RU2706339C1 - Method of treating operable pancreatic head adenocarcinoma - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine and aims at treating operable pancreatic adenocarcinoma (AP). Method involves intra-arterial infusion introduction of 50 mg/m² oxaliplatin through catheter into gastroduodenal artery for 20 minutes, then bolus suspension 50 mg/m² Abraxane in no more than 5 ml of Lipiodol, after which the catheter is reinserted into the celiac and intra-arterially infusion 1,000 mg/m² gemcitabine for one hour, followed by surgical removal of tumor, after which no earlier than 2 weeks later, infusion gemcitabine is introduced into a celiac stem in amount of 1,000 mg/m² followed by systemic chemotherapy by oral administration of capecitabine daily at 2,500 mg/m² per day in 2 divided doses in the morning and in the evening for no more than 14 days, not more often 1 time a month before occurrence of undesirable phenomena of II-III degree or progression of tumor process by criteria RECIST.

EFFECT: method provides higher therapeutic tolerance.

1 cl, 1 ex

Description

The invention relates to medicine, more specifically to oncology, and may find application in the treatment of operable 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, prostate cancer is more often observed in people over 40 years old, 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 prostate cancer. 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) FOLFIRINOX (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), but the scheme is very toxic and it is difficult to start with 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 prostate cancer, 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 chemoembolization and chemo-infusion, developed and used in the Federal State Budget Scientific Center of the Russian Science and Technology Center 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 intra-arterial (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, while high expectations from the use of 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.

In addition to chemotherapy, it is known that an additional antitumor effect is achieved by adding radiation therapy to the treatment regimen. It has an additional detrimental effect on tumor cells. It should be noted that the role of radiation therapy in ALA stably takes the place of the palliative method, the main focus of which is the reduction of pain symptoms of the disease. The modern techniques used for three-dimensional conformal planning of radiation projections make it possible to very accurately influence the tumor, leaving healthy tissue practically unaffected, which dramatically reduces the side effects of radiation. Conducted courses of radiation therapy, providing for additional crushing into 2 fractions of the daily dose (multifractionation), can achieve effects on tumor cells located in different phases of the cell cycle, thereby more effectively achieve the desired effect.

Unfortunately, there is a group of patients to whom radiation therapy is contraindicated due to their low general status, due to the course of the underlying disease and a high risk of complications.

The present invention relates to the treatment of such a group of patients.

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 braxan 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 is to optimize the treatment of operable ARF due to the use of oxaliplatin and capecitabine along with abraxan and gemcitabine in the treatment regimen, as well as the sequence path for 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 that oxaliplatin is additionally used as chemotherapy, which is introduced through a catheter installed in the gastroduodenal artery, infusion in an amount of 50 mg / m ² in for 20 minutes, then a bolus of 50 mg / m ² Abraxane slurry was not more than 5 ml of Lipiodol, performing selective embolization of tumor, after which the catheter is repositioned celiac trunk and gemcitabine administered by infusion in an amount of 1000 mg / m ² for one hour, then no earlier than the day after the end of chemotherapy performed surgical removal of the tumor, after which no earlier than two weeks in the celiac trunk administered infusion of gemcitabine at 1000 mg / m ² , dissolved in 100 ml of sodium chloride, for at least 1 hour, then no later than 4 weeks perform systemic adjuvant chemotherapy by oral administration of capecitabine daily 2500 mg / m ² per day in 2 doses in the morning and evening no more e 14 days and intravenous administration of gemcitabine at a dose of 1000 mg / m ² on days 1, 8 and 15, by administering such drugs for no more than 4 months or until adverse events of the II-III degree or progression of the tumor process according to RECIST criteria are observed.

Our use of oxaliplatin is known in the treatment of APA, 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. The 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. 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 with subsequent adjuvant chemotherapy by intraarterial (he / v a valine) infusion Annals of Surgical Hepatology, 2017, No. 2, pp. 54-59).

We also tried to introduce oxaliplatin in our chemotherapeutic treatment regimen for inoperable adenocarcinoma 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 inoperable patients, contributes to an even greater antitumor effect.

Surgical removal of the tumor no earlier than a day after the end of chemotherapy provides optimal conditions for the surgical operation, namely the prevention of adhesions and fibrotic tissue changes in the area of surgical intervention.

And subsequent adjuvant chemotherapy by oral administration of capecitabine monthly for no more than 14 days and intravenous administration of gemcitabine at a dose of 1000 mg / m ² on days 1, 8 and 15 with the implementation of such administration of these drugs for no more than 4 months and / or until the occurrence of adverse events II-III degree and / or progression of the tumor process according to the RECIST criteria, consolidates the obtained positive effect.

The proposed method for the treatment of operable pancreatic adenocarcinoma, which was developed and tested by us under clinical conditions, allowed us to improve the long-term results of treating patients with operable pancreatic artery disease, in the form of an increase in the disease-free period and overall survival of patients.

The essence of the method is illustrated by examples.

Example 1

Patient P., 57 years old. May 13, 2019. He entered the clinic of the Federal State Budgetary Scientific Center of the Russian Scientific Center for Chemical Medicine of the Ministry of Health of the Russian Federation. Academician A.M. Granova with a diagnosis of Pancreatic adenocarcinoma T2-3N0M0, stage IIA.

From the anamnesis it is known:

Since March 2019 there have been complaints of pain in the right hypochondrium, fever up to 38.5 ° C, icteric skin, noted a sharp loss in body weight. I turned for help to the clinic at the place of residence. According to instrumental examinations, an ultrasound scan (ultrasound) of OBP from 04.2019 revealed signs of cholelithiasis (cholelithiasis), cholangitis. Hospitalized in a surgical hospital in an emergency. According to computed tomography (CT) scan of the abdominal organs with intravenous contrast, signs of biliary hypertension, constriction of the common bile duct at the level of the head of the pancreas (pancreas), choledochectasia, and head formation of the pancreas — the area of hypoperfusion in the posterior pancreas, measuring 9 * 9.5 * 10 mm, was revealed.

The histological conclusion of 04.2019: moderately differentiated adenocarcinoma.

Complications: obstructive jaundice from 04.2019. Operation from 04.17.19 g - Cholecystectomy. Drainage of the common bile duct according to Pikovsky. 04/18/19 - migration of drainage according to Pikovsky to the abdominal cavity. Operation 04/18/19 - Drainage of the common bile duct by Keru. Cholangiogenic liver abscesses. Biliary sepsis from 04.2019. Chronic recurrent cholangitis, without exacerbation;

Related: Hypertension 3 tbsp; Arterial hypertension 2 tbsp .; Cardiac ischemia. Atherosclerotic and post-infarction cardiosclerosis (coronary angioplasty, stenting 01.19); Heart failure 2 functional class. Peptic ulcer. Duodenal ulcer.

04/10/2019. Endoscopic retrograde cholangiopancreatography (ERCP) was performed: cholelithiasis, choledocholithiasis. 04/17/2019, surgical treatment was performed in the amount of: laparoscopic cholecystectomy, drainage of the common bile duct according to Pikovsky, biopsy from the area of bile duct stricture. The histological conclusion of 04/03/2019 was adenocarcinoma cells.

04/18/2019, the migration of drainage along the Pikovsky in the abdominal cavity. Repeated surgery was performed in the amount of: laparoscopic diagnosis, abdominal sanitation, drainage of the common bile duct according to Keru.

Oncomarkers from 04/17/2019, CA 19-9 - 2.8 IU / ml, CEA - 2.5 ng / ml. Directed for consultation at the Russian Science and Technology Center named after ak. A.M. Granova for further examination and possible treatment.

On admission 13.05.2019, the patient complains of pain in the right hypochondrium. Weight 75 kg, height 164 cm, body mass index (BMI) - 27.89. body surface area (PPT) - 1.82 m ² .

The condition is satisfactory, conscious, contactable, adequate, oriented in place and time, active. The skin of normal color, clean. Subcutaneous fatty tissue is moderate. The heart rate of 76 beats per minute, the pulse is rhythmic, satisfactory performance. Blood pressure 112/69 mm Hg Hard breathing, carried out in all departments of the lungs, no wheezing. The tongue is wet, clean. The abdomen is not swollen, soft, symmetrical, participates in breathing by all departments, peristalsis is heard clearly, with palpation it is moderately painful in the right hypochondrium. There are no symptoms of peritoneal irritation. Physiological administration unchanged.

The patient was hospitalized for combined treatment in the amount of neoadjuvant chemotherapy and intraarterial chemoembolization of the pancreatic head with subsequent surgical intervention.

The results of the examination before the procedure: Clinical blood analysis dated 05/14/2019: Hemoglobin 141 g / l, red blood cells 4.71 × 10 ¹² / l, platelets 168 × 10 ⁹ / l, white blood cells 5.86 × 10 ⁹ / l, neutrophils 45.5%, Lymphocytes 42.2%, Monocytes 7%, Eosinophils 2.9%, Basophils 0.5%.

Biochemical analysis of blood from 05/14/2019: glucose 4.73 mmol / L, total protein 67 g / L, total bilirubin 16.6 μmol / L, ALT 62 U / L, ACT 36 U / L, amylase 83 U / L.

05/17/2019 - Angiography. Upper mesentericography. Celiacography. Chemoembolization of a pancreatic head tumor with a catheter in the common hepatic.

Under angiooperative conditions, under local anesthesia with 20 ml of a 1% lidocaine solution, a puncture of the left femoral artery was performed according to Seldinger. The Hook 5F catheter is sequentially installed in the superior mesenteric artery, celiac trunk, and common hepatic artery. On angiograms, the vascular anatomy of the hepatopancreatobiliary zone is typical, there are no narrowing or narrowing of the arteries. The expressed stenosis of the celiac trunk was determined. In the projection of the head of the pancreas, the pathological formation of mixed vascularization, blood supply from the branches of the gastroduodenal artery and a diameter of up to 20 mm. In the projection of the liver, distinct pathological formations and neovascularization sites were not visualized. The portal vein trunk and splenic veins are passable throughout. Hepatopetal blood flow. Marked deformation of the contour of the trunk of the superior mesenteric vein, without signs of its deformation.

Conclusion: the angiographic picture corresponded to a malignant neoplasm of the pancreatic head, without signs of vascular invasion. After diagnostic angiography dated 05/17/2019, they started the procedure of intra-arterial chemoinfusion, intra-arterial chemoembolization of the pancreatic head. The first stage was performed by intra-arterial chemoinfusion of an aqueous solution of 91 mg (50 mg / m ² ) of oxaliplatin in the gastroduodenal artery with compression of the blood flow through the gastrointestinal artery. To prepare the solution, a glucose solution of 5% - 50 ml was used, which was mixed with oxaliplatin lyophilisate immediately before administration. The oxaliplatin solution was infused into the gastroduodenal artery for 20 minutes. Immediately after the end of the intra-arterial infusion with oxaliplatin, intra-arterial chemoembolization of the tumor with a suspension consisting of a solution of 91 mg (50 mg / m ² ) of abraxan and 3.0 ml of 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, and nausea. The procedure was transferred without features. Immediately after completion of pancreatic tumor embolization, the catheter was reinserted into the celiac trunk for subsequent intra-arterial chemoinfusion of 1820 mg (1000 mg / m ² ) of gemcitabine, which was prepared by dissolving it in 100 ml of physiological solution immediately before administration. After completion of the intra-arterial chemo-infusion, the arterial catheter was removed.

A pressure bandage was applied to the area of the puncture of the femoral artery.

The patient was immobilized for 8 hours after the removal of the arterial catheter.

Chemotherapy was carried out against the background of supporting conservative therapy: infusion, antiemetic, antisecretory, symptomatic, hepatotropic, antispasmodic. The treatment was transferred without features.

The results of the examination after the procedure: Clinical blood analysis dated 05/18/2019: Hemoglobin 147 g / l, red blood cells 4.71 × 10 ¹² / l, platelets 187 × 10 ⁹ / l, white blood cells 12.95 × 10 ⁹ / l, Neutrophils 85%, Lymphocytes 8.7%, Monocytes 6.3%, Eosinophils 2.9%, Basophils 0%.

Biochemical analysis of blood from 05/18/2019: glucose 8.92 mmol / L, total protein 67 g / L, total bilirubin 26.3 μmol / L, ALT 71 U / L, ACT 53 U / L, amylase 472 U / l

05/20/2019, surgical treatment in the amount of: laparotomy, separation of adhesions, pyloric preserving pancreatoduodenal resection, lymph node dissection, drainage of the abdominal cavity, installation of a nasojunal probe for nutrition.

Histological examination from 05.24.2019 - Moderately low-differentiated ductal pancreatic adenocarcinoma with a pronounced desmoplastic component, perineural invasion and invasion of adipose tissue. Purulent abscessed pancreatitis. The wall of the small intestine, lymph nodes without tumor elements.

The postoperative period was uneventful.

06/03/2019 - performed angiography with catheterization of the celiac trunk for intra-arterial chemoinfusion. Gemcitabine in an amount of 1820 mg, dissolved in 100 ml of sodium chloride, was administered 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. 06/07/2019 the patient was discharged in satisfactory condition for outpatient treatment.

Examination results: Clinical blood test from 07/01/2019: Hemoglobin 109 g / l, Red blood cells 3.62 × 10 ¹² / l, Platelets 299 × 10 ⁹ / l, White blood cells 5.49 × 10 ⁹ / l, Neutrophils 72, 9%, Lymphocytes 14.8%, Monocytes 9.5%, Eosinophils 2.6%, Basophils 0.2%.

Biochemical analysis of blood from 07/01/2019: glucose 5.91 mmol / L, total protein 51 g / L, total bilirubin 9.6 μmol / L, ALT 84 U / L, ACT 82 U / L, amylase 3 U / l

From July 1, 2019, the patient started systemic adjuvant chemotherapy by oral administration of 4550 mg (2500 mg / m ² ) capecitabine per day in 2 doses (in the morning - 2500 mg / m ² and in the evening - 2050 mg / m ² ).

At the same time, the patient was administered three times intravenously 1820 mg (1000 mg / m ² ) of hemicitabine 07/01/2019, 07/08/2019, 07/15/2019. The treatment was tolerated without features.

07/16/2019 - according to the results of the follow-up examination: Oncomarker: CA 19-9 <2 IU / ml, CEA - 1.2 ng / ml.

According to the results of the control examination of the patient, data for relapse of the disease was not received. The continuation of systemic adjuvant chemotherapy in the same mode with the passage of a monthly follow-up examination is recommended.

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

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, as a rule, by an early recurrence of the disease. To reduce the risk of early relapse of the disease associated with micrometastasis, dissemination of tumor cells at the time of surgery, is supplemented by perioperative chemotherapy. However, in most cases, a full-fledged systemic chemotherapy is limited by the low general status of patients and is associated with high risks of subsequent surgical treatment.

Our regional neoadjuvant and adjuvant chemotherapy combined with neoadjuvant intra-arterial chemoembolization in gentle modes allowed us to achieve good tolerability of the claimed combined treatment while maintaining a significant antitumor effect, which is manifested by the absence of signs of disease recurrence in the patient and a satisfactory quality of life.

By July 2019, the proposed method treated 3 patients with the achievement of stabilization of the underlying disease.

The proposed method for treating operable adenocarcinoma of the pancreatic head is new and tested by us under clinical conditions, and therefore we do not have long-term follow-up results, but the positive results of such treatment obtained with a satisfactory condition of the patients allow us to hope that the achieved result will be preserved in the future.

The method is developed in the Department of Operative Surgery No. 2 of the Academician Granov A.M. and underwent clinical testing in 3 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, then surgical removal of the tumor is performed not earlier than one day after the end of chemotherapy, after which infusion of gemcitabine in an amount of 1000 mg / m ² is introduced not earlier than 2 weeks later. dissolved in 100 mL of sodium chloride, for at least 1 hour, then no later than 4 weeks of systemic adjuvant chemotherapy is performed by oral administration of capecitabine daily 2500 mg / m ² per day in 2 divided doses, morning and evening not more than 14 days and intravenously Nogo administration of gemcitabine 1000 mg / m ² to 1, 8 and 15 hours, carrying out such administration of these drugs is not more than 4 months, or until adverse events II-III extent or progression of tumor by RECIST criteria.