Method for treatment of relapses in oncogynecological patients

FIELD: medicine, oncology, gynecology.

SUBSTANCE: method involves trepanopuncture of flank bone wing, aspiration of bone marrow suspension in the amount 150-200 ml followed by incubation of suspension with chemopreparations cisplatin and cyclophosphan at temperature 37°C for 40 min in doses above therapeutic ones. Doxorubicin is not incubated with bone marrow suspension and chemopreparations are administrated separately by intravenous route, by drops in indicated order in day when the bone marrow suspension has been taken, and this procedure is repeated with interval for 3-4 weeks but totally 4 times per one treatment course. Proposed method provides attaining the stable anti-tumor effect up to the complete tumor regression in this category of patients showing high tolerance to chemotherapy, and in practical absence of adverse toxic responses. Invention can be used in treatment of patients with relapses of ovary and uterus body cancer in case absence effectiveness of other methods of treatment or in case of their low effectiveness.

EFFECT: improved method of treatment.

2 ex

 

The invention relates to medicine, namely to gynecology, and can be used for the treatment of patients with recurrent ovarian cancer and cancer of the womb, when other treatment methods have been exhausted or are ineffective results.

Despite the fact that more than 50% of patients with disseminated ovarian cancer achieve a complete clinical remission after modern comprehensive treatment, most of them within the first three years developing a relapse (Urmancheyeva A.F. Modern chemotherapy of ovarian cancer. Practical Oncology. T3, No. 4, 2002).

There is a method of treatment of ovarian cancer, and recurrence of the disease using autohemotherapy (AGHT) (Dolmatova O.K. Autohemotherapy advanced ovarian cancer: author. dis. Kida. the honey. Sciences. Rostov-on-don, 1995). The method consists in the fact that in the postoperative period spend intravenous drip combination of 4 drugs under the scheme CMFV, incubated with Autocraft; 1 time per week for 4-5 weeks, that is, treatment - 4-5 infusions: vinblastine, 5-10 mg, or vincristine 5-10 mg; cyclophosphamide - 600-800 mg/m2; 5-fluorouracil - 500-750 mg/m2; methotrexate - 15-25 mg/m2.

The use of autohemotherapy in patients with recurrent ovarian cancer in the state of the generalization of the tumor process, which is considered Inka is labelname, allowed to achieve remission in more than half of the patients (53.3%). Another 1/3 of patients (33.3%) occurred stabilization process. Only 13.3% of patients had a further progression of the disease. However, a significant disadvantage of the use of IGHT is high toxicity. So, the nausea and vomiting of varying severity were observed in 42.4%, diarrhea, stomatitis, hepatotoxicity, alopecia - in isolated cases. Hematological complications in the form of radiation in patients with recurrent amounted to 76.6%. The application of the method limits the generalization of the tumor process, improves the condition of patients, but does not effectively prevent recurrence even in the nearest period of time.

There is a method of treatment of patients with ovarian cancer stage III-IV using infohesiveep (Galabova YEAR Neoadjuvant lymphocytotropic in complex treatment of patients with ovarian cancer stage III-IV. Abstract of dissertation for the degree of candidate of med. Sciences. Rostov-on-don, 2002), including intravenous chemotherapy on autolife: cisplatin 100 mg/m2, doxorubicin 40-50 mg/m2, cyclophosphamide 600-800 mg/m2. Lemonvate was carried out once. Complete regression was achieved in 34.2% of patients, partial regression achieved at 42.4%. Thus, the efficiency of such a method of treatment of ovarian cancer was 76.7%. P and it should be noted some shortcomings of the method: it is not always possible to drain General thoracic lymphatic duct, the lack of adequate for carrying out autolymphochemotherapy (ALHT) volume autolamp, failure patient from surgery. In addition, the incidence of relapse was 48% after holding ALHT. Hematologic toxicity when using infohesiveep was 30%. Diarrhoeal disorders appeared at 13.6%. Nephrotoxicity was observed in 2.7%. The method provides the regression of the tumor, but does not prevent further occurrence of relapses.

Known "Method of treatment of cancer of the womb" (see patent No. 2195269 from 10.06.02 bull. No. 26), including ALHT patients with common forms of endometrial cancer stage III. The essence of the method lies in the fact that in the preoperative period increased 2 times the standard total dose rate drugs consisting of: cyclophosphamide, 5-fluorouracil and methotrexate, incubated with autolite patient and injected, drip for 2 hours, 2 times a week with an interval of 2-3 days, just 4 treatments. The method allows to reduce the size of the tumor and the degree of tumor, however, the application of this method of treatment in the preoperative period does not affect the further prevention of recurrences of cancer of the womb.

There is a method of treatment of patients with locally advanced breast cancer using the method of automarken is terapii (AMHT), chosen as a prototype (Nikolaeva N.V. Neoadjuvant automalaxoare in complex treatment of patients with locally advanced breast cancer. The dissertation on competition of a scientific degree of the candidate of med. Sciences. Rostov-on-don, 2003), including intravenous chemotherapy on bone marrow suspensions according to the scheme: cyclophosphamide 800 mg/m2in the 1st and 8th days, doxorubicin 40 mg/m2in the 1st and 8th days of treatment, 5-fluorouracil 750 mg/m2in the 1st and 8th days. Doxorubicin was subjected to incubation with myelosis in a volume of 100 ml, cyclophosphamide and 5-fluorouracil were incubated in another vial myelosis the same amount. Incubation was carried out at a temperature of 37°C for 40 minutes, with subsequent intravenous drip. Efficiency was observed in 81.2% of cases, of which 6.2% - total regression of the tumor, partial - 75%. Analysis of toxic complications showed no reaction caused AMHT. Leukopenia was noted in 43.7% of cases of anemia were observed. Neutropenia was noted in 34.3%. Complications such as stomatitis and diarrhoea, was missing.

The known method AMHT allows to reach in the preoperative period in some cases more complete and partial regression of the tumor, reduces radiation and toxicity of chemotherapy, however, has never been used for the treatment of relapse in onkalo the systematic diseases, moreover, not been used for the treatment of oncological patients in the treatment of recurrent ovarian cancer and uterine body.

The aim of the invention is to improve the immediate and remote results of treatment of patients with recurrent ovarian cancer and cancer of the womb.

This goal is achieved by the fact that these patients produce tremenously wing of the Ilium, aspirinum 150-200 ml of bone marrow suspension, incubated at 37 ░ °C for 40 minutes with chemotherapy: cisplatin, cyclophosphamide in doses above therapeutic; doxorubicin not incubated with bone marrow suspension, chemotherapy is injected separately in the order given intravenous drip in a day intake of bone marrow suspension, the procedure is repeated with an interval of 3-4 weeks, only 4 times in the course of treatment.

The invention of "a Method for the treatment of relapse in oncological patients" is new, because it is unknown the level of medicine, namely chemotherapy patients with recurrent ovarian cancer and cancer of the womb.

The novelty of the invention lies in the fact that patients with recurrent ovarian cancer and endometrial cancer produce tremenously wing of the Ilium, aspirinum 150-200 ml of bone marrow suspension, incubated at 37 ░ °C for 40 minutes with chemotherapy: cisplatin, cyclophosphamide in doses above therapeutics is; doxorubicin is not incubated with bone marrow suspension, chemotherapy is injected separately in the order given intravenous drip in a day intake of bone marrow suspension, the procedure is repeated with an interval of 3-4 weeks, only 4 times in the course of treatment. Thus, the novelty of the invention lies in the fact that none of the known methods of treatment generalizovanih forms of development of tumor with recurrent ovarian cancer and endometrial cancer does not provide for the treatment of relapsed ovarian cancer and cancer of the womb using automalaxoare. The method provides the possibility of conducting a full course of chemotherapy, which is not always possible with conventional methods of chemotherapy, without nephrotoxicity, hematologic complications.

Known methods of chemotherapy in gynecology - autohemotherapy, autolymphocyte - usually used in the preoperative period of treatment and are not aimed at ensuring efficiency in the treatment of relapsed ovarian cancer and endometrial cancer, so our method differs from known methods of treatment and goals.

The invention of "a Method for the treatment of relapse in oncological patients is industrially applicable, as there may be many times repeated and used in the treatment of recurrent ovarian cancer and endometrial cancer and is epoisode in various medical institutions, especially with cancer: oncologic dispensaries, cancer research institutes.

"A method for the treatment of relapse in oncological patients" as follows: after antiseptic skin treatment lumbar gluteal region, under local anesthesia with 0.5% solution of novocaine produce tremenously Ilium and aspirinum 150-200 ml of bone marrow suspension. The obtained suspension was placed in a bottle with logician. Bone marrow suspension is subjected to incubation with cisplatin at a dose of 150-200 mg/m2and cyclophosphamide at a dose of 600-800 mg/m2at a temperature of 37°C for 40 minutes, after which the background overhydration and forced diuresis is entered patient intravenous drip. Doxorubicin incubation not be administered intravenously, drip dose of 60-70 mg/m2. Polychemotherapy is held on the day of sampling bone marrow suspension with an interval of 3-4 weeks.

Examples of a specific implementation method can serve as a statement of case histories.

1. Patient Shepeleva G.M., born in 1960, he enrolled in the Department of gynecology of RNII 27.01.2004 complaining of intermittent abdominal pain.

From the anamnesis: ill since late 2001, when there was pain in the right hypochondrium, weight loss. In September 2002, a patient asked RNII, where the survey was zapados the n diagnosis: ovarian cancer. 10.09.2002 performed surgery in the amount of supracervical amputation of the uterus with appendages, omentectomy. The peritoneal cavity is drained microirrigation. Histological analysis No. 662080-81, 83-84: poorly differentiated serous papillary cystadenocarcinoma, in the great omentum - metastasis of cancer to the above structure. In the postoperative period, from September 2002 to January 2003, the patient received 6 cycles of intraperitoneal chemotherapy with platinum drugs and taxonomy: cisplatin 150 mg/m2, paclitaxel 210 mg/m2. Until January 2004, he was feeling quite well. At the end of the month appeared lower abdominal pain, the patient asked RNII.

Admission: General condition is satisfactory. Height - 158 cm, weight 85 kg Skin pale pink, dry. Peripheral lymph nodes, available palpation, not increased. Stable hemodynamics. Vesicular breathing in lungs. Abdomen moderately painful in the lower divisions, physiological functions are normal.

Status genitalis: external genitals without features. In mirrors: the cervical stump clean, moderately mobile. PV: in the pelvis, at the location remote of the uterus and adnexa palpated dense, hilly, sedentary education 6,0×5,0 see Codes free.

Laboratory data: 1. General analysis of blood from 28.01.2004: Hemoglobin - 142 g/l, Aritri what you're 4,8×1012/l, Leucocytes - 6,1×109/l, ESR - 16 mm/h, P./poison. to 3.5%, S./poison. - 59%, Eosinophils - 7,5%, Monocytes - 5%, Lymphocytes 25%. 2. Biochemical analysis of blood from 28.01.2004: Glucose - 4.4 mmol/l; Urea - 4.7 mmol/l; Total protein - 73 g/l; Creatinine - 113,8 Ámol/l; Alkaline phosphatase and 47.0 E/l 3. Analysis of CA-125 from 20.01.2004: CA-125=160,0 IU/ml 4. Ultrasound examination of abdominal cavity and small pelvis from 20.01.2004, conclusion: postoperative local recurrence of ovarian cancer 6,1×are 5.36 cm; diffuse changes of a liver, kidneys; chronic cholecystoenteric.

After a survey of diagnosis: R/o ovarian cancer, St.IIIC, gr. 2, the state after multimodality treatment (surgery + 6 courses XT). Local recurrence. T3cN1M0.

29.01.2004 held 1 course automalaxoare. 150 ml of bone marrow suspension intravenous drip introduced 150 ml of cisplatin, 800 mg of cyclophosphamide. Intravenous introduced 60 mg of doxorubicin. The introduction of chemotherapy the patient satisfactorily. 30.01.2004 noted nausea, single vomiting. Conducted detoxification therapy. 02.02.2004 the patient was discharged with recommendations. The turnout in RNII 3 weeks to conduct 2 course AMHT.

19.02.2004 patient came for another course of chemotherapy. Complaints about minor weakness.

Objectively: General condition regarding udovletvoritel is Noah. Height - 158 cm, weight - 81 kg (observed weight loss of 4 kg). The skin is pale pink, dry. Peripheral lymph nodes, available palpation, not increased.

Status genitalis: external genitals - without features. The stump of the cervix in the mirrors clean. PV: behind the cervical stump is determined by the dense hilly education about 4.0 cm in diameter. In the vaults - free.

Laboratory data: 1. General analysis of blood from 19.02.2004: Hemoglobin - 138,6 g/l; Erythrocytes - 4,4×1012/l; Leucocytes-4,5×109/l; ESR - 15 mm/h; P./poison. - 10%; C./poison. - 58%; Eosinophils - 1%; Basophils - 1%; Monocytes - 9%; Lymphocytes - 21%. 2. Blood biochemistry from 19.02.2004: Glucose - 4.4 mmol/l; Urea - 5.2 mmol/l; Total protein - 85 g/l; Creatinine - to 95.3 mmol/l 3. Analysis of CA-125 from 19.02.2004: CA-125=20,5 IU/ml 4. Ultrasound examination of abdominal cavity and small pelvis from 19.02.2004, conclusion: the recurrence p/o ovarian cancer - posterior to the cervical stump lazerette hypoechoic education with irregular, indistinct contours to 4.0 cm in diameter.

After the examination, diagnosed as: p/o ovarian cancer, St.IIIC, gr. 2, the state after combined treatment. Local relapse status after 1 year AMHT 2thline T3cN1M0. Partial regression of the tumor.

2. Patient Kramarenko PS, born in 1950, he enrolled in the Department of gynecology of RNII 09.01.2004 with complaints of lower abdominal pain, bleeding from the floor of the new ways, pain in the lumbar region to the left, body temperature rise up to 38 S. history: sore since 2000, when first appeared abdominal pain, weakness. January 2002 - heavy menstruation. Surveyed in the Oncology center, Mariupol, where 29.05.2002, cancer of the womb transaction in the amount of panhysterectomy. Histological analysis No. 12552: moderately differentiated adenocarcinoma. In p/o period held sachitano-beam treatment. Until January 2003, the patient felt well, then there was bleeding from the genital tract, abdominal pain. Conducted refresher course With intracavitary therapy on the area of the p/o scar (SOD=60 Gy). Treatment without effect. The patient independently came to RNII for treatment.

Objectively: General condition is satisfactory. Height - 165 cm, weight - 95 kg Skin normal color, moist. Peripheral lymph nodes, available palpation, not increased. Stable hemodynamics. In the lungs vesicular breathing. The abdomen is soft, painful to palpation in the lower sections. Chair, diuresis normal.

Status genitalis: external genitals without features. The vagina ends with "blind bag", from the genital tract moderate spotting. PV: the vaginal stump fixed, sharply painful, bumpy. In place of the deleted uterus - relapse 7,0൳,0 see Pronounced infiltration of parametrial, to the left, almost to the walls of the pelvis.

Laboratory data: 1. General analysis of blood from 12.01.2004: Hemoglobin - 124 g/l; Erythrocytes - 4,1×1012/l; Leucocytes - 5,0×109/l; Platelet - 221,4×109/l (54‰); P./poison. - 60%; C./poison. - 9%; Eosinophils - 3%; Monocytes - 9,5%; Lymphocytes To 18.5%. 2. Blood biochemistry from 12.01.2004: Glucose - 5.2 mmol/l; Urea - 3.2 mmol/l; Total protein - 73 g/l; Creatinine - 118 Ámol/l; Alkaline phosphatase - 16,2 E/l 3. Ultrasound examination of abdominal cavity and small pelvis from 14.01.2004, conclusion: the recurrence p/o cancer of the womb of 3.78×4,2×7,0 cm, hydronephrosis on the left, hepatomegaly, diffuse changes in the liver, chronic cholecystoenteric.

After the examination diagnosed with: p/o cancer of uterine body St.IIIA, gr condition after combined treatment. Local recurrence. T3aN0M0

27.01.2004 conducted 1 year AMHT. 200 ml of bone marrow suspension introduced: 200 mg of cisplatin; 800 mg of cyclophosphamide. /Drip introduced 70 mg of doxorubicin. The introduction of drugs the patient satisfactorily. In the subsequent three days of nausea, vomiting, the patient was not observed, the General condition was assessed as satisfactory. Significantly decreased bleeding from the genital tract, decreased pain. 2.02.2004 patient was discharged in satisfactory condition with recommendations: nab is Eugenie oncologist at the place of residence, control the level of blood leukocytes in 1 week. The turnout in RNII 3 weeks to conduct 2 course AMHT.

26.02.2002 patient hospitalized in the Department of gynecology for holding 2 course AMHT. Complaints about poor, serous nature of the discharge from the genital tract minor pain in the lumbar region on the left. In General, the patient noted significant improvement in well-being (absence of pain during urination, pain in the lower abdomen).

Laboratory data: 1. The CBC dated 26.02.2004: Hemoglobin - 110,4 g/l; Erythrocytes - 3,9×1012/l; Leucocytes - 3,0×109/l; Platelet - 245,7×109/l (63‰); ESR 25 mm/h; P./poison. 14.5 percent; C./poison. - 58%; Eosinophils - 0,5%; Monocytes - 9,0%; Lymphocytes Is 17.5%. 2. Blood biochemistry dated 26.02.2004: Glucose - 4.4 mmol/l; Urea - 3.7 mmol/l; Total protein - 73 g/l; Alkaline phosphatase is 32.3 U/l 3. Ultrasound examination of abdominal cavity and small pelvis from 01.03.2004, conclusion: the recurrence p/o cancer of uterine body 3,47×4,55×4,62 cm, left hydronephrosis, chronic cholecystoenteric.

After the examination, diagnosed as: p/o endometrial cancer, St.IIIA, gr condition after combined treatment. Local relapse status after 1 year AMHT. T3aN0M0. Partial regression of the tumor.

The proposed method treated 11 patients with recurrent ovarian cancer, 2 patients with recurrent endometrial cancer. While the shallow place gastroenterological complications - nausea, vomiting in 5 patients, which accounted for 38.4 per cent. In any case, was not observed nephrotoxicity. Hematological complications in the form of radiation mild degree was noted in 2 patients (15.3 per cent). In all cases the treatment was effective partial regression of tumors was observed in 9 patients (69.2 per cent); full regression - in 4 patients (30,8%). The progression of the disease is not observed in any case.

Technical and economic efficiency "method of treatment of relapse in cancer patients" is the ability to treat patients in this category with no effect to previously used methods of chemotherapy; significantly reduce toxic side effects.

Treatment of relapse in oncological patients, including chemotherapy, characterized in that the patients make tremenously wing of the Ilium, aspirinum 150-200 ml of bone marrow suspension, incubated at 37 ░ °C for 40 min with chemotherapy: cisplatin, cyclophosphamide in doses above therapeutic; doxorubicin not incubated with bone marrow suspension, chemotherapy is injected separately in the order given intravenous drip in a day intake of bone marrow suspension, the procedure is repeated with an interval of 3-4 weeks, only 4 times in the course of treatment.



 

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FIELD: medicine, cardiosurgery.

SUBSTANCE: the present innovation deals with complex procedures for carrying out open-heart operations associated with high blood losses and considerable requirement for blood-substitution therapy. It is necessary to carry out preoperational autoblood sampling in cardiosurgical patients due to a single exfusion of 5-10% volume of patient's circulating blood and its conservation, moreover, 1-2 d before autoblood sampling it is necessary to conduct total hypoxic sample, detect the values of oxygen balance and lactate concentration in blood serum and at its values being SpO2>85%, SvO2>60%, O2EI<30 and the absence of lactate concentration growth at the background of 40-min-long respiration with hypoxic gaseous mixture with 10%-content of oxygen one should consider tolerance to hypoxia to be high and sample autoblood at the quantity of 10% against total volume of circulating blood; at physiological ability of a patient to breathe for 40 min with hypoxic gaseous mixture with 12%-content of oxygen it is possible to consider tolerance to hypoxia to be average and sample autoblood at the quantity being not more than 7% against the volume of circulating blood, and at physiological ability of a patient to breathe with hypoxic gaseous mixture only at the content of oxygen being under 14% tolerance to hypoxia should be stated to be low and, thus, one should sample not more than 5% against the volume of circulating blood. The innovation decreases postoperational complications, increases efficiency of hemotransfusional therapy due to individualized approach for detecting optimal quantity of autoblood sampled.

EFFECT: higher efficiency of sampling.

3 ex

FIELD: medicine, oncology.

SUBSTANCE: the present innovation deals with treating patients with generalized skin melanoma at single and multiple cerebral metastases and extracerebral lesions. The method includes systemic immunochemotherapy. For this purpose, on removing a single cerebral metastasis and melanomatous focus or at multiple cerebral lesions when operation is contraindicated it is necessary to carry out a 2-wk-long course of autohemoimmunochemotherapy, that is: 400 ml patient's autoblood should be sampled into a vial with hemoconservant and after sedimentation it should be divided into 2 equal fractions - plasma and autologous cell suspension (ACS). In separate vials it is necessary to prepare 3 media - 200 ml autoplasma (medium N1) and per 100 ml ACS (medium N2 and N3). One should incubate for 1 h in thermostat at 37° C medium N1 with 100 mg carmustine (mixture N1), medium N2 - with 25 mg metothrexate and 1 mg vincristine (mixture N2), medium N3 - with Reaferon at the dosage of 5×106 IU Reaferon (mixture N3). On the 1st d of the course one should inject mixtures intravenously by drops successively every mixture per 60 min, mixture N2 should be injected repeatedly on the 8th d of the course, mixture N3 should be injected by drops along paracetamol intake thrice weekly during the whole 2-wk-long course of therapy. Additionally, one should fulfill intravenous infusions of 150 mg carboplatin and 15 mg bleomycin upon 200 ml autoblood by drops on the 2nd and 4th d of the course, correspondingly. Totally, one should carry out 3-6 courses. The innovation provides stable regression of neurological symptoms due to decreasing the volume of cerebral metastasis and reactive perifocal cerebral edema and increasing relapse-free and metastasis-free periods and, also, life period in patients.

EFFECT: higher efficiency of therapy.

2 ex

FIELD: medicine, virology, biochemistry.

SUBSTANCE: invention relates to a method for inhibition of viruses growth and/or virulicide effect. Method involves biotransformation of pyrazine nucleotide analog of the formula [2] and pyrazine nucleoside analog of the formula [3z] involving decomposition and phosphorylation resulting to preparing analog of pyrazine nucleotide of the formula [1b] and above said effect. This method can be used as a method for treatment of viral infections. Also, analog of pyrazine carboxamide or its salt can be used as an agent for prophylaxis and treatment of viral infections. Invention provides the development of a novel anti-viral agent and methods for its using.

EFFECT: valuable medicinal properties of analogs, improved method for inhibition.

50 cl, 80 ex

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