RU2706347C1 - Method of treating operable pancreatic head adenocarcinoma - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to a method of treating operable pancreatic head adenocarcinoma. Method of treating operable pancreatic adenocarcinoma, including intra-arterial administration of chemotherapeutic agents Abraxane and gemcitabine, wherein the chemopreparations are additionally oxaliplatin, which is introduced through a catheter inserted into a gastroduodenal artery, infusion, then bolus Abraxane, performing selective tumor embolization, after which the catheter is reinserted into the celiac and the gemcitabine is infused, not earlier than one day after the chemotherapy, sessions of the conformal radiation therapy are performed; surgical removal of the tumor is performed not earlier than the day after the end of the radiation therapy, after which no earlier than 2 weeks later infusion of gemcitabine is introduced into a cogwheel, then no later than 4 weeks, systemic adjuvant chemotherapy is performed by oral administration of capecitabine and simultaneous intravenous administration of gemcitabine, implementing such administration of these preparations for not more than 4 months or until occurrence of undesired phenomena of II-III degree or progression of tumor process according to RECIST criteria, taken in certain proportions and under certain conditions.

EFFECT: method described above provides improved clinical results in patients with operable pancreatic head adenocarcinoma in the form of an increase in the recurrence-free period and overall survival of the patients.

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Description

The invention relates to medicine, more specifically to oncology, and may find application in the treatment of pancreatic adenocarcinoma (AP).

Adenocarcinoma is one of the types of pancreatic cancer (PCa) and the most aggressive malignant neoplasm with a negative statistical prognosis for both sexes around the world.

According to statistics from the World Health Organization, in 2018, more than 430,000 cases of prostate cancer were recorded worldwide. It occupies 12th place in the structure of mortality from cancer in men and 11th place in women. According to the forecasts of the American Cancer Society, mortality from prostate cancer worldwide is 4.4%, and by 2020 it is projected to take 2nd place in mortality from cancer [American Cancer Society.Facts & Figures 2018].

In the Russian Federation in 2017, 16,188 new cases of prostate cancer were recorded, of which only 17.7% had an operable stage of the disease (Art. I-II). In the structure of oncological morbidity in the Russian Federation, prostate cancer is 3.1%. It has the highest mortality rate among all malignant tumors and is the fourth most common cause of death from malignant

tumors in the adult population.

According to global statistical studies, AJ is more often observed in people older than 40 years, the peak incidence comes from 45-80 years. Late diagnosis of prostate cancer is due to the absence of specific symptoms in the early stages and proceeds under the guise of other diseases of the upper gastrointestinal tract.

Malignant tumors of the gastropancreatoduodenal region, which include APA, are characterized by early lymphogenous metastasis and damage to regional lymph nodes is an unfavorable factor. At the time of diagnosis, more than 70% of patients have an inoperable or locally advanced stage of the disease.

To date, the most significant results in the treatment of APA can only be achieved with radical surgical interventions. However, surgical treatment is possible only in 20% of patients with a pancreatic tumor, of which only a few subsequently receive adequate adjuvant chemotherapy (AHT) [Cancer 1996; 78 (3): 664-673].

The unsatisfactory results of surgical operations have clearly shown the insufficiency of only surgical treatment of patients with AP. Comprehensive treatment of this category of patients using arterial chemotherapy (AXT) has better results compared to exclusively surgical treatment. The combination of AChT and surgical intervention can increase the life expectancy of patients by an average of 20 months. However, the use of chemotherapy is often accompanied by phenomena of systemic toxicity: nausea, vomiting, weight loss, diarrhea, neutropenia and, as a rule, is delayed due to the severity of the patients' condition in the postoperative period and the low adherence of patients to this type of treatment [Oncology 2001; 60 (1): 8-18].

Chemotherapy is carried out depending on the somatic state and the sensitivity of the tumor to chemotherapy drugs. According to the expected effect, they are divided into lines:

- chemotherapy regimen (treatment before progression / unacceptable toxicity) FOLFIRTNOX (oxaliplatin 85 mg / m ² intravenously (iv) 120 min., irinotecan 180 mg / m ² iv 90 minutes, calcium folinate 400 mg / m ² / in 120 min., 5-fluorouracil 400 mg / m ² iv bolus, 5-fluorouracil 2400 mg / m ² iv infusion for 46 hours, every 2 weeks). However, this treatment regimen is very toxic and difficult to perform in somatically severe patients.

- Gemcitabine monotherapy, which has a very good property: in mono-mode it improves the quality of life and reduces the manifestation of pain and side effects of the tumor, but slightly affects the formation itself.

- gemcitabine with Abraxan, in / in the introduction - better tolerated and fewer adverse reactions.

- gemcitabine with platinum (preparations containing platinum) - tolerance scheme at the same level as gemcitabine + abraxan.

- the combination of gemcitabine and erlotinib is not recommended for use in AR, because the addition of erlotinib to gemcitabine, according to a randomized study, showed a minimal advantage in longevity with a significant increase in toxicity.

For many years, the main standard chemotherapeutic treatment for both operable and inoperable pancreatic malignancies remained treatment with gemcitabine, which is superior in efficacy to 5-fluorouracil (5-FU) in terms of median overall survival (5.7 months in case of gemcitabine compared to 4 , 2 months in the case of 5-FU), the average duration of disease progression (2.1 months in the case of gemcitabine compared with 0.9 months in the case of 5-FU), as well as in relation to clinically favorable reactions. However, despite the fact that treatment with gemcitabine has become the standard chemotherapy for pancreatic malignancies, since the method was approved in 1996, progress in treatment has been very small. For all cases of pancreatic cancer, combined, the percentage of patients with a relative 5-year survival in the case of prostate cancer between 1996 and 2004 was 5%, i.e. significantly lower than the survival rate for other cancers (American Cancer Society, Surveillance and Health Policy Research (2009).

The most acceptable method of treatment at present is intra-arterial (IV) chemoembolization and chemoinfusion, developed and used in the Federal State Budget Scientific Center of the Russian Scientific Center for Chemical Chemistry named after Acad. Granova A.M., which has long established itself as an effective treatment for prostate cancer. Selective intra-arterial use of drugs is one of the ways to increase the effectiveness of antitumor treatment. Most modern chemotherapeutic agents are not intended for IV use. To date, 5-fluorouracil remains the only cytostatic approved for iv use.

An analysis of domestic and foreign literature on X-ray endovascular studies in the treatment of tumors for the purpose of diagnosis and treatment showed great interest in the lipotropic radiopaque drug Lipiodol UltraFluid (Lipiodol) developed by Guerbet (France).

The interest of researchers is due to the ability of the drug to penetrate and linger for a long time in the tumor tissue when it is introduced into the vessels of the tumors, showing diagnostic effectiveness and, in some cases, antitumor effect.

The main advantage of this method is an improvement in the quality of life of patients, as well as an increase in the effectiveness of the delivery of chemotherapy drugs to the vessels that feed the tumor. The quality of life is improved by delivering the chemotherapy drug to the tumor directly through the vessel that feeds it, which reduces the toxic effect on other tissues and the body as a whole. The effect is achieved due to the "first passage" of the drug and a significant increase in its concentration around the neoplasm (RF Patent No. 2156137).

The method includes regional chemotherapy, in which about 50% of the chemotherapy drug remains in the tumor node, creating a peak concentration in it. Given the small diameter of the pancreatic arteries, the catheter itself, due to its size, causes a slowdown in blood flow, which additionally prolongs the contact time of the chemotherapy with the tumor. A feature of the method is a sharp slowdown in regional blood flow in the tumor by selective embolization of its arteries. Performed embolization is reversible. The injected embolizate is distributed along the microvasculature, followed by diffusion into the tissue. Such a mechanism provides prolonged exposure to a high dose of a chemotherapeutic agent directly in the tumor tissue, thereby providing an increase in the antitumor effect.

The safety of the method was proved in experimental studies, which was then confirmed by the clinical use of the method. Features of the distribution of chemoembolizate make it possible to exert a prolonged selective effect not only on the primary focus, but also on regional lymph and hematogenous micrometastases of the pancreatic tumor.

In recent years, targeted drugs have been actively used for various tumor diseases. EGFR and VEGF inhibitors have shown high efficacy in metastatic colorectal cancer and metastatic kidney cancer, and the high expectations of using targeted drugs in the treatment of pancreatic cancer have not been met. So, Erlotinib remains the only targeted drug that has shown high efficacy in patients with metastatic and locally advanced pancreatic cancer. According to the results of the study, a statistically significant increase in median survival was achieved, which was 6.24 months and 5.91 months in the Erlotinib + Gemcitabine and Gemcitabine groups, respectively, while the frequency of objective responses was not statistically different, while the frequency of adverse events was significantly higher in the group of patients undergoing treatment with a combined regimen.

In separate studies (1996-1998) with pancreatic adenocarcinoma (AP), preparations of the taxane group were used. And yet, standard forms of drugs of this group are not widely used in the treatment of ARA due to high toxicity rates.

The desire to achieve greater effectiveness of the treatment of APA with minimal invasiveness of exposure has led to the emergence of intra-arterial administration of chemotherapy drugs with occlusion of the vessels of the tumor using effective safe radiopaque drugs.

This served as the basis for the development of more advanced low-toxic methods of treating adenocarcinoma in connection with the emergence of new highly effective chemotherapeutic agents.

In recent years, paclitaxel has been widely used to treat neoplasms. The drug is practically insoluble in water, therefore, for clinical use, a special dosage form was developed - taxol, which is a concentrate of paclitaxel, dissolved in a mixture of polyoxyethylated castor oil (Cremophor EL with ethanol). The choice of solvent was forced to a certain extent, since it causes acute hypersensitivity reactions and enhances the toxic effect of paclitaxel. To overcome toxic reactions, a system of preventive measures was developed. When carrying out intravenous infusions of Taxol, the use of special systems of polypropylene or polyolefin was required, because cremophor is able to flush plasticizer from plasticized polyvinyl chloride into the blood, from which standard infusion systems are made. In experimental studies, it was shown that this plasticizer is very toxic, has carcinogenic properties, cardiopulmonary toxicity, hepato and nephrotoxicity. All of the above properties of taxol do not allow its use as a drug for regional (intra-arterial) administration.

To overcome these negative aspects, in 2014 a new form of paclitaxel stabilized by albumin, called Abraxan, was developed.

Abraxan is a conventional, unmodified, paclitaxel in the form of nanoparticles obtained by special processing of a mixture of paclitaxel with human albumin. When diluting the drug with water, a suspension is obtained that is suitable for intravenous administration. The good solubility of abraxan in water can reduce the duration of infusion to 30 minutes instead of 3 hours when treated with taxol. The mechanism of action of abraxan is similar to the action in the form of taxol.

The distinctive properties of the new drug, especially its ability to quickly penetrate through the walls of the capillaries and adsorb into the tissues, and it is tropic to the tissues of the pancreas and liver, make abraxan promising for selective intra-arterial use.

Along with abraxan, gemcitabine is used to treat neoplasms. Gemcitabine monotherapy has long been a standard in the treatment of pancreatic cancer patients. With the development of oncology, multicomponent chemotherapy regimens have been actively used, in which gemcitabine is also successfully used. In the treatment of pancreatic cancer, the best effect in the form of an increase in 5-year survival was achieved with the use of FOLFIRINOX and gemcitabine + abraxan regimens.

A method of treating operable adenocarcinoma with gemcitabine and abraxan, in our opinion, is the closest to the proposed one and we have taken it as a prototype. (Patent application dated 05/20/2011 No. 2012156275/15, USA DISAI Neil P., COOH-SHIONG Patrick).

The patent describes the treatment of a wide variety of nosologies, including patients suffering from pancreatic cancer with a combination of gemcitabine and abraxan by intra-arterial administration, but without a detailed description of the procedure. For the treatment of various nosologies, the dose of abraxan is from 100 to 400 mg / m ² . It is also noted that such administration can be carried out in various ways, for example, intravenously, intraarterially, intraperitoneally, intra pulmonary, oral, inhalation, intravesicular, intramuscularly, intratracheally, subcutaneously and even intraocular, intratracheal, transmucosal and transdermal.

It should be noted that the authors did not give specific examples of the use of such a composition, the treatment of each of the given nosologies with its use, the optimal tactics of managing specific patients is not given, which would require a specific analysis and systematization of the data obtained.

The present invention, in our opinion, is a significant contribution to the treatment of pancreatic neoplasms, including its adenocarcinoma, which, as we said above, is the most aggressive malignant neoplasm with a negative statistical prognosis.

The technical result of the present invention consists in optimizing the treatment of operable pancreatic adenocarcinoma due to the use of oxaliplatin and capecitabine and conformal radiation therapy along with abraxan and gemcitabine in the treatment regimen, as well as the path and sequence of their implementation.

This result is achieved by the fact that in the known method of treating operable ARF, including intra-arterial chemotherapy with abraxan and gemcitabine, according to the invention, oxaliplatin is additionally used as chemotherapeutic agents, which are introduced through a catheter inserted into the gastroduodenal artery, infusion in an amount of 50 mg / m ² into for 20 minutes, then carry out selective embolization of the tumor with a suspension of abraxan in an amount of 50 mg / m ^{2 in} no more than 5 ml of lipiodol, after which the catheter is reinstalled in h a jealous trunk and gemcitabine are infused in an amount of 1000 mg / m ² for one hour, not earlier than a day after the end of chemotherapy, conformal radiation therapy sessions are carried out in multifraction mode daily in fractions of 2 Gy 2 times a day with an interval of at least 6 hours between they, up to a total physical focal dose of 50 Gy, which is equivalent to 60 Gy of conventional fractionation, perform surgical removal of the tumor no earlier than one day after the end of radiation therapy, after which no earlier than 2 weeks later ny barrel administered infusion of gemcitabine at 1000 mg / m ^2, dissolved in 100 ml sodium chloride, for at least 1 hour, then no later than 4 weeks operate adjuvant chemotherapy through oral capecitabine daily 2500 mg / m ² per day in 2 doses morning and evening no more than 14 days and simultaneous intravenous administration of gemcitabine at a dose of 1000 mg / m ² on days 1, 8 and 15, by administering these drugs for no more than 4 months or until the appearance of adverse events of the P-III degree or the progression of the tumor process according to RECIST criteria.

Our use of oxaliplatin is known in the treatment of pancreatic cancer, including in combination with gemcitabine. Their synergistic effect in the culture of tumor cells was studied, and in patients with ARV who received a combination of these drugs, in comparison with gemcitabine monotherapy, they managed to get a greater response. At the same time, despite higher treatment efficacy indicators, a higher toxicity of such a combination was noted in the literature compared with gemcitabine monotherapy, in particular, the predominance of such adverse events as vomiting, thrombocytopenia, and neuropathy was reported. Nevertheless, such a combination was recommended for chemotherapeutic treatment of pancreatic adenocarcinoma (Moiseenko V.E. Rationale for the use of perioperative regional chemotherapy with gemcitabine and oxaliplatin in the combined treatment of ductal adenocarcinoma of the pancreatic head, abstract of Ph.D. Ph.D. named after academician AM Granov ”, S.-Pb, 2018).

The use of oxaliplatin with gemcitabine is also known in combination with surgical intervention as a neoadjuvant regional chemotherapy, while gemcitabine is administered in a suspension of lipiodol in the gastroduodenal artery, supplemented with an infusion of oxaliplatin followed by adjuvant chemotherapy with hepatic hepatitis C and hepatitis C , 2017, No. 2, pp. 54-59).

We tried to introduce oxaliplatin into the scheme of our chemotherapeutic treatment of operable pancreatic adenocarcinoma of the pancreatic head as one of the stages of our proposed method.

Since earlier, in the treatment of pancreatic neoplasms, we used selective intra-arterial use of chemotherapy drugs with subsequent slowdown of blood flow, which is one of the ways to increase the effectiveness of antitumor treatment by delaying the chemotherapy drug in the tumor tissue and thereby prolonging the antitumor effect, we supplemented the infusion of oxaliplatin with selective tumor embolization of the tumor lipiodole, which allowed to enhance the antitumor effect, and subsequent infusion The onset administration of gemcitabine through the same catheter reinstalled in the celiac trunk, as we have shown in the treatment of operable patients, contributes to an even greater antitumor effect. And finally, the implementation after the end of chemotherapy of conformal radiation therapy by multifraction to a total physical focal dose of 50 Gy, which is equivalent to 60 Gy of conventional fractionation, has an almost complete fatal effect on tumor cells. It should be noted that the role of radiation therapy in prostate cancer steadily takes the place of the palliative method, the main focus of which is the reduction of pain symptoms of the disease. We made an attempt to use it as a method of combined treatment simultaneously with the proposed chemotherapy regimen. We note at the same time that the modern methods of three-dimensional conformal planning of radiation projections that we use allow us to very accurately influence the tumor, leaving healthy tissue practically unaffected, which dramatically reduces the side effects of radiation. At the same time, our courses of radiation therapy, which provide for additional crushing into 2 fractions of the daily dose (multifractionation), allow us to achieve effects on tumor cells located in different phases of the cell cycle, thereby more effectively achieve the desired effect. Thus, the combination of the two methods we use (multifractionation of radiation therapy and intra-arterial chemotherapy) significantly improves the positive results of treatment.

Surgical removal of the tumor no earlier than a day after the end of radiation therapy provides optimal conditions for the surgical operation, namely the absence of pronounced postradiation complications in the form of a significant adhesive process and fibrotic tissue changes in the surgical area. At the same time, the positive effects of radiation therapy are manifested in the form of a decrease in the metabolic activity of the tumor, a decrease in the tumor mass, which increases the ablasticity of the surgical treatment.

And subsequent adjuvant chemotherapy by oral administration of capecitabine in an amount of 2500 mg / m ² daily for no more than 14 days and intravenous administration of gemcitabine in an amount of 1000 mg / m ² on days 1, 8 and 15, such administration of these drugs for no more than 4 months or before the appearance of adverse events of the II-III degree or the progression of the tumor process according to the RECIST criteria, fixes the resulting positive effect.

The essence of the method is illustrated by examples.

EXAMPLE 1. Patient M., years. He was admitted to the clinic of the Federal State Budget Scientific Research Center for Science and Technology of the Ministry of Health of the Russian Federation on 01.11.2018 with a diagnosis of Adenocarcinoma of the pancreatic head T3N0M0 II st.

Complications: obstructive jaundice from 08.2018. Percutaneous transhepatic external-internal cholangio-drainage from 08.2018.

From the anamnesis: Considers himself ill since August 2018, when he noted pain in the epigastrium. In connection with the increase in signs of obstructive jaundice, percutaneous transhepatic external-internal cholangio-drainage was performed from 08.2018. According to magnetic resonance imaging (MRI) from 10/15/2018 - a solid solid formation in the head of the pancreas, sizes 48 * 40 * 41 mm.

Oncomarker CA19-9 from 10.19.18 - 1637 U / ml. According to a histological study dated 10/22/2018 - adenocarcinoma.

He was sent for consultation at the Russian Science and Technology Center for additional examination and treatment.

Upon admission to the RSC on November 1, 2018, complaints of moderate pain in the right hypochondrium. Objectively: satisfactory condition, height 182 cm, weight 74 kg, body surface area (PPT) = 1.95 m ² . The skin is clean, the lymph nodes are not enlarged. Borders of the heart within normal limits, heart rate (HR) 76 beats / min, heart sounds are clear, rhythmic. The chest is regular in shape, symmetrically involved in breathing, hard breathing, no wheezing. The abdomen is soft, painless, the liver at the edge of the costal arch, the spleen is not enlarged. The kidneys are not palpable. Physiological administration unchanged.

The patient was hospitalized for intra-arterial chemoembolization of a pancreatic tumor.

The results of the examination before the start of the procedure: Oncomarker CA19-9 o - 1637 U / ml.

Clinical blood analysis dated 02/02/2018: Hemoglobin 139 g / l, red blood cells 4.75 × 10 ¹² / l, platelets 322 × 10 ⁹ / l, white blood cells 6.54 × 10 ⁹ / l, neutrophils 63.2%, lymphocytes 18 %, Monocytes 6.7%, Eosinophils 11.4%, Basophils 0.7%.

Biochemical analysis of blood from 02.11.2018: glucose 4.5 mmol / L, total protein 72 g / L, total bilirubin 24.9 μmol / L, ALT 86 U / L, ACT 35 U / L, amylase 17 U / L.

November 6, 2018 - Diagnostic angiography. Upper mesentericography. Celiacography.

Under angiooperative under local anesthesia with 20 ml of a 1% solution of novocaine, the right femoral artery was punctured according to Seldinger. The Hook 5 F catheter is alternately inserted in the superior mesenteric artery and celiac trunk.

On angiograms, the vascular anatomy of the hepatopancreatobiliary zone is typical. We have visualized usation and local stenosis of the gastroduodenal artery. In the projection of the pancreatic head, a pathological formation with a diameter of up to 3 cm containing tumor vessels was determined. The narrowing of the trunks of the superior mesenteric and splenic veins to 1/3 of the lumen was visualized. The portal vein is passable throughout.

Conclusion: malignant neoplasm of the pancreas.

After diagnostic angiography from 11/06/2018, they started the procedure of intra-arterial chemoinfusion, intra-arterial chemoembolization of a pancreatic head tumor.

The first stage was an intra-arterial infusion of an aqueous solution of 97.5 mg (50 mg / m ² ) of oxaliplatin into the gastroduodenal artery. To prepare the solution, a glucose solution of 5% - 50 ml was used, which was mixed with oxaliplatin lyophilisate immediately before administration. Oxaliplatin solution was infused into the gastroduodenal artery for 20 minutes.

Immediately after the end of the intra-arterial infusion of oxaliplatin, intra-arterial chemoembolization of the tumor with a suspension consisting of a solution of 97.5 mg (50 mg / m ² ) of abraxan and 5 ml of oil-soluble radiopaque lipiodol was performed.

The suspension was prepared immediately before the embolization procedure. Abraxan lyophilisate was dissolved in 10 ml of physiological saline and emulsified in lipiodol.

During the embolization procedure, the patient noted severity, moderate epigastric pain, a feeling of “warmth” in the abdominal cavity, nausea, and vomiting once. The procedure was transferred without features. Immediately after completion of pancreatic tumor embolization, the catheter was reinstalled in the celiac trunk for subsequent intraarterial chemoinfusion of the gemcitabine preparation.

On November 6, 2018, 30 minutes after the administration of the chemoembolizate, intraarterial chemoinfusion was started with an aqueous solution of 1950 mg (1000 mg / m ² ) of gemcitabine. Its solution was prepared immediately before administration, dissolving gemcitabine in 100 ml of physiological saline. After completion of intra-arterial chemoinfusion, the arterial catheter was removed, a pressure bandage was applied to the area of the femoral artery puncture. The patient was immobilized for 8 hours after the removal of the arterial catheter. The treatment was transferred without features.

Clinical blood test dated 11/12/2018: Hemoglobin 140 g / l, red blood cells 4.66 × 10 ¹² / l, platelets 259 × 10 ⁹ / l, white blood cells 7.96 × 10 ⁹ / l, neutrophils 53.3%, lymphocytes 32 , 5%, Monocytes 12.4%, Eosinophils 2.4%, Basophils 0.4%.

Biochemical analysis of blood from 11/12/2018: glucose 6.03 mmol / L, total protein 70 g / L, total bilirubin 23.8 μmol / L, ALT 97 U / L, ACT 28 U / L, amylase 12 U / L.

In the period from November 12, 2018 to November 30, 2018, a course of neoadjuvant conformal radiation therapy was carried out in multifraction mode daily in fractions of 2 Gy 2 times a day with an interval of at least 6 hours between them to a total physical focal dose of 50 Gy, which is equivalent to 60 Gy of conventional fractionation . Radiation therapy was carried out against the background of supporting conservative therapy: infusion, antiemetic, antisecretory, symptomatic. The treatment was transferred without features.

12/03/2018 Operation. Laparotomy Split splice. Pyloric preserving pancreatoduodenal resection. Lymphatic dissection. Resection of the portal vein. Cholecystectomy Abdominal drainage. Installation of a nasoyunal probe.

Histological examination from 10.12.2018:

1) Vein wall with growths in adventitia and the middle membrane of ductal adenocarcinoma;

2) The surgical edge of the resection without tumor elements;

3) Ductal adenocarcinoma of the pancreas without invasion into the wall of the duodenum 12, with perineural invasion and ingrowth into adipose tissue, with signs of therapeutic pathomorphism of Art.

Conservative therapy, infusion, symptomatic, antisecretory antibacterial, hepatotropic, replacement therapy was carried out.

The postoperative period without features.

12/17/2018 - performed angiography with catheterization of the celiac trunk for intra-arterial chemoinfusion. Gemcitabine in an amount of 1950 mg, dissolved in 100 ml of sodium chloride, was injected intraarterially through a catheter inserted into the celiac trunk for at least 1 hour. The patient underwent treatment without features. Adverse events of chemotherapy were not identified. 12/21/2018 the patient was discharged in satisfactory condition for outpatient treatment.

From January 14, 2019, the patient was given an adjuvant chemotherapy course by oral administration of 4875 mg (2500 mg / m ² ) capecitabine per day in 2 doses (2800 mg in the morning and 2075 mg in the evening) for 14 days until January 28, 2019 At the same time, 1950 mg (1000 mg / m ² ) of hemicitabine was administered three times intravenously to the patient on January 14, 2019, January 21, 2019, and January 28, 2019 (1, 8, and 15 days).

From 02/12/2019 to 02/25/2019 - a similar course of adjuvant chemotherapy was performed on an outpatient basis. The patient's condition is satisfactory.

From March 12, 2019 to March 25, 2019 - a similar course of adjuvant chemotherapy on an outpatient basis was carried out. The patient's condition remained satisfactory.

From 04/09/2019 to 04/22/2019 - a similar course of adjuvant chemotherapy on an outpatient basis was carried out. The patient's condition is satisfactory.

The treatment was tolerated without features. Only non-hematologic adverse events of the chemotherapy degree that did not require inpatient treatment were noted.

04/25/2019 - according to the results of the control examination: Oncomarker CA19-9 - 87 units / ml. According to computed tomography of the chest, abdominal cavity, pelvis with intravenous contrasting, no data were obtained for relapse of the disease. Recommended routine follow-up with an oncologist at the place of residence.

Conclusion: a patient with an operable adenocarcinoma of the pancreatic head.

The patient is still in remission.

The treatment standard for this group of patients is only surgical treatment, not involving perioperative chemotherapy. Despite the good direct indicators of surgical treatment, long-term results remain extremely disappointing, which is manifested by an early relapse of the disease.

In most cases, a full-fledged systemic polychemotherapy with a limited low general status of patients and high risks of subsequent surgical treatment. On the other hand, conducting systemic chemotherapy in a reduced mode seems to be ineffective.

Our regional perioperative polychemotherapy combined with intra-arterial chemoembolization and preoperative radiation therapy allowed us to achieve satisfactory treatment tolerance in the absence of signs of disease relapse according to computed tomography, a persistent decrease in the CA19-9 tumor marker and a satisfactory quality of life for the patient who is currently in remission during remission 9 months.

By July 2019, the proposed method treated 7 patients with the achievement of stabilization of the underlying disease for 6 to 11 months, which distinguishes our method from the known ones.

The proposed method for the treatment of operable pancreatic adenocarcinoma of the pancreatic head, developed and tested by us under clinical conditions, has allowed us to achieve improved treatment outcomes for patients with operable APA in the form of an increase in the relapse-free period and overall survival of patients.

The method is developed in the Department of Operative Surgery No. 2 of the Academician Granov A.M. and underwent clinical testing in 7 patients with a positive result.

Claims (1)

A method of treating operable pancreatic adenocarcinoma, including intra-arterial administration of chemotherapy drugs abraksan and gemcitabine, characterized in that oxaliplatin is additionally used as chemotherapy drugs, which is introduced through a catheter installed in the gastroduodenal artery, infused in an amount of 50 mg / m ² for 20 minutes, then bolus 50 mg / m ^{2 of} abraxan in suspension in not more than 5 ml of lipiodol, performing selective tumor embolization, after which the catheter is reinstalled in the celiac trunk and mcitabine is infused in an amount of 1000 mg / m ² for one hour, not earlier than a day after the end of chemotherapy, conformal radiation therapy sessions are carried out in multifraction mode daily in fractions of 2 Gy 2 times a day with an interval of at least 6 hours between them to the total physical focal dose of 50 Gy, which is equivalent to 60 Gy of conventional fractionation, surgical removal of the tumor is performed not earlier than one day after the end of radiation therapy, after which no earlier than 2 weeks are injected into the celiac trunk infusion of gemcitabine in an amount of 1000 mg / m ² dissolved in 100 ml of sodium chloride for at least 1 hour, then systemic adjuvant chemotherapy is performed no later than 4 weeks by oral administration of capecitabine daily 2500 mg / m ² per day in 2 doses in the morning and in the evening no more than 14 days and simultaneous intravenous administration of gemcitabine in the amount of 1000 mg / m ² on days 1.8 and 15, by administering these drugs for no more than 4 months or until adverse events of the II-III degree or progression of the tumor process to RECIST criteria.