Cancer therapeutic agent and cancer treatment method

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

[0001] The present invention relates to a cancer therapeutic agent and a cancer treatment method using the agent.

[0002] Many advanced cancers that are considered incurable, such as gastric cancer, are complicated with peritoneal dissemination. When peritoneal dissemination occurs, it is extremely difficult to completely remove it through surgery, so treatment with anticancer drugs (chemotherapy) is performed. However, when treating peritoneal dissemination, even intravenous systemic administration of anticancer drugs often does not exert sufficient pharmacological effects, and the establishment of new treatment methods is desired.

[0003] In order to solve the above-mentioned problems, Non-Patent Document 1 below describes intraperitoneal chemotherapy in which an anticancer agent such as paclitaxel is directly administered into the peritoneal cavity as a new treatment method for peritoneal dissemination.

[0004] Ishigami H, Fujiwara Y, Fukushima R, et al. Phase III Trial Comparing Intraperitoneal and Intravenous Paclitaxel Plus S-1 Versus Cisplatin 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.

[0005] In intraperitoneal chemotherapy, the interval between intraperitoneal drug administrations is typically about once a week, depending on the type of drug, such as an anticancer drug, used. However, the intraperitoneal residence time of the drug at an effective concentration (drug concentration) at which the drug exerts its efficacy is short, about 24 to 48 hours, and the drug is quickly absorbed and eliminated through the peritoneum, etc.

[0006] In addition, peritoneal dissemination often occurs throughout the abdominal cavity, and to achieve sufficient efficacy, it is necessary to spread the drug administered intraperitoneally evenly over the surface of the affected area to maximize the drug contact area and duration. However, because the drug is liquid and the dosage is limited, it is difficult to spread it widely over the entire inner surface of the abdominal cavity.

[0007] As described above, in intraperitoneal chemotherapy for peritoneal dissemination, it is important to use high concentrations of drugs and allow them to remain and penetrate the entire inner surface of the peritoneal cavity for a long period of time so that effective antitumor effects can be achieved. However, there are issues with drug concentration and drug contact area, as mentioned above, and there is room for improvement.

[0008] At least one embodiment of the present invention has been made in view of the above circumstances, and specifically, an object of the present invention is to provide a cancer therapeutic 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.

[0009] The above object of the present invention is achieved by any one of the following (1) to (18).

[0010] (1) A cancer treatment agent to be administered intraperitoneally, comprising: an anchoring material that has fluidity before administration, and whose fluidity decreases after administration within the abdominal cavity, thereby anchoring to the inner surface of the abdominal cavity; and a drug containing a cancer treatment substance.

[0011] (2) The cancer therapeutic agent according to (1) above, wherein the cancer therapeutic substance is a particulate drug dispersed in a biodegradable material.

[0012] (3) The cancer treatment agent according to (1) or (2), 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.

[0013] (4) The cancer therapeutic agent according to (3) above, wherein the temperature-responsive material changes into a sol or gel within 5 to 15 minutes at temperatures near body temperature.

[0014] (5) The cancer therapeutic agent according to (3) or (4), wherein the temperature-responsive material comprises at least one of an N-substituted (meth)acrylamide derivative, poly(N-acryloylpyrrolidine), a nitrogen-containing cyclic polymer, a vinyl group-containing amino acid or an ester thereof, poly(vinyl methyl ether), poly(ethylene glycol) / poly(propylene glycol), or a polylactic acid-polyglycolic acid-polyethylene oxide copolymer.

[0015] (6) The cancer therapeutic agent according to any one of (1) to (5) above, wherein the drug is decomposed in the abdominal cavity within one to two weeks.

[0016] (7) The cancer therapeutic agent according to any one of (1) to (6) above, wherein the average particle size of the agent is 10 μm or more and 100 μm or less.

[0017] (8) The cancer therapeutic agent according to any one of (1) to (7) above, wherein the biodegradable material contains at least one of lipids, fatty acids, waxes, and derivatives thereof.

[0018] (9) A cancer treatment method, comprising: an administration step of administering a cancer treatment agent containing at least an anchoring material that has fluidity before administration and that decreases in fluidity within the abdominal cavity after administration to anchor to the inner surface of the abdominal cavity, and a drug containing at least a cancer treatment substance, into the abdominal cavity of the patient through an administration tube that is placed within the abdominal cavity and communicates with the outside; and a position change step of changing the patient's position to anchor the cancer treatment agent in the abdominal cavity.

[0019] (10) The cancer treatment method according to (9), wherein the patient's position is changed to at least a supine position, a left lateral position, or a right lateral position.

[0020] (11) The cancer treatment method according to (9) or (10), wherein the patient's position is further changed to at least one of a prone position, a buttocks-furled prone position in which the patient's occiput is lower than the buttocks, and a head-furled prone position in which the patient's occiput is higher than the buttocks.

[0021] (12) A cancer treatment method according to any one of (9) to (11) above, 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.

[0022] (13) The cancer treatment method according to any one of (9) to (12) above, wherein the cancer therapeutic agent is administered into the abdominal cavity while the patient's position is being changed.

[0023] (14) The cancer treatment method according to any one of (9) to (13) above, wherein the procedure for changing the patient's position is carried out for a total of 60 minutes or more per treatment.

[0024] (15) The cancer treatment method according to any one of (9) to (14) above, wherein the drug is in the form of particles in which at least the cancer treatment substance is dispersed in a biodegradable material.

[0025] (16) A cancer treatment method according to any one of (9) to (15) above, wherein the fixing material is a temperature-responsive material that is liquid at temperatures 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 temperatures other than near the body temperature and changes into a gel at near the body temperature.

[0026] (17) A cancer treatment method, comprising: a first administration procedure of administering a fixation material that is to be fixed to the inner surface of the patient's abdominal cavity into the patient's abdominal cavity through an administration tube that communicates with the outside; a second administration procedure of administering a drug containing at least a cancer treatment substance into the patient's abdominal cavity through the administration tube; and a position change procedure of changing the patient's position to apply at least one of the fixation material administered by the first administration procedure and the drug administered by the second administration procedure to the patient's abdominal cavity.

[0027] (18) A cancer treatment method comprising: a first administration procedure of administering a fixation material that is to be fixed to the inner surface of a patient's abdominal cavity into the patient's abdominal cavity through an administration tube that communicates with the outside; a position change procedure of changing the patient's position to apply the fixation material administered by the first administration procedure to the patient's abdominal cavity; and a second administration procedure of administering a drug containing at least a cancer treatment substance into the patient's abdominal cavity through the administration tube after administering the fixation material by the first administration procedure.

[0028] (19) The cancer treatment method according to (17) or (18) above, wherein the fixing material comprises a sol and / or a gel.

[0029] According to the present invention, when administered intraperitoneally, particulate drugs (microspheres) comprising at least a cancer therapeutic substance dispersed in a biodegradable material can be retained in the peritoneum by the use of an anchoring material that has fluidity before administration but decreases in fluidity within the peritoneal cavity after administration and anchors to the inner surface of the peritoneal cavity. Therefore, after administration into the peritoneal cavity, the drug can be sustained and released in a state in which the drug is in contact with the entire peritoneum. This allows the drug's efficacy to be maintained for a long period of time, approximately one to two weeks, after administration, and is therefore expected to have a sufficient therapeutic effect against peritoneal dissemination.

[0030] FIG. 1 is a flowchart showing the procedure of the 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. (a) to (c) are diagrams showing the body positions taken in the body position change procedure. (a) to (c) are diagrams showing the body positions taken in the body position change procedure. FIG. 3 is a diagram showing the state during treatment in the cancer treatment method according to the present embodiment. FIG. 4 is a diagram showing the periphery of a storage section of a bed used in the cancer treatment method according to the present embodiment. FIG. 5 is a diagram showing an example of a form of a protective member used in the cancer treatment method according to the present embodiment. FIG. 6 is a diagram showing another example of a form of a protective member used in the cancer treatment method according to the present embodiment. FIG. 7 is a flowchart showing a modified example of the cancer treatment method according to the present embodiment.

[0031] Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. The embodiments shown here are merely examples for embodying the technical idea of ​​the present invention and are not intended to limit the present invention. Furthermore, all other embodiments, examples, and operational techniques that can be conceived by those skilled in the art without departing from the spirit of the present invention are included in the scope and spirit of the present invention, as well as in the scope of the inventions set forth in the claims and their equivalents.

[0032] Furthermore, for the convenience of illustration and ease of understanding, the drawings attached to this specification may be expressed schematically by appropriately converting 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.

[0033] In the following description, when ordinal numbers such as "first" and "second" are used, unless otherwise specified, they are used for convenience and do not stipulate any particular order.

[0034] [Cancer Therapeutic Agent] The cancer therapeutic agent according to this embodiment will be described.

[0035] The cancer treatment agent is administered into the abdominal cavity A1, and includes an anchoring material that has fluidity before administration, but whose fluidity decreases within the abdominal cavity A1 over a predetermined period of time after administration, causing the agent to anchor to the inner surface of the abdominal cavity A1 (such as the peritoneum A4 and surrounding organs), and a drug containing a cancer treatment substance. The cancer treatment substance includes a particulate drug dispersed in a biodegradable material.

[0036] The cancer therapeutic agent can effectively treat and / or prevent peritoneal dissemination that occurs in organs present in the abdominal cavity A1, such as stomach cancer, colon cancer, liver cancer, gallbladder cancer, pancreatic cancer, kidney cancer, etc.

[0037] <Anchoring material> The anchoring material has fluidity when administered into the abdominal cavity A1, and after a predetermined time has passed, the fluidity decreases and the anchoring material becomes anchorable to the inner surface of the abdominal cavity A1. Here, "fluidity decreases" means that the anchoring material is in a state where it can be anchored to the inner surface of the abdominal cavity A1, and includes a state where it has changed into a solid state or a state where it is in a liquid state but has a high viscosity and can adhere to the abdominal cavity A1.

[0038] 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 therapeutic agent is administered into the abdominal cavity A1, the fluidity of the agent gradually decreases as the drug temperature approaches near body temperature, at which 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.

[0039] The temperature-responsive material preferably changes into a sol or gel at about body temperature within 5 to 15 minutes. This time is the time required for the cancer treatment agent administered into the abdominal cavity A1 in a fluid state to be distributed throughout the abdominal cavity A1 while changing the position of the 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 the abdominal cavity A1 by changing the position of the patient P within the aforementioned time period in which the fluidity of the agent decreases after administration into the abdominal cavity A1, and after the fluidity of the agent decreases and the agent becomes fixed.

[0040] 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), and polylactic acid-polyglycolic acid-polyethylene oxide copolymers. The temperature-responsive material may be any material that has fluidity at least before administration and whose fluidity decreases at temperatures around body temperature after administration into the abdominal cavity A1. For example, materials disclosed in JP-A-2000-080158 and JP-A-2005-239860 can be suitably used.

[0041] In addition to temperature-responsive gels, the fixing material may also be a gel whose fluidity decreases due to factors other than heat, such as a stimulus-responsive gel (stimuli such as pH changes) or a molecular stimulus-responsive gel (a gel that swells and shrinks in response to recognizing specific molecules).

[0042] <Drug> The drug is composed of at least a cancer therapeutic 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 therapeutic substance), and an appropriately adjusted additive, solvent, etc. By forming the drug into microspheres, the initial release amount of the cancer therapeutic substance and the release rate during the subsequent release period can be appropriately controlled, allowing for sustained release in the body for a certain period of time.

[0043] A cancer therapeutic substance refers to a substance such as an anticancer drug that has a cytocidal effect, such as destroying or killing cancer cells. The cancer therapeutic substance may be an 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), Opdivo (active ingredient: nivolumab (genetical recombination)), and cabazitaxel (active ingredient: cabazitaxel). acetone adduct), carboplatin (active ingredient: carboplatin), gemcitabine (active ingredient: gemcitabine hydrochloride), Cyramza (active ingredient: ramucirumab (genetical recombination)), Gemzar (active ingredient: gemcitabine hydrochloride), cyclophosphamide (active ingredient: cyclophosphamide hydrate), cisplatin (active ingredient: cisplatin), cytarabine (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 Suitable cancer therapeutic agents include emtansine (genetical recombination), nimustine (active ingredient: nimustine hydrochloride), nedaplatin (active ingredient: nedaplatin), nogitecan (active ingredient: nogitecan hydrochloride), Perjeta (active ingredient: pertuzumab (genetical recombination)), panitumumab (active ingredient: panitumumab (genetical recombination)), vinorelbine (active ingredient: vinorelbine tartrate), vincristine (active ingredient: vincristine sulfate), and fluorouracil (active ingredient: fluorouracil). One or more cancer therapeutic agents may be used, or two or more may be used in combination. The dose of the cancer therapeutic agent varies depending on the type of cancer and the type of cancer used, and can be determined by appropriately selecting a dose generally used for treatment.

[0044] The biodegradable material used in the drug has biodegradability and the property of allowing the cancer treatment substance to be dispersed. 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). Furthermore, the biodegradable material may be any material that does not inhibit the sustained release or efficacy of the cancer treatment substance or has very little risk of inhibiting this. Suitable examples of the biodegradable material include those disclosed in JP 2005-35994 A and the like.

[0045] 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 range of average particle size is the size necessary to obtain a sufficient drug concentration and appropriate sustained release when the efficacy of the cancer therapeutic agent 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, etc.

[0046] Furthermore, a mixture of drugs with different average particle sizes can be used to adjust the sustained release period. In this case, the drugs may be of the same type or different types may be used in combination.

[0047] As described above, when administered into the abdominal cavity A1, the cancer treatment agent according to this embodiment has fluidity before administration, but after administration, the fluidity decreases within the abdominal cavity A1, and the agent adheres to the inner surface of the abdominal cavity A1, allowing the particulate drug (microspheres) comprising at least a cancer treatment substance dispersed in a biodegradable material to remain in the peritoneum due to the action of the adhesive material. Therefore, after administration into the abdominal cavity A1, the cancer treatment agent can sustainably release the drug at a concentration sufficient to obtain its efficacy over a long period of time while ensuring that the drug is in contact with the entire abdominal cavity A1. Therefore, the efficacy of the cancer treatment agent can be maintained for a long period of time, approximately one to two weeks, after administration.

[0048] The cancer therapeutic 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 fixable material. Therefore, the cancer therapeutic agent is in the form of a mixture of at least the fixable material and the drug, but as in a modified example of the cancer treatment method described below, the fixable material may be administered first, and then the drug may be administered before the fixable material is fixed within the abdominal cavity A1. In other words, the fixable material and the drug may be mixed immediately before the administration procedure described below.

[0049] [Cancer Treatment Method] Next, a cancer treatment method using the above-mentioned cancer treatment agent will be described.

[0050] 1 , the cancer treatment method includes an arrangement step S1 of arranging an administration tube 10 communicating with the outside into 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 an anchoring material that has fluidity before administration and whose fluidity decreases in the abdominal cavity A1 after administration so that the anticancer agent anchors to the inner surface of the abdominal cavity A1 (such as the peritoneum A4 and surrounding organs) via the administration tube 10 into the abdominal cavity A1 of the patient P, and a position change step S3 of changing the position of the patient P to allow the cancer treatment agent to anchor 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.

[0051] <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 is performed, and can be performed before the cancer treatment method is performed.

[0052] 2, the administration tube 10 includes a tube body 11, an internally fixed part 12, an externally fixed part 13, a connecting part 14, and a lid part 15. The administration tube 10 is attached with a portion thereof being retained in the abdominal cavity A1 of a patient P, and is used when administering a cancer therapeutic agent into the abdominal cavity A1. The administration tube 10 is fixed in a state in which the internally fixed part 12 and the externally fixed part 13 sandwich the biological tissue between the skin A2 and the peritoneum A4.

[0053] The tube body 11 is a flexible hollow member having a cavity formed from the distal end to the proximal end. The distal end of the tube body 11 is disposed within the abdominal cavity A1, and the proximal end is disposed outside the living body.

[0054] The internally fixed part 12 is disposed on the distal end side of the tube body 11 and is used to fix the administration tube 10 to a living body. The internally fixed part 12 can be configured, for example, by a balloon having an internal space (lumen) into which a pressurized medium (e.g., a fluid such as physiological saline or air) used for inflation flows, or a hollow, disk-shaped bumper formed integrally with the outer circumferential surface of the tube body 11. Figure 2 shows an internally fixed part 12 formed from a balloon.

[0055] The internally fixed part 12 may have any shape that allows the distal end of the tube body 11 to be placed and fixed within the abdominal cavity A1. The internally fixed part 12 may be a balloon type, a bumper type, or a shape that expands after placement in the body to fix the tube body 11, like a self-expanding stent, or a combination of these shapes may be used. Furthermore, the internally fixed part 12 may additionally be provided with a 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.

[0056] The external fixing part 13 is a small piece extending in a direction intersecting the axial direction of the tube body 11 inserted through the perforation hole A3. The external fixing part 13 is placed in contact with the outer surface of the epidermis of the skin A2. The external fixing part 13 prevents the administration tube 10 from being buried in the perforation hole A3 and from being displaced.

[0057] The connection part 14 is composed of a connector disposed in communication with the base end of the tube main 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 therapeutic 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, allowing the cancer therapeutic agent in the infusion bag 200 to flow into the abdominal cavity A1 of the patient P. The shape of the connection part 14 is not limited as long as it is at least detachable from the external connector 101 and has a locking function to maintain the connection state.

[0058] 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 therapeutic 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.

[0059] 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 intentionally released. Therefore, the administration tube 10 does not have to worry about the needle being accidentally removed when changing position, which can occur with the puncture method. Note that the administration tube 10 is not limited to being fixed by the internal fixation part 12 and the external fixation part 13, and can also be placed in the skin as a subcutaneously implanted intradermal port. Furthermore, the administration tube 10 may include a needle in addition to the tube main body 11.

[0060] Administration procedure S2 is an operation of 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 containing a cancer therapeutic substance, and therefore, after a predetermined time has passed after administration, the cancer therapeutic agent anchors to the surface of the peritoneum A4 within the abdominal cavity A1.

[0061] The administration timing in the administration procedure S2 can be before the start of the position change procedure S3 or can be synchronized with the start of the position change procedure S3. That is, the administration procedure S2 can be performed immediately before the position change procedure S3 is performed or during the position change procedure S3 (while the position is being changed). Furthermore, the dose of the cancer therapeutic agent in the administration procedure S2 is not particularly limited and can be set appropriately. For example, the dose of the cancer therapeutic agent can be set based on the number of position changes in the position change procedure S3. After the start of the position change procedure S3, the same amount can be administered in equal portions equal to the number of position changes, or the cancer therapeutic agent can be administered continuously from the start to the end of the position change procedure S3. For example, if the position is changed three times in the position change procedure S3, one-third of the total dose can be administered each time the position is changed.

[0062] <Position Change Procedure> The position change procedure S3 is an operation for changing the position of the patient P so that the cancer treatment agent administered in the administration procedure S2 is evenly distributed throughout the abdominal cavity A1. The position change procedure S3 adheres the cancer treatment agent administered into the abdominal cavity A1 to the inner surface of the abdominal cavity A1, and fixes the cancer treatment 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.

[0063] 3 and 4 show the positions to be changed in the position changing procedure S3.

[0064] The position change procedure S3 includes operations for changing the basic position to the supine position, left lateral position, and right lateral position, as shown in Fig. 3 . The supine position is the position (posture) in which the patient P lies on the bed 300. The supine position is the position in which the 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 the 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 the patient P lies on the bed 300 with his / her left arm underneath, as shown in Fig. 3(c).

[0065] The position change procedure S3 may change the patient P to the positions shown in Fig. 4 in addition to the supine position, left lateral position, and right lateral position shown in Fig. 3 . Specifically, the position change procedure S3 includes operations for changing the patient P 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 occipital region 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 occipital region higher than the buttocks, as shown in Fig. 4(c). The buttocks-flip supine position and the head-flip supine position may be performed with the patient P lying face down on the bed 300 .

[0066] In the position change procedure S3, a position retention time for maintaining the position can be set according to the settling time of the fixative material of the cancer therapeutic agent to be administered (the time from the start of administration until the fluidity reaches its lowest point after administration). For example, if the settling time of the fixative material contained in the cancer therapeutic 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 therapeutic agent adhering to the abdominal cavity A1 can be set to settle when the position is maintained.

[0067] The timing of the position change procedure S3 can be set appropriately according to the settling time of the fixing material of the cancer treatment agent to be administered (the time from the start of administration until the fluidity reaches its lowest after administration).

[0068] In the flowchart shown in FIG. 1 , the administration procedure S2 and the position change procedure S3 are each performed once, but the administration procedure S2 and the position change procedure S3 can be repeated alternately a predetermined number of times in one treatment. One treatment is a cancer treatment that includes 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, the following steps are performed: first, a predetermined amount of the cancer therapeutic agent is administered by the first administration procedure S2 (e.g., ¼ of the total daily dose) → the patient is maintained in a supine position by the first position change procedure S3 for 15 minutes → a predetermined amount of the cancer therapeutic agent is administered by the second administration procedure S2 (e.g., ¼ of the total daily dose) → the patient is maintained in a supine position by the second position change procedure S3 The patient is changed from the supine position to the left lateral position and held for 15 minutes → a predetermined amount of the cancer therapeutic agent is administered in a third administration procedure S2 (e.g., ¼ of the total daily dose) → the patient is changed from the left lateral position to the right lateral position and held for 15 minutes in a third position change procedure S3 → a predetermined amount of the cancer therapeutic agent is administered in a fourth administration procedure S2 (e.g., ¼ of the total daily dose) → the patient is changed from the right lateral position to the prone position and held for 15 minutes in a fourth position change procedure S3. In this way, by repeating the administration procedure S2 and the position change procedure S3 multiple times, the cancer therapeutic agent can be more effectively distributed throughout the inner surface of the abdominal cavity A1.

[0069] As shown in FIGS. 5A and 5B, a bed 300 used in the cancer treatment method is provided with a storage section 310.

[0070] The storage section 310 has a form that can store components 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 components 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 position and changes 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 of the patient P during the position change procedure, and also prevents incomplete administration of the cancer therapeutic agent due to crushing of the external tube 100, damage to the external tube 100, etc.

[0071] 6A , it is effective to attach a protective member 110 that covers the outer circumferential surface of the external tube 100. 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.

[0072] The protective member 110 can be configured as a protective cover 110A, which is a cylindrical member made of an elastic member and has a slit in the lumen through which the external tube 100 can be inserted and removed, as shown in Fig. 6A, or a protective coil 110B, which is spirally wound 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, and may be any form that can prevent the external tube 100 from being crushed or damaged.

[0073] In the position change procedure S3, the patient P may assume a position in which the abdomen faces the bed 300, such as in the prone position, so 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.

[0074] Next, a modified example of the cancer treatment method according to this embodiment will be described.

[0075] The modified cancer treatment method differs from the modified cancer treatment method in the administration procedure S2 between the placement procedure S1 and the position change procedure S3 shown in Fig. 1. As shown in Fig. 7, the modified cancer treatment method includes a placement procedure S11, a first administration procedure S12 for administering an anchoring material, a position change procedure S13, and a second administration procedure S14 for administering a drug containing at least an anticancer drug. The placement procedure S11 is the same as the placement procedure S1 shown in Fig. 1 described above, and therefore will not be described further.

[0076] In the modified cancer treatment method, the fixing material and the drug contained in the cancer treatment agent are administered separately, as in the cancer treatment method described above.

[0077] <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 forms the inner surface of the abdominal cavity A1, and the surfaces of the surrounding organs.

[0078] <Position Change Procedure> The position change procedure S13 is an operation for changing the position of the patient P to distribute 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 distributed throughout the entire abdominal cavity A1. Note that the first administration procedure S12 and the position change procedure S13 can be repeated multiple times while changing the patient's position to efficiently distribute the fixing material throughout the entire abdominal cavity A1.

[0079] <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 after the fixing material has settled. 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, settles on the inner surface of the abdominal cavity A1 as the fluidity of the fixing material decreases. 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 settles (before the fixing material settles on the inner surface of the abdominal cavity A1 due to the decrease in fluidity of the fixing material).

[0080] In the modified cancer treatment method, the patient P's position is changed to distribute the fixation material throughout the inner surface of the abdominal cavity A1, and then a drug is administered in the second administration procedure S14. This allows the drug to mix with the previously administered fixation material and remain within the peritoneum A4, the inner surface of the abdominal cavity A1, and the surrounding organs. If the second administration procedure S14 is performed after the first administration procedure S12 is performed to administer the fixation material and the fixation material has settled, the settled fixation material acts as a semipermeable membrane, allowing the drug to diffuse through the settled fixation material, thereby remaining within the peritoneum A4, 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 first administration procedure S12 is performed to administer the fixation material and before the fixation material settles (before the fixation material settles within the inner surface of the abdominal cavity A1 due to a decrease in the fluidity of the fixation material), the temperature of the fixation material reaches near body temperature, and the fluidity of the fixation material containing the drug decreases, allowing the fixation material to settle within the inner surface of the abdominal cavity A1. As the fluidity of the drug-containing fixative material decreases, it settles on the inner surface of the abdominal cavity A1, allowing it to remain in the peritoneum A4, which is the inner surface of the abdominal cavity A1, and the surrounding organs. Drugs have lower viscosity than fixative materials and are easily absorbed by the peritoneum A4, but by administering the drug after applying the fixative material to the abdominal cavity A1 in advance, the effect of the fixative material allows the drug to remain in the body for a long time. Furthermore, compared to changing the patient's position while administering the drug, there is a lower risk of the tube coming loose and the risk of drug exposure is also reduced. Furthermore, there is no need to use microspheres or other liquid medications, and existing medications made by mixing saline with anticancer drugs can be used, broadening the range of drugs that can be used.

[0081] 7, the order of the position change procedure S13 and the second administration procedure S14 may be reversed, such as the first administration procedure S12 → the second administration procedure S14 → the position change procedure S13, or the second administration procedure S14 may be performed before the first administration procedure S12. In either case, the drug and the fixing material can be mixed in the abdominal cavity A1 and adhered to the inner surface of the abdominal cavity A1 during the position change in the position change procedure S13. Furthermore, the first administration procedure S12, the position change procedure S13, and the second administration procedure S14 may be repeated as necessary. That is, the modified cancer treatment method may include a first administration procedure S12 of administering a fixing material that is to be fixed to the inner surface of the abdominal cavity A1 of the patient P into the abdominal cavity A1 of the patient P via an administration tube 10 that communicates with the outside inside the abdominal cavity A1 of the patient P, a second administration procedure S14 of administering a drug containing at least a cancer treatment substance into the abdominal cavity A1 of the patient P via the administration tube 10, and a position change procedure S13 of changing the position of the patient P 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 inside of the abdominal cavity A1 of the patient P.

[0082] As described above, the cancer treatment agent of 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 within the abdominal cavity A1 after administration, causing it to anchor to the inner surface of the abdominal cavity A1, and a drug containing a cancer treatment substance.

[0083] Furthermore, the cancer treatment method according to this embodiment includes an administration procedure S2 in which a cancer treatment agent containing at least an anchoring material that has fluidity before administration and that decreases in fluidity within the abdominal cavity A1 after administration to anchor to the inner surface of the abdominal cavity A1, and a drug containing at least a cancer treatment substance, is administered into the abdominal cavity A1 of the patient P via 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 procedure S3 in which the position of the patient P is changed to allow the cancer treatment agent to anchor within the abdominal cavity A1.

[0084] With this configuration, the cancer therapeutic agent can be administered into the abdominal cavity A1 and retained in the peritoneum A4, which is the inner surface of the abdominal cavity A1, and in the surrounding organs while the patient is being changed to a predetermined position, so that the agent can be kept in contact with the entire surface of the peritoneum A4 and sustained release for a longer period of time than with conventional treatment methods. Therefore, according to the cancer therapeutic agent and cancer treatment method using this therapeutic agent of this embodiment, the efficacy of the cancer therapeutic agent after administration is maintained for a long period of time, about one to two weeks, and a sufficient therapeutic effect against peritoneal dissemination can be obtained.

[0085] 10 Administration tube, 11 Tube body, 12 Internal fixation part, 13 External fixation part, 14 Connection part, 15 Lid part, 100 External tube, 101 External connector, 110 Protective member, 110A Protective cover, 110B Protective coil, 200 Infusion bag, 300 Bed, 310 Storage part A1 Abdominal cavity, A2 Skin, A3 Perforation hole, A4 Peritoneum P Patient.

Claims

1. A cancer treatment agent to be administered into the abdominal cavity, 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 containing a cancer treatment substance.

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

3. 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.

4. The cancer treatment agent according to claim 3, wherein the temperature-responsive material changes into a sol or gel within 5 to 15 minutes at approximately body temperature.

5. The cancer treatment agent according to claim 2, wherein the temperature responsive material comprises at least one of N-substituted (meth)acrylamide derivatives, poly(N-acryloylpyrrolidine), nitrogen-containing cyclic polymers, vinyl group-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. The cancer therapeutic agent according to claim 1, wherein the drug is decomposed in the abdominal cavity within a period of 1 to 2 weeks.

7. The cancer therapeutic agent according to claim 1, wherein the average particle size of the drug is 10 μm or more and 100 μm or less.

8. The cancer treatment agent according to claim 1, wherein the biodegradable material includes at least one of lipids, fatty acids, waxes, and derivatives thereof.

9. A method for treating cancer, comprising: an administration step of administering a cancer therapeutic agent containing at least a fixing material which has fluidity before administration and which after administration becomes fluid within the abdominal cavity and fixes to the inner surface of the abdominal cavity as a result, and a drug containing at least a cancer therapeutic substance, into the abdominal cavity of a patient through an administration tube which is placed within the abdominal cavity of the patient and communicates with the outside; and a position changing step of changing the position of the patient to fix the cancer therapeutic agent in the abdominal cavity.

10. The method for treating cancer according to claim 9, wherein the patient's body 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 claim 10, wherein the patient's position is further changed to at least one of a prone position, a buttocks-fisted prone position in which the patient's back of the head is lower than the buttocks, and a head-fisted prone position in which the patient's back of the head is higher than the buttocks.

12. A 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.

13. The method of cancer treatment according to claim 9, wherein the cancer therapeutic agent is administered into the abdominal cavity while the patient's position is changed.

14. The cancer treatment method according to claim 9, wherein the patient repositioning procedure is performed for a total of 60 minutes or more per treatment.

15. The cancer treatment method according to claim 9, wherein the drug is in the form of particles in which at least the cancer treatment substance is dispersed in a biodegradable material.

16. The cancer treatment method of 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 patient's body temperature and changes into a gel at near the body temperature.

17. A method for treating cancer, comprising: a first administration step of administering a fixation material that is to be fixed on the inner surface of the patient's abdominal cavity into the patient's abdominal cavity through an administration tube that communicates with the outside; a second administration step of administering a drug containing at least a cancer therapeutic substance into the patient's abdominal cavity through the administration tube; and a position change step of changing the patient's position to apply at least one of the fixation material administered by the first administration step and the drug administered by the second administration step to the inside of the patient's abdominal cavity.

18. The cancer treatment method of claim 17, wherein the fixing material comprises a sol and / or a gel.

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