancer treatment agent due to the external tube 100 being crushed, etc.

Next, we will explain a modified example of the cancer treatment method according to this embodiment.

The modified cancer treatment method differs in the administration content of administration procedure S2 between placement procedure S1 and position change procedure S3 shown in Figure 1. As shown in Figure 7, the modified cancer treatment method includes placement procedure S11, a first administration procedure S12 for administering a fixing material, position change procedure S13, and a second administration procedure S14 for administering a drug containing at least an anticancer drug. Placement procedure S11 is similar to placement procedure S1 shown in Figure 1 described above, so a description thereof will be omitted.

In the modified cancer treatment method, the fixative material and drug contained in the cancer treatment agent are administered separately, as in the cancer treatment method described above.

First Administration Procedure
The first administration procedure S12 is an operation of administering the fixing material into the abdominal cavity A1 from the administration tube 10 placed in the placement procedure S11. The fixing material administered in the first administration procedure S12 has fluidity at the time of administration, and therefore can easily adhere to the peritoneum A4, which is the inner surface of the abdominal cavity A1, and the surfaces of the surrounding organs.

<Position change procedure>
The position change procedure S13 is an operation for changing the position of the patient P to spread the fixing material administered into the abdominal cavity A1 in the first administration procedure S12 to the inner surface of the abdominal cavity A1. By performing the position change procedure S13 after the first administration procedure S12, the fixing material is spread throughout the entire abdominal cavity A1. The first administration procedure S12 and the position change procedure S13 can be repeated multiple times while changing the position to be changed, thereby efficiently spreading the fixing material throughout the entire abdominal cavity A1.

Second Administration Procedure
The second administration procedure S14 is an operation of administering a drug from the administration tube 10 into the abdominal cavity A1. The second administration procedure S14 is performed after the first administration procedure S12 is performed to administer the fixing material and the fixing material is fixed. The drug administered in the second administration procedure S14 mixes with the fixing material in the abdominal cavity A1, and after a predetermined time has passed, the fixing material is fixed to the inner surface of the abdominal cavity A1 due to a decrease in the fluidity of the fixing material. Note that the second administration procedure S14 may be performed after the first administration procedure S12 is performed to administer the fixing material and before the fixing material is fixed (before the fixing material is fixed to the inner surface of the abdominal cavity A1 due to a decrease in the fluidity of the fixing material).

In the modified cancer treatment method, the patient P's position is changed to distribute the fixing material over the inner surface of the abdominal cavity A1, and then the drug is administered in the second administration procedure S14. This allows the drug to mix with the previously administered fixing material and remain in the peritoneum A4, which is the inner surface of the abdominal cavity A1, and the surrounding organs. If the second administration procedure S14 is performed after the fixing material is administered by performing the first administration procedure S12 and the fixing material has been fixed, the fixed fixing material acts as a semipermeable membrane and the drug diffuses through the fixed fixing material, so that the drug can remain in the peritoneum A4, which is the inner surface of the abdominal cavity A1, and the surrounding organs. On the other hand, if the second administration procedure S14 is performed after the fixing material is administered by performing the first administration procedure S12 and before the fixing material is fixed (before the fixing material is fixed to the inner surface of the abdominal cavity A1 due to a decrease in the fluidity of the fixing material), the temperature of the fixing material becomes close to body temperature, and the fixing material containing the drug is fixed to the inner surface of the abdominal cavity A1 due to a decrease in the fluidity of the fixing material. As the fluidity of the fixing material containing the drug decreases, the drug is fixed to the inner surface of the abdominal cavity A1, and the drug can be retained in the peritoneum A4, which is the inner surface of the abdominal cavity A1, and in the surrounding organs. The drug has a lower viscosity than the fixing material and is easily absorbed by the peritoneum A4, but by administering the drug with the fixing material applied to the abdominal cavity A1 in advance, the fixing material can be used to retain the drug for a long time. In addition, there is a lower risk of the tube coming loose than if the patient's position was changed while the drug is being administered, and the risk of exposure to the drug can also be reduced. Furthermore, there is no need to use microspheres or the like as the drug solution, and it is possible to use a drug made by mixing existing saline with an anticancer drug, expanding the range of drugs that can be used.

The modified cancer treatment method is not limited to the procedure shown in FIG. 7, and the order of the position change procedure S13 and the second administration procedure S14 can be reversed, and the order can be first administration procedure S12 → second administration procedure S14 → position change procedure S13, or the second administration procedure S14 can be performed before the first administration procedure S12. In either case, the drug and the fixing material can be mixed inside the abdominal cavity A1 during the position change in the position change procedure S13 and attached to the inner surface of the abdominal cavity A1. Furthermore, the first administration procedure S12, position change procedure S13, and second administration procedure S14 can be repeated as necessary. That is, the modified cancer treatment method may include a first administration procedure S12 in which a fixing material that is fixed to the inner surface of the abdominal cavity A1 of the patient P is administered into the abdominal cavity A1 of the patient P through an administration tube 10 that communicates with the outside in the abdominal cavity A1 of the patient P, a second administration procedure S14 in which a drug containing at least a cancer treatment substance is administered into the abdominal cavity A1 of the patient P through the administration tube 10, and a position change procedure S13 in which the position of the patient P is changed in order to apply at least one of the fixing material administered by the first administration procedure S12 and the drug administered by the second administration procedure S14 to the abdominal cavity A1 of the patient P.

As described above, the cancer treatment agent according to this embodiment is a cancer treatment agent administered into the abdominal cavity A1, and includes an anchoring material that has fluidity before administration, and whose fluidity decreases after administration in the abdominal cavity A1, so that the agent anchors to the inner surface of the abdominal cavity A1, and a drug that contains a cancer treatment substance.

The cancer treatment method according to this embodiment also includes an administration step S2 of administering a cancer treatment agent containing at least a fixing material that has fluidity before administration and that, after administration, becomes less fluid within the abdominal cavity A1 and fixes to the inner surface of the abdominal cavity A1, and a drug that contains at least a cancer treatment substance, into the abdominal cavity A1 of the patient P through an administration tube 10 that is placed within the abdominal cavity A1 of the patient P and communicates with the outside, and a position change step S3 of changing the position of the patient P to fix the cancer treatment agent in the abdominal cavity A1.

With this configuration, the cancer treatment agent can be administered into the abdominal cavity A1 and remain on the peritoneum A4, which is the inner surface of the abdominal cavity A1, and the surrounding organs while the patient is changed to a specified position, so that the drug can be released continuously for a longer period of time than with conventional treatment methods while being in contact with the entire surface of the peritoneum A4. Therefore, according to the cancer treatment agent of this embodiment and the cancer treatment method using this treatment agent, the efficacy of the cancer treatment agent after administration is maintained for a long period of time, about one to two weeks, and a sufficient treatment effect can be obtained against peritoneal dissemination.

10 administration tube,
11 Tube body,
12 Internal fixation part,
13 external fixation part,
14 Connection portion,
15 Lid portion,
100 outer tube,
101 external connector,
110 Protective member,
110A protective cover,
110B protection coil,
200 infusion bags,
300 beds,
310 Storage section A1 Abdominal cavity,
A2 Skin,
A3 Perforation hole,
A4 peritoneal P patient.

Claims (18)

A cancer therapeutic agent administered intraperitoneally,
A fixing material that has fluidity before administration and that has a decrease in fluidity in the abdominal cavity after administration and is fixed to the inner surface of the abdominal cavity;
A cancer therapeutic agent comprising: a drug containing a cancer therapeutic substance. The cancer treatment agent according to claim 1, wherein the cancer treatment substance is a particulate drug dispersed in a biodegradable material. The cancer treatment agent according to claim 1, wherein the fixing material is a temperature-responsive material that is liquid at temperatures other than near body temperature and changes into a sol or gel at near body temperature, or that is a sol at temperatures other than near body temperature and changes into a gel at near body temperature. The cancer treatment agent according to claim 3, wherein the temperature-responsive material changes into a sol or gel in 5 to 15 minutes at or near body temperature. The cancer treatment agent according to claim 2, wherein the temperature-responsive material includes at least one of N-substituted (meth)acrylamide derivatives, poly(N-acryloylpyrrolidine), nitrogen-containing cyclic polymers, vinyl-containing amino acids or esters thereof, poly(vinyl methyl ether), poly(ethylene glycol)/poly(propylene glycol), and polylactic acid-polyglycolic acid-polyethylene oxide copolymers. The cancer treatment agent according to claim 1, wherein the drug is decomposed in the abdominal cavity within a period of 1 to 2 weeks. The cancer treatment agent according to claim 1, wherein the average particle size of the drug is 10 μm or more and 100 μm or less. The cancer treatment agent according to claim 1, wherein the biodegradable material includes at least one of lipids, fatty acids, waxes, and derivatives thereof. 1. A method for treating cancer, comprising:
an administration step of administering a cancer therapeutic agent, the cancer therapeutic agent including at least a fixing material that has fluidity before administration and that, after administration, is reduced in fluidity in the abdominal cavity and fixed to the inner surface of the abdominal cavity, and a drug including at least a cancer therapeutic substance, into the abdominal cavity of the patient through an administration tube that is placed in the abdominal cavity of the patient and communicates with the outside;
and a position changing step of changing the position of the patient to allow the cancer therapeutic agent to settle in the abdominal cavity. The cancer treatment method according to claim 9, wherein the patient's position is changed to at least a supine position, a left lateral position, and a right lateral position. The cancer treatment method according to claim 10, wherein the patient's body position is further changed to at least one of the following body positions: prone position, buttocks-fisted supine position in which the patient's occiput is lower than the buttocks, and head-fisted supine position in which the patient's occiput is higher than the buttocks. The cancer treatment method according to claim 9, wherein the table for changing the patient's position has a storage section for storing at least a portion of the tube inserted into the abdominal cavity of the patient that is exposed to the outside of the body. The cancer treatment method according to claim 9, wherein the cancer treatment agent is administered into the abdominal cavity while the patient's body position is being changed. The cancer treatment method according to claim 9, wherein the patient position changing procedure is performed for a total of 60 minutes or more per treatment. The cancer treatment method according to claim 9, wherein the drug is a particle in which at least the cancer treatment substance is dispersed in a biodegradable material. The cancer treatment method according to claim 9, wherein the fixing material is a temperature-responsive material that is liquid at a temperature other than near the patient's body temperature and changes into a sol or gel at near the body temperature, or that is a sol at a temperature other than near the body temperature and changes into a gel at near the body temperature. 1. A method for treating cancer, comprising:
a first administration step of administering a fixing material to be fixed to an inner surface of the abdominal cavity of the patient through an administration tube communicating with the outside of the abdominal cavity of the patient into the abdominal cavity of the patient;
a second administration step of administering a drug containing at least a cancer therapeutic substance into the abdominal cavity of the patient through the administration tube;
A cancer treatment method comprising: a position changing step of changing the position of the patient to apply at least one of the fixing material administered by the first administration step and the drug administered by the second administration step into the abdominal cavity of the patient. The cancer treatment method according to claim 17, wherein the fixing material includes a sol and/or a gel.