Start of section
Production, amateur
Radio amateurs
Aircraft model, rocket-model
Useful, entertaining 		Stealth Master
Electronics
Physics
Technologies
Inventions 		Secrets of the cosmos
Secrets of the Earth
Secrets of the Ocean
Tricks
Map of section
Start
Forum
Use of the site materials is allowed subject to the link (for websites - hyperlinks)

Navigation: =>

Home / Patent catalog / Catalog section / Back /

ONCOLOGY AND RADIOLOGY
INVENTION
Patent of the Russian Federation RU2283107

METHOD FOR TREATMENT OF EXPANDED OVARIAN CANCER

The name of the inventor: Sidorenko Yuri Sergeevich (RU); Verenikina Ekaterina Vladimirovna (RU); Francetz Elena Mihailovna (RU); Nero Galina Andreevna (RU)
The name of the patent holder: Rostov Research Oncological Institute of the Ministry of Health of the Russian Federation (RU); Sidorenko Yuri Sergeevich (RU); Verenikina Ekaterina Vladimirovna (RU); Francetz Elena Mihailovna (RU); Nero Galina Andreevna (RU)
Address for correspondence: 344037, Rostov-on-Don, line 14, 63, Rostov Research Oncological Institute of the Ministry of Health of the Russian Federation
Date of commencement of the patent: 2005.02.15

The invention relates to medicine, in particular to oncology, and can be used to treat patients with advanced ovarian cancer. To do this, at the first stage, surgery is carried out with the removal of micro-irrigators through the posterior fornix; after two weeks, chemotherapy begins: on the first day, cyclophosphamide 1000 mg / m 2 and carboplatin 150 mg / m 2 on autoplasmochemotherapy with a plasma deprived of cellular elements, and Lymphocytes isolated from blood plasma are incubated with 1.2 mg of proleukin for 24 hours and administered on the second day into the abdominal cavity through a micro irrigator. This sequence of procedures is repeated every 3 weeks 4 courses, then every 6 weeks - 6 courses. The method allows to reduce the side toxic effects of antitumor therapy due to the immunostimulating effect associated with the activation of cytotoxic subpopulations of lymphocytes, and the reduction of its time.

DESCRIPTION OF THE INVENTION

The invention relates to medicine, namely to oncology, and can be used to treat patients with malignant process of the uterine appendages.

In the treatment of ovarian cancer, it is very important to choose the first phase of combined treatment. As for patients with advanced ovarian cancer, the choice of the first stage is controversial: if some authors always suggest starting with surgery, many others prescribe chemotherapy for operative intervention in order to reduce the volume of tumor masses and pathological effusions.

A comparative method of treatment of advanced ovarian cancer is known (Ya.V. Bokhman "Oncogynecology Guide", L .: Medicine, 1989). The effectiveness of the treatment was evaluated according to the survival criteria and the fact of the onset and duration of objective remission, obtained as a whole from the two treatment options analyzed, 413 patients with ovarian cancer: surgery + chemotherapy and chemotherapy plus surgery, and within these options. Statistical processing used a dynamic method. The results of the study revealed that, according to the criterion of survival of patients with advanced ovarian cancer, the option "surgery + chemotherapy" turned out to be the most profitable. Objective remission was observed in both treatment options, mainly after the first stage, regardless of the method by which the stage was presented, with almost the same frequency of 88.5% and 85.8% and was further supplemented by remission after the second stage of each variant Treatment. At the same time, the duration of remission obtained with chemotherapy as the first stage of treatment was shorter than the duration of remission after surgery. The results of a prospective randomized study on the criterion of the duration of remission confirmed that the treatment option "surgery + chemotherapy" is more effective. A further evaluation showed that in some clinical situations (with combination of ascites and hydrothorax, and in cases where the mass of metastases prevailed over the mass of the primary tumor), the duration of remission after surgery and after chemotherapy as the first stages of treatment was almost identical.

However, the duration of remission in the majority of patients did not exceed 9 months, and the 3-year survival rate ranged from 18-35%.

Known is a method for the treatment of advanced ovarian cancer (Nechunaeva TT, Blumberg AG, Lazarev AF Optimization of treatment for advanced ovarian cancer // In: Current state and prospects of development of experimental and clinical oncology Materials of the Russian scientific-practical conference, Devoted to the 25th anniversary of the Oncology Research Institute of the Tomsk State Medical University, Tomsk, June 24-25, 2004). In the treatment of progressive ovarian cancer in the adjuvant variant, two combinations of chemotherapeutic agents were used, with an interval between courses of 2-3 weeks: hexalene 160 mg / m 2 / per os / day 1-14 days + gemzar 800 mg / m 2 1, 8, 15 Days in / in the drip or hexalene 160 mg / m / per os / day 1-14 days + Vepesid 50-60 mg / m 2 / per os / day 1-14 days. According to the first scheme, 28 courses of treatment were conducted, the second - 32. Evaluation of the results was conducted after each course.

However, the effectiveness of the applied combinations was only 43% (complete remissions - 2 people), stabilization of the process was noted in 29% of cases and progression - in 28% of cases. Hematological toxicity was manifested by leukopenia up to 1.7 × 10 9 , anemia - up to 80 g / l. The median survival in the group was 10.2 months.

Known is a method for the treatment of ovarian cancer based on intraperitoneal administration of chemotherapy drugs (Method of chemotherapy for ovarian cancer, AS 1693742 dated 11.04.89, Sidorenko Yu.S., Golotina L.Yu.), chosen by us as a prototype.

The method is carried out as follows. After completion of the operation in the region of the left hypochondrium along the anterior axillary line, retreating from the lower edge of the 11 ribs 2-3 cm down, a puncture is made from the skin of the entire thickness of the anterior lateral wall of the abdomen with a thick needle under the vision control so that the tip of the needle enters the free abdominal cavity. A thin polyethylene catheter with a diameter of 3 mm is passed through the lumen of the needle into the abdominal cavity. Then the needle is removed and the catheter is pulled into the abdominal cavity so that the free end is 10-12 cm. The catheter is cut off from the outside so that the free end protrudes above the skin level by 3-6 cm. Similar manipulation is also performed in the right hypochondrium region. Then the abdominal cavity is tightly closed. In the postoperative period for the period of chemotherapy, the outer ends of the catheters are left open. Conduct a massive continuous administration of chemotherapy for a long time (drip) through the microcatheters for 7-10 days: TioTef 60-80 mg per day, cyclophosphamide 400-800 mg per day, sarcolysin 40-50 mg per day with subsequent control of the introduction of the indicators Blood to the lower level of white blood cells 3000 once a week. The course doses of chemotherapy drugs, and the sequence of their administration depend on the prevalence of the process, the degree of surgical intervention.

However, patients with ovarian cancer, mainly elderly people with a flabby abdominal wall, therefore microcatheters quickly drop out, which limits the necessary chemotherapy courses. Flabbiness of the abdominal wall due to its stretching is observed in long-suffering patients, especially with ascitic forms of ovarian cancer, and often gave birth to women, especially those bearing a large fetus. The second important point is the psychological tension associated with the microcatheters that have been drawn onto the abdominal wall, and also the fear of their inadvertent extraction.

It is an object of the present invention to improve immediate and long-term results of treatment of patients with advanced ovarian cancer.

The goal was achieved by the fact that patients with a common process of ovarian cancer perform the first stage of the operation with the formation of a drainage system with the removal of the drainage tube through the cervical canal and the micro-irrigator through the posterior fornix. The second stage of treatment for patients with an established drainage system is chemotherapy. To do this, 200 ml of blood is taken from an ulnar vein in an empty stomach in a sterile standard vial with a gliggicir, and blood plasma is obtained by sedimentation. The erythrocytic mass is returned to the patient by intravenous drip. From the blood plasma under sterile conditions, lymphocytes are isolated. Plasma, devoid of cells, is incubated with cytostatics at 37 ° C for 30 minutes and reinfused intravenously with droplets. The introduction of platinum drugs is carried out against a background of standard hyperhydration and forced diuresis.

To the lymphocytes isolated from the blood plasma of patients, proleukin is added, placed in a CO 2 incubator and held for 24 hours, after which, i.e. One day after the administration of cytostatics on cell-free autoplasma, reinfusions are made to the patient through a micro-irrigator, which is withdrawn through the posterior arch.

Analysis of known methods of treatment of ovarian cancer and developed allows us to state that the proposed method is novel, which consists in the combination of a systemic intravenous injection of cytostatics, biotransformed autoplasma, devoid of cellular elements, with LAK therapy delivered directly to the region of malignant process that allows one to act even On chemoresistant tumor cells.

In the available sources of information from Russia, CIS countries and abroad, indications of such a method of improving the immediate results of treatment of advanced ovarian cancer with simultaneous objective reduction of toxic side effects of chemotherapy and an increase in the 5-year survival of patients were not detected.

The invention is industrially applicable, since it can be repeatedly reproduced and repeated in medical institutions of a specialized and therapeutic profile.

THE METHOD IS PROVIDED AS FOLLOWS:

After the bimanual, ultrasound examination of the pelvic organs and cytological analysis, detection of a common malignant process of the ovaries, the patient with the first stage undergoes operative treatment in the amount of supravaginal amputation of the uterus with appendages and omentectomy. Immediately after supravaginal amputation of the uterus with appendages from the side of the abdominal cavity, a drainage tube 0.5-0.7 cm in diameter and 50 cm in length is inserted into the cervical canal culvert from the top down into the vagina. The tube from the side of the vagina is grasped by the clamp and stretched to the exit from it. The upper end of the tube from the side of the abdominal cavity in the end position lagged behind the upper edge of the cervix of the cervix so that after its suturing the tube was located above the seam line by 1.5-2 cm. Draining through the cervical canal was combined with a microirror derived through the posterior arch. For better fixing of the drainage pipes, a horizontal lintel was used - the ligature, which, resting on the back wall of the cervix, kept the drains in the given direction. The micro-irrigator was used to feed the solutions of chemotherapeutic agents into the abdominal cavity.

A week after the operation, the patient from the ulnar vein on an empty stomach is taken 200 ml of blood in a sterile standard vial with a gliggicir, the method of sedimentation obtains blood plasma. The erythrocytic mass is returned to the patient by intravenous drip. From the blood plasma under sterile conditions, lymphocytes are isolated. Plasma, devoid of cells, is incubated with cytostatics: carboplatin 150 mg / m 2 + cyclophosphamide 1000 mg / m 2 at 37 ° C for 30 min and reinfused intravenously with drip. The introduction of platinum drugs is carried out against a background of standard hyperhydration and forced diuresis.

To lymphocytes isolated from the blood plasma of patients, 1.2 mg of proleukin are added in complete nutrient medium, placed in a CO 2 incubator and held for 24 hours, washed with sterile saline, after which, i.e. One day after the administration of cytostatics on cell-free autoplasma, reinfusions are made to the patient through a micro-irrigator removed through the posterior arch. This sequence of procedures is repeated every 3 weeks 4 courses, then every 6 weeks - 6 courses.

For the proof we give an extract from the case histories, confirming the clinical effect of the treatment by the proposed method.

Example of clinical use

Patient N., 52, entered the gynecological department of the Rostov Oncology Research Institute in September 2001 with the diagnosis: ovarian cancer of III-IV stage. When admission is objective: the large size of the abdomen due to the presence of ascites in the abdominal cavity, pale skin, shortness of breath, weakness. At palpation of the abdomen, a tuberous tumor is defined, reaching the upper border to the navel, the epigastric region is palpated, a tuberous tumor, a metastatically altered large epiploon, is palpated separately. The patient was laparotomy. 8 liters of ascites were evacuated. Operative intervention is performed in the volume of supravaginal amputation of the uterus with appendages. Immediately after amputation of the uterus with appendages from the abdominal cavity, a drainage tube with a diameter of 0.7 cm and a length of 50 cm was passed down to the vaginal canal culvert from the top down into the vagina. The tube from the side of the vagina was stretched out until it emerged from it. The upper end of the tube from the side of the abdominal cavity in the final position lagged behind the upper edge of the cervix of the cervix so that after its suturing the tube was located above the seam line by 2 cm. Draining through the cervical canal was combined with a microirror derived through the posterior arch. To better fix the drainage pipes, a horizontal lintel was used - the ligature, which, resting on the back wall of the cervix, kept drainage in the given direction. Stitching of the cervix was performed with separate catgut catgut sutures. Then we made peritonization. Histological analysis of the removed preparation №429422-27: moderately differentiated papillary cystadenocarcinoma; №429428-9 - the layers of the cancer cells are on the tuber's serosa.

A week after the operation, the patient from the ulnar vein on an empty stomach was taken 200 ml of blood in a standard sterile bottle with a glycemic, the method of sedimentation obtained a blood plasma. Erythrocyte mass intravenously drip reinfused the patient. From the blood plasma under sterile conditions, lymphocytes were isolated. Plasma, devoid of cells, was incubated with cytostatics: carboplatin 150 mg / m 2 + cyclophosphamide 1000 mg / m 2 at 37 ° C for 30 min and reinfected the patient intravenously with drip. The introduction of platinum drugs was carried out against a background of standard hyperhydration and forced diuresis.

To lymphocytes isolated from the blood plasma of the patient, 1.2 mg of proleukin was added in complete nutrient medium, placed in a CO 2 incubator for 24 hours. Then washed with sterile saline, and then reinfused the patient through a micro-irrigator, withdrawn from the posterior fornix. This sequence of procedures was repeated every 3 weeks 4 times, then every 6 weeks - 6 more times. Each time the administration of platinum drugs was carried out against a background of hyperhydration with forced diuresis. During the course of chemotherapy, blood counts were examined. The level of leukocytes did not decrease below 3,500.

The proposed method was used to treat 26 patients aged 46-60 years with advanced ovarian cancer. All patients were with a verified diagnosis. The predominant morphological variant of the tumor in 85% of cases was cystadenocarcinoma of moderate low degree of differentiation. Specifying the diagnosis of the degree of prevalence of the process according to ultrasound allowed to determine in patients with stage III-IV cancer.

In order to objectify the effect before the treatment, all patients underwent examination in mirrors, rectovaginal examination, general and biochemical blood tests, chest X-ray and excretory urography, radioisotope study of kidney function, pelvic ultrasound, pelvic lymphatic system and para-aortic divisions, puncture Posterior arch with morphological examination.

Immunological studies showed that after an incubation of plasma lymphocytes with proleukin for 24 hours, an increase in the amount of cytotoxic subpopulation of lymphocytes (CD8 +) and of IL-2 receptors (CD25 +) was detected. In the blood of patients during the treatment, an increase in the functional activity of T and B cells was noted. Progression of the process was not detected in any case. The five-year survival rate of patients was 51.3%.

Improving the results of treatment seems to us as a combination of various positive factors, consisting in the combination of the action of chemotherapeutic agents and the immunomodulating agent, which makes it possible to efficiently act on residual foci of a malignant tumor.

The technical and economic effectiveness of the "Ways to treat common ovarian cancer" is that:

  • Duration and quality of life of patients increases;
  • The toxic side effects of antitumor therapy decrease;
  • The time of chemotherapy is reduced, since there is no need to take breaks in treatment due to the absence of leukopenia;
  • Immunostimulating effect associated with activation of cytotoxic subpopulations of lymphocytes is noted.

CLAIM

The method of treatment of advanced ovarian cancer, including the operation with the formation of a drainage system and the use of chemotherapy, characterized by the fact that the first stage is carried out surgical treatment with the removal of the micro-irrigator through the posterior fornix, two weeks later begin chemotherapy: on the first day of autoplasmochemotherapy with cyclophosphamide at a dose of 1000 mg / m 2 And carboplatin at a dose of 150 mg / m 2 on a plasma devoid of cellular elements, and lymphocytes isolated from blood plasma are incubated with 1.2 mg of proleukin for 24 hours and administered on the second day into the abdominal cavity via a microarigator, this sequence of procedures being repeated Every 3 weeks, 4 courses, then every 6 weeks, 6 courses.

print version
Date of publication 06.01.2007gg