JP6143169B2 - Pancreatic cancer therapeutic agent - Google Patents

Description

  The present invention relates to a therapeutic agent for pancreatic cancer, particularly a therapeutic agent for advanced pancreatic cancer, characterized by combining a plurality of GSK3β inhibitors with gemcitabine which is an active ingredient.

(Pancreatic cancer)
Pancreatic malignant tumors, 80-90% are pancreatic ductal carcinomas that originate from the pancreatic ductal epithelium of the exocrine pancreas. Many pancreatic ductal cancers are small tubular adenocarcinomas and are highly malignant. Attempts have been made to add multidisciplinary treatments such as intraoperative radiation therapy, chemotherapy, hyperthermia, and immunotherapy to extended surgery, but the results are very poor compared to other gastrointestinal cancers.

(GSK3β inhibitor)
A GSK3β inhibitor means a substance or compound that physically or chemically inhibits the function of GSK3β. Many compounds have already been identified for such GSK3β inhibitors, but their structures and action mechanisms are diverse (see Non-Patent Document 1).
The activity of GSK3β is in various stages: (a) post-translational modification (control by phosphorylation of post-translation 9th serine and 216 tyrosine residues), (b) interaction with protein complex, (c) substrate priming (D) Intracellular localization is controlled, and the above-mentioned GSK3β inhibitor seems to act on GSK3β at any stage (see Non-Patent Document 1).

  Patent Document 1 discloses “a brain tumor therapeutic agent in combination with a GSK3β inhibitor”. However, this document does not disclose or suggest a method for treating pancreatic cancer, or further administration of gemcitabine.

(Gemcitabine)
Gemcitabine is a cytidine analog (2 ′, 2′-difluorodeoxycytidine) and is widely used in the treatment of various cancers. Gemcitabine is also a standard treatment for pancreatic cancer. However, the survival rate after 1 year of patients with pancreatic cancer is about 18%, and there is a limit to the effect of using gemcitabine alone.

(Combination administration of anticancer drugs)
The combined administration treatment of an anticancer agent or the combination treatment of an anticancer agent and radiation therapy for improving the low survival rate described above improves the therapeutic effect by eliminating the limit of a large amount of single anticancer agent used. It has been reported that the killing effect of tumor cells is significantly increased by combining therapeutic agents or treatment methods for specific cancers.
Therefore, development of a method for treating cancer using a combination of new anticancer agents is desired.

  Patent Document 2 discloses “a method of administering glufosfamide and gemcitabine in combination to a subject in need of treatment for pancreatic cancer”. However, this document does not disclose or suggest that a GSK3β inhibitor is used in combination.

Meijer L, Flajolet M, Greengard P. Trends in Pharmacol Sci 2004; 25 (9): 471-80

JP 2013-41314 A JP 2012-64002 JP

  As described above, pancreatic cancer, particularly advanced pancreatic cancer, has a fast progression, a very poor prognosis, and a high degree of malignancy. Actual tumors often cannot be completely removed by surgery, are resistant to existing anticancer drug treatment and radiation treatment, and are extremely refractory. Thus, since there is no effective treatment for this tumor, its life prognosis has not been improved, and development of a new therapeutic agent for advanced pancreatic cancer is eagerly desired.

  In order to solve the above problems, the present inventors have provided a therapeutic agent for pancreatic cancer and a kit for treating pancreatic cancer, characterized in that gemcitabine is administered in combination with a plurality of GSK3β inhibitors.

That is, the present invention is characterized by the following as a solution to the above problems.
“1. A therapeutic agent for pancreatic cancer comprising a combination of gemcitabine as an active ingredient, cimetidine as an active ingredient, and sodium valproate as an active ingredient.
2. The pancreatic cancer therapeutic agent according to claim 1, wherein the pancreatic cancer therapeutic agent is a progressive pancreatic cancer therapeutic agent.
3. The therapeutic agent for pancreatic cancer according to item 1 or 2, characterized by being in the following dosage form:
(1) Gemcitabine: 100 to 1500 mg / m ² once a week for 3 consecutive weeks, 4 weeks off, or once a week for 2 consecutive weeks, 3 weeks off
(2) Cimetidine: 100 to 3200 mg divided into two doses per day, administered daily, administered once every few days, or administered every other week,
(3) Sodium valproate: 100 to 3000 mg divided into two times a day, administered daily, once a few days or several times every other week.
4). 4. The therapeutic agent for pancreatic cancer according to any one of items 1 to 3, further comprising olanzapine as an active ingredient in combination.
5. The therapeutic agent for pancreatic cancer according to item 4 above, which is a dosage form in which 5 to 60 mg of olanzapine is administered daily, administered once every few days, or administered several times every other week.
6). 6. The therapeutic agent for pancreatic cancer according to any one of 1 to 5 above, wherein the progressive pancreatic cancer is progressive pancreatic cancer accompanied by diabetes.
7). A kit for treating pancreatic cancer comprising gemcitabine as an active ingredient, cimetidine as an active ingredient, and sodium valproate as an active ingredient.
8). 8. The agent for treating pancreatic cancer according to item 7 above, wherein the kit for treating pancreatic cancer is a kit for treating advanced pancreatic cancer.
9. 9. The kit for treating pancreatic cancer according to 7 or 8 above, further comprising olanzapine as an active ingredient. "

The pancreatic cancer therapeutic agent and pancreatic cancer treatment kit of the present invention not only delayed and stopped the progression of progressive pancreatic cancer, which was very difficult to stop the progression, but also reduced the tumor.
That is, the therapeutic agent for progressive pancreatic cancer and the kit for treating progressive pancreatic cancer of the present invention showed a remarkable effect as compared with the conventional therapeutic agent for pancreatic cancer.

Change of CA19-9 value which is cancer marker of clinical case 1 (GEM 3W1R is "Gemcitabine is administered once a week for 3 consecutive weeks, 4 weeks are withdrawn, and this is repeated as a course." Means) Change of CA19-9 value and Span-1 value which are cancer markers of clinical case 2 Change of CA125 value which is cancer marker of clinical example 3 Change in SUVmax value as a cancer marker in clinical case 3 CT image of clinical case 3

  The present invention relates to “a pancreatic cancer therapeutic agent and a pancreatic cancer treatment kit, as well as a progressive pancreatic cancer therapeutic agent and a progressive pancreatic cancer treatment kit”. Embodiments of the present invention will be described below.

The therapeutic agent for pancreatic cancer and the kit for treating pancreatic cancer of the present invention (particularly, the therapeutic agent for progressive pancreatic cancer and the kit for treating progressive pancreatic cancer) reduce the size of cancer tissue and / or tumor, maintain tumor cells, Providing to stop, delay and / or extinguish growth.
Reduction in tumor size and / or inhibition of growth can be measured by response criteria (RECIST) guidelines in solid tumors.

The term “advanced pancreatic cancer patient” in the present invention is intended for mammals including humans who have been clinically diagnosed as having advanced stage (sex). The advanced pancreatic cancer patients include recurrent pancreatic cancer, metastatic pancreatic cancer, and chemotherapy-resistant pancreatic cancer.
In addition, the clinically advanced stage (sex) diagnosis method can be a method known per se, and can be determined based on, for example, “Pancreatic Cancer Handling Rules published by the Pancreatic Society of Japan”.
Furthermore, the following disease patients are targeted as necessary.
(1) Age is 15 years old or older and 90 years old or younger.
(2) There is no allergy to the administered drug.
(3) Have appropriate organ function.
(4) There is no medical condition that prevents taking oral medicine.

(GSK3β inhibitor)
The GSK3β inhibitors used in the present invention are listed below, but GSK3β inhibitors having the same mechanism of action as the following GSK3β inhibitors can also be used.
(1) cimetidine (2) sodium valproate (3) olanzapine (4) lithium carbonate

(Treatment agent for pancreatic cancer)
The “pancreatic cancer therapeutic agent (particularly, progressive pancreatic cancer therapeutic agent)” of the present invention is characterized by combining gemcitabine as an active ingredient, cimetidine as an active ingredient, and sodium valproate as an active ingredient, and more preferably Is a therapeutic agent characterized by combining olanzapine which is an active ingredient. In addition, it is a therapeutic agent characterized by combining a lithium carbonate preparation as necessary.

(Gemcitabine)
The administration method of gemcitabine in the pancreatic cancer therapeutic agent and pancreatic cancer treatment kit (particularly, the progressive pancreatic cancer therapeutic agent and the progressive pancreatic cancer treatment kit) of the present invention can be appropriately set with reference to the following.
(1) Non-small cell lung cancer, pancreatic cancer, biliary tract cancer, urothelial cancer, ovarian cancer that worsened after cancer chemotherapy Usually, for adults, 1000 mg / m ² as gemcitabine is infused intravenously over 30 minutes. Once a week, administration is continued for 3 weeks. This is repeated as one course. The dose may be reduced according to the patient's condition.
(2) Inoperable or recurrent breast cancer In general, for adults, 1250 mg / m ² of gemcitabine is infused intravenously over 30 minutes, once a week for 2 consecutive weeks, and 3 weeks off. . Repeat this administration as a course. The dose may be reduced according to the patient's condition.
Gemcitabine is sold by Eli Lilly Japan as Gemzar ^(R) .

(Cimetidine)
The administration method of cimetidine in the pancreatic cancer therapeutic agent and pancreatic cancer treatment kit (particularly, the progressive pancreatic cancer therapeutic agent and the progressive pancreatic cancer treatment kit) of the present invention can be appropriately set with reference to the following.
Generic name: Cimetidine (JAN)
Chemical name: 2-cyano-1-methyl-3- {2-[(5-methyl-1H-imidazol-4-yl) methylsulfanyl] ethyl} guanidine
Molecular formula: C ₁₀ H ₁₆ N ₆ S
Molecular weight: 252.34
Indications: Gastric ulcer, duodenal ulcer, anastomotic ulcer, Zollinger-Ellison syndrome, reflux esophagitis, upper gastrointestinal bleeding (due to peptic ulcer, acute stress ulcer, hemorrhagic gastritis), acute gastritis, acute exacerbation of chronic gastritis Of gastric mucosal lesions (erosion, bleeding, redness, edema) in the childhood (use / dose for gastric ulcer and duodenal ulcer)
Usually, for adults, 800 mg of cimetidine is orally administered in two divided doses (after breakfast and before going to bed). In addition, the daily dose can be divided into four times (after each meal and before going to bed) or administered once (before going to bed). The dosage may be adjusted according to age and symptoms.
{Dosage and administration of anastomotic ulcer, Zollinger-Ellison syndrome, reflux esophagitis, upper gastrointestinal bleeding (due to peptic ulcer, acute stress ulcer, hemorrhagic gastritis)}
Usually, for adults, 800 mg of cimetidine is orally administered in two divided doses (after breakfast and before going to bed). In addition, the daily dose can be divided into four doses (after each meal and before going to bed). The dosage may be adjusted according to age and symptoms. However, in the case of upper gastrointestinal bleeding, treatment is usually started with an injection and switched to oral administration after it becomes available.
{Dosage and administration for improvement of gastric mucosal lesions (erosion, bleeding, redness, edema) during acute exacerbation of acute gastritis and chronic gastritis}
In general, for adults, 400 mg daily as cimetidine is orally administered in divided doses (after breakfast and before going to bed). A daily dose can also be administered once (before going to bed). The dosage may be adjusted according to age and symptoms.
Cimetidine is a compound known per se and is manufactured and sold as Tagamet ^(R) tablet by Dainippon Sumitomo Pharma Co., Ltd.
In addition, cimetidine injection (Dainippon Sumitomo Pharma Co., Ltd.) can also be used.

(Sodium valproate)
The administration method of sodium valproate in the pancreatic cancer therapeutic agent and pancreatic cancer treatment kit (particularly, the progressive pancreatic cancer therapeutic agent and the progressive pancreatic cancer treatment kit) of the present invention can be appropriately set with reference to the following.
Generic name: Sodium Valproate
Chemical name: Monosodium 2-propylpentanoate
Molecular formula: C ₈ H ₁₅ NaO ₂
Molecular weight: 166.19
Indications: Treatment of various types of epilepsy (small seizures, focal seizures, psychomotor seizures, and mixed seizures) and personality behavioral disorders associated with epilepsy (such as moodiness and anger). Treatment of mania and manic depression.
Dosage and administration: The usual daily dose of sodium valproate 400-1200 mg is orally administered in 1 to 2 divided doses per day. However, the dose may be adjusted according to the age and symptoms.
Sodium valproate is a compound known per se and is manufactured and sold as Depaken ^(R) by Kyowa Hakko Kirin Co., Ltd.
In addition, sodium valproate sustained-release granules (Daiichi Sankyo Co., Ltd.), sodium valproate syrup (Nippon Pharma Co., Ltd.), and sodium valproate fine granules (Elmed Eisai Co., Ltd.) are also available.

(Olanzapine)
The administration method of olanzapine in the pancreatic cancer therapeutic agent and pancreatic cancer treatment kit (particularly, the progressive pancreatic cancer therapeutic agent and the progressive pancreatic cancer treatment kit) of the present invention can be appropriately set with reference to the following.
Generic name: Olanzapine (JAN)
Chemical name: 2-methyl-4- (4-methylpiperazin-1-yl) -10H-thieno [2,3-b] [1,5] benzodiazepine
Molecular formula: C ₁₇ H ₂ 0N ₄ S
Molecular weight: 312.43
Indications: Schizophrenia Directions / Dosage: In general, for adults, 5-10 mg of olanzapine is started by oral administration once a day. The maintenance dose is 10 mg orally once a day. The dosage may be adjusted according to age and symptoms.
Olanzapine is a compound known per se and is manufactured and sold as Zyprexa ^(R) tablet by Eli Lilly Japan.

(Lithium carbonate)
The administration method of lithium carbonate in the pancreatic cancer therapeutic agent and pancreatic cancer treatment kit (particularly, the progressive pancreatic cancer therapeutic agent and the progressive pancreatic cancer treatment kit) of the present invention can be appropriately set with reference to the following.
Generic Name: Lithium Carbonate (JAN)
Chemical name: lithium carbonate
Molecular formula: Li ₂ CO ₃
Molecular weight: 73.89
Efficacy / Effects: Manic and Manic Depressive Situation Usage / Dose: Lithium carbonate usually starts at 400-600 mg / day for adults and is taken orally in divided doses 2-3 times a day. Thereafter, the dose is gradually increased up to 1200 mg per day, usually every 3 days to 1 week. If improvement is observed, gradually observe the symptom and gradually reduce the maintenance dose to 200 to 800 mg / day in 1 to 3 divided oral doses. The dosage may be adjusted according to age and symptoms.
Lithium carbonate is a compound known per se and is manufactured and sold as a Remus ^(R) tablet by Taisho Pharmaceutical Co., Ltd.

(Pancreatic cancer treatment kit of the present invention)
The kit for treating pancreatic cancer of the present invention (especially a kit for treating advanced pancreatic cancer) can be administered with the active ingredients gemcitabine, olanzapine, cimetidine, sodium valproate and lithium carbonate simultaneously, separately or sequentially. Therefore, each active ingredient is separately stored in a plurality of containers, or each active ingredient is stored in one container having a plurality of regions that can be spatially separated.
Furthermore, the kit for treating pancreatic cancer of the present invention may include instructions regarding administration of each active ingredient. In addition, this instruction | indication describes the administration schedule of each active ingredient in the pancreatic cancer treatment method of this invention shown below.
In particular, each active ingredient in the pancreatic cancer treatment kit of the present invention is preferably an orally administrable tablet, but can be a sustained-release granule, syrup, fine granule, and / or injection.

(Treatment method using pancreatic cancer therapeutic agent and pancreatic cancer treatment kit of the present invention)
In the therapeutic method using the therapeutic agent for pancreatic cancer and the kit for treating pancreatic cancer (particularly, the therapeutic agent for pancreatic cancer and the kit for treating progressive pancreatic cancer) of the present invention, gemcitabine, olanzapine, cimetidine, sodium valproate, and lithium carbonate The dose, frequency and interval of administration are not particularly limited, such as the purpose of prevention (especially prevention of recurrence) and / or clinical treatment, type of disease, patient weight, age, severity of disease, etc. It is selected appropriately according to the conditions.
For example, the following dosage forms can be used, but are not particularly limited.
Gemcitabine: 100 to 1500 mg / m ² , preferably 300 to 1400 mg / m ² , 500 to 1300 mg / m ² is administered by intravenous infusion over 10 to 60 minutes, once a week for 3 consecutive weeks, 4 weeks The drug will be withdrawn, or once a week for 2 consecutive weeks, the drug will be withdrawn for the third week. This is repeated as one course. The dose may be reduced according to the patient's condition.
Olanzapine: 5 to 60 mg, preferably 6 to 50 mg, more preferably 7 to 40 mg, and most preferably 8 to 15 mg are administered once a day or several times a day (morning, noon, evening). In addition, daily administration is preferred, but it can also be administered once every few days or several times every other week.
Cimetidine: 100 to 3200 mg, preferably 200 to 2500 mg, more preferably 300 to 2000 mg, most preferably 400 to 1800 mg is administered once a day or several times a day (morning, noon, evening). In addition, daily administration is preferred, but it can also be administered once every few days or several times every other week.
Sodium valproate: 100 to 3000 mg, preferably 200 to 2500 mg, more preferably 300 to 2000 mg, most preferably 400 to 1600 mg are administered once a day or several times a day (morning, noon, evening). In addition, daily administration is preferred, but it can also be administered once every few days or several times every other week.
Lithium carbonate: 50 to 1500 mg, preferably 100 to 1300 mg, more preferably 200 to 1000 mg, most preferably 300 to 500 mg is administered once a day or several times a day (morning, noon, evening). In addition, daily administration is preferred, but it can also be administered once every few days or several times every other week.

(Treatment schedule using pancreatic cancer therapeutic agent and pancreatic cancer treatment kit)
The treatment schedule using the pancreatic cancer therapeutic agent and pancreatic cancer treatment kit (particularly, the advanced pancreatic cancer therapeutic agent and the progressive pancreatic cancer treatment kit) of the present invention is generally as follows. It can be changed accordingly.
(1) Outline of treatment schedule A GSK3β inhibitory drug and gemcitabine {Gemzar ^(R) } are administered to a patient who has been diagnosed with pancreatic cancer or advanced pancreatic cancer and desires this treatment method (see: Table 1 below ⁾ ).
(2) Dose and administration method (Reference: Table 2 below)
Gemcitabine {Gemzar ^(R) }: 1000 mg / m ² dose once a week for 3 consecutive weeks and 4 weeks off Olanzapine {Product name: Zyprexa ^(R) }: 1 tablet / up to 2 tablets Can be increased (10mg for 1 tablet)
Cimetidine {Product name: Tagamet ^(R) }: 4 tablets / Morning / Evening 8 tablets can be increased (200mg per tablet)
Sodium valproate {Brand name: Depaken ^(R) }: 4 tablets / Morning / Evening 6 tablets can be increased (200mg per tablet)
Lithium preparation {Product name: Remus ^(R) }: 2 tablets / Morning / Evening 6 tablets can be increased (200mg per tablet)
(3) Treatment evaluation method Examination, neurological findings, hematology, drug blood concentration, and image evaluation are evaluated according to methods generally used in clinical practice.
As is understood in the art, treatment with a cancer therapeutic agent is temporarily stopped if toxicity is observed or according to the convenience of the patient without departing from the scope of the present invention. Can then resume.

EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated in detail, the scope of the present invention is not limited by these Examples.
The following cases have been implemented with the approval of the Kanazawa Medical University Clinical Trial Review Board.

(Clinical case 1)
Case 77-year-old woman Unresectable pancreatic tail cancer (current history)
Diagnosed as unresectable advanced pancreatic cancer (Stage IV) in November 1992 and treated with radiation chemotherapy but became resistant to treatment and changed to Gemzar ^(R). A combination therapy of Gemzar ^(R) and GSK3β inhibitor was started in hope of a method.
(Treatment schedule)
Administration of Gemzar ^(R) and GSK3β inhibitors {Remus ^(R) , Tagamet ^(R) , Depaken ^(R) , Diplexa ^(R) } was started in May 1992. One week later, the blood sample showed a slight increase in Cre (1.19). Later, the combination therapy with Gemzar ^(R) and GSK3β inhibitor was resumed, but the patient was discontinued due to anorexia and general malaise.

(Treatment evaluation)
The treatment evaluation is shown in FIG.
During the combined administration of Gemzar ^(R) and GSK3β inhibitor, the increase in the CA19-9 value, which is a cancer marker, was suppressed. However, the CA19-9 value increased rapidly after the combined administration was discontinued.
That is, it was confirmed that the combination therapy of Gemzar ^(R) and GSK3β inhibitor delayed the progression of advanced pancreatic cancer.

(Clinical case 2)
Case 72-year-old female Advanced pancreatic cancer
(Current medical history) Progressive pancreatic cancer (Stage IV) was diagnosed in November 1992 and changed from TS1 (Tegafur / Gimeracil / Oteracil Potassium) to Gemzar ^(R), but this was PD (Progressive). Hope for the treatment method, Gemzar ^(R) and GSK3β inhibitor {Remus ^(R) , Tagamet ^(R) , Depaken ^(R) , Zyprexa ^(R) } were started.
(Treatment schedule)
In August 1990, an unknown fever was observed, and fever due to combined treatment with Gemzar ^(R) and a GSK3β inhibitor was suspected and stopped. However, fever persisted even after discontinuation, and he was later diagnosed with paraneoplastic syndrome.

(Treatment evaluation)
The treatment evaluation is shown in FIG.
The combined use of Gemzar ^(R) and a GSK3β inhibitor lowered the CA19-9 and Span-1 values, which are cancer markers. However, after the combined administration was discontinued, the CA19-9 value and Span-1 value increased rapidly.
That is, it was confirmed that the combination therapy of Gemzar ^(R) and GSK3β inhibitor not only delays the progression of advanced pancreatic cancer but also can suppress it.

(Clinical case 3)
Case 72-year-old female Advanced pancreatic cancer, diabetes (insulin treatment)
(Current medical history) Diagnosed as advanced pancreatic cancer (Stage IV) in November 1992, changed from Gemzar ^(R) to TS1, but became PD, and hoped for this treatment method with Gemzar ^(R) Combination treatment of GSK3β inhibitors {Tagamet ^(R) , Depaken ^(R) } was started.
(Treatment schedule)
Currently, Gemzar ^(R) and GSK3β inhibitor are being used in combination.

(Treatment evaluation)
Treatment evaluation is shown in FIGS.
With respect to FIG. 3, the combined administration of Gemzar ^(R) and GSK3β inhibitor suppresses the increase in CA125, which is a cancer marker. In addition, we were able to treat pancreatic cancer without exacerbating diabetes, a side effect of olanzapine.
Regarding FIG. 4, SUV max (standardized uptake value: an index for expressing the strength of accumulation of radiopharmaceuticals in tumors and organs by ET and SPECT) rapidly decreased in a short time. Such a rapid decrease in a short time is a result that cannot be easily predicted by those skilled in the art in advanced pancreatic cancer.
Referring to FIG. 5, a CT image 3 months after the start of Gemzar ^(R) and GSK3β inhibitor combination therapy confirmed that the tumor was shrinking.
That is, it was confirmed that the combined therapy of Gemzar ^(R) and GSK3β inhibitor can reduce the tumor of advanced pancreatic cancer.

(General)
From the results of the above clinical examples 1 to 3, it was confirmed that the combined administration treatment of Gemzar ^(R) and a GSK3β inhibitor not only delays and suppresses the progression of advanced pancreatic cancer but also can reduce the tumor. Furthermore, it did not worsen diabetes in patients with advanced pancreatic cancer associated with diabetes.

  The present invention can provide a novel therapeutic agent for pancreatic cancer and a kit for treating pancreatic cancer.

Claims (9)

A pancreatic cancer therapeutic agent that combines gemcitabine as an active ingredient, cimetidine as an active ingredient, and sodium valproate as an active ingredient ,
A therapeutic agent for pancreatic cancer, characterized by not combining lithium carbonate .
The pancreatic cancer therapeutic agent according to claim 1, wherein the pancreatic cancer therapeutic agent is a progressive pancreatic cancer therapeutic agent.
The therapeutic agent for pancreatic cancer according to claim 1 or 2, which is the following dosage form:
(1) Gemcitabine: 100 to 1500 mg / m ² once a week for 3 consecutive weeks, 4 weeks off, or once a week for 2 consecutive weeks, 3 weeks off
(2) Cimetidine: 100 to 3200 mg divided into two doses per day, administered daily, administered once every few days, or administered every other week,
(3) Sodium valproate: 100 to 3000 mg divided into two times a day, administered daily, once a few days or several times every other week.
Furthermore, the olanzapine which is an active ingredient is combined, The pancreatic cancer therapeutic agent of any one of Claims 1-3 characterized by the above-mentioned.
5. The therapeutic agent for pancreatic cancer according to claim 4, which is a dosage form in which 5 to 60 mg of olanzapine is administered every day, once every few days, or several times every other week.
The therapeutic agent for pancreatic cancer according to any one of claims 1 to 5, wherein the progressive pancreatic cancer is diabetic progressive pancreatic cancer.
A kit for treating pancreatic cancer comprising gemcitabine as an active ingredient, cimetidine as an active ingredient, and sodium valproate as an active ingredient ,
A pancreatic cancer treatment kit characterized by not containing lithium carbonate .
The kit for treating pancreatic cancer according to claim 7, wherein the kit for treating pancreatic cancer is a kit for treating advanced pancreatic cancer.
  The kit for treating pancreatic cancer according to claim 7 or 8, further comprising olanzapine as an active ingredient.