Method for treating oncological patients with vaginal tumor lesion
FIELD: medicine, oncology.
SUBSTANCE: one should carry out chemoradiation therapy at applying a cytostatic preparation followed by distance and intracavitary irradiation. Depending upon development of tumor lesion during the first 3 or 6 d it is necessary to conduct monochemotherapy only due to introducing proxiphen together with dimethyl sulfoxide at weight ratio of 4.5-5.0 : 0.5-1.5, correspondingly by applications in "Coletex" napkins. Moreover, a napkin should be pre-impregnated in 20%-dimethylsulfoxide solution and fixed with a tough vaginal tamponade by changing napkins every 24 h. Then since the 4th d or the 7th d simultaneously with application it is necessary to carry out contact irradiation and distance impact onto minor pelvis every 4-6 h at single focal dosage (SFD) being 2 Gy at 10 seances 5 times/weekly with high-activity sources of SFD 2 Gy. The innovation provides tumor regress under conditions of no therapeutic complications, thus, improving patients' quality of life.
EFFECT: higher therapy.
The invention relates to medicine, namely to Oncology, and can find application in the treatment of predominantly common gynecological cancer, burdened with extensive tumor lesion adjacent to the primary tumor lesion anatomic structures, which makes impossible the implementation of radical treatment programs.
Patients with extensive lesions of the vagina are one of those groups where the possibility of holding a special treat as combined and radical combined radiation therapy are severely limited due to the significant volume of the tumor, the true boundaries of which far exceed the visually defined, disruption of the natural topography of the pelvic organs, disorders of adequate blood supply to the tumor due to spontaneous degradation and relative reduction of radiosensitivity in hypoxia.
A known method of treatment of common gynecological cancer for several decades continues to be radical concomitant radiation therapy, based on the alternation of remote and intracavitary radiation therapy. (Ameno, Volvieron. Radiation therapy in gynecology and oncourology. Saint-Petersburg. Ed. "Folio". 2002, P. 166-168).
2 / 3 of patients described categories at 20 Gy not Udet what I achieve necessary for the beginning of intracavitary gamma therapy (ITGT) level regression. Submucosal infiltration vaults and walls of the vagina, the tumor mass on the mucous membrane of the vaginal tube, the rigidity of the walls of the vagina, often it stricture impede beginning of intracavitary irradiation with adequate accommodation of endostatin require significant dose reduction from WPHT that reduces the overall therapeutic effect. One-third of patients are only palliative program exposure, 20% of patients due to the lack of conditions for VPGT must be limited to holding only remote exposure.
There is a method of treatment of cancer patients with neoplastic lesions of the vagina, including chemoradiation therapy with cytostatic, remote and intracavitary irradiation (Gorbunov V.V. Optimization of combined radiotherapy of locally advanced cervical cancer and recurrent ovarian cancer with chemotherapy in therapeutic mode of thesis. on siskan. academic Art. MD, M., 2002, s, prototype)
The effectiveness of the method for this category of patients is insufficient, because the proposed dose irradiation with simultaneous introduction of cytostatic intravenously are of limited use in patients with concomitant diseases and disorders of the kidneys, liver, cardiovascular system, leading in some cases to an important heme is ideological, gastrointestinal, urological complications, the cost of maintenance is high and unaffordable for many patients.
The technical task of the present invention is to develop effective and at the same time gentle method of treatment of cancer patients with lesions of the vagina, allowing in some cases to implement a course of radical combined radiation therapy without severe reactions and complications due to the increase in pace and volume regression of the tumor and the timely appearance of conditions for adequate VPGT or other radical/conditionally radical program of therapy.
For this purpose, the method of treatment of cancer patients with neoplastic lesions of the vagina, including chemoradiation therapy with cytostatic, remote and intracavitary irradiation, proposed for the first 3 or 6 days, depending on the distribution of tumor destruction, to spend only a monochemotherapy, as supplied by the local cytostatic to apply the applique cloth Collex" entered PROXIFIER and dimethylsulfoxide at a mass ratio of 4.5 to 5.0:0.5 to 1.5, respectively, with a napkin previously advanced to moisten 20% solution of dimethyl sulfoxide and locking by means of tight tamponade vagina, change cloths to produce to the each 24 hours 4 or 7 nights at the same time with application to radiation, including contact exposure to sources of high activity GENUS 2 Gy and remote radiation exposure after 4-6 hours on the pelvis GENUS 2 G 10 sessions, 5 times a week.
For patients with primary cervical cancer with tumor lesions of the vagina and then continue to treat the conduct of combined radiotherapy in the radical doses.
The choice of the drug "PROXIFIER" due to the conformity of the obtained experimental data a number of requirements to the choice of the cytotoxic agent, which in the conditions of use in combination with exposure to significant volume must have its own high antitumor activity, mild General toxicity, especially hematologic and gastrointestinal, do not induce ulcerative-necrotic changes surrounding healthy tissues by prolonged exposure in contact, in the concentrations used to have radiomodification effect, potentsiruya antitumor activity of ionizing radiation.
We used napkins "Kreteks" was a textile base with a deposited layer of dimethyl sulfoxide and anticancer drug PROXIFIER. PROXIFIER is a derivative of caffeine hydrochloride, gamma-dimethyl-aminopropionic ether-oxycodeine. The mechanism of action is cytotoxic (antimitoticescoy) drug class antimetabolites of nucleic acid metabolism. PROXIFIER inhibits the activity of phosphodiesterase cyclic monophosphate (camp), which leads to increased intracellular levels of camp - one of the natural compounds that control the proliferation and differentiation of cells. PROXIFIER causes significant changes in the generational cycle of tumor cells, consisting in the elongation cycle (especially presinteticescuu and synthetic phases) and in the delay cells in postsinteticescuu phase.
Using proxiphen in the form of a therapeutic complex Collex"containing printed on a textile basis (cloth) biocompatible polymer is a polysaccharide alginate sodium and cytostatic, with the application of its application, allows you to reach the electoral prolonged chemotherapeutic effect on the tumor in average therapeutic dose at minimum General toxic action due to the lack of significant absorption of the drug into the blood stream when the application method injection. The combination of prolonged local Mat-PROXIFIER with radiation therapy in the previously described mode demonstrates and radiomodification effect used cytostatic, while creatures of the NGOs increase the rate and volume regression of the tumor.
To date, the proposed method of treatment 14 women recognized as incurable at the primary treatment. All were diagnosed with locally extensive tumors of the genital organs with lesions of the vaginal tube and the destruction of the vaginal portion of the cervix (cervical cancer (8 women, cancer of uterine body - 3, cancer of the vagina - 1, ovarian cancer - 1, colon cancer - 1). Carrying out the first stage of the treatment approach has allowed all patients to achieve significant positive effect is the partial regression of the tumor along the vaginal tube with a resolution of neoplastic stricture of the vagina, forming the vaginal portion of the cervix, thus came the conditions for this group of patients conditionally radical and palliative programs special treatment. In General, the treatment was effective in 80% women: complete clinical and cytological primary healing was achieved in 30% of patients, all of them alive with no evidence of progression at the present time, the observation period ranged from 18 to 24 months. Partial regression was achieved in 50% of patients, the time to disease progression ranged from 4 to 24 months., this progression in the area of radiation were detected only in one of them.
The essence of the proposed method is illustrated by clinical examples.
Ill the I D.O. A., born in 1955, history N 44962, was admitted to the hospital with suspected tumor of the vagina.
If the comprehensive examination diagnosed cervical cancer stage IIIB (T3bNxMo), vaginal-parametric variant with advanced tumor of the vagina to the lower third, the development of its full stricture involved parameters on both sides, pelvic lymphadenopathy. Colportage. Anemia 2 tbsp. impaired function of both kidneys 3-4 degrees.
Morphological diagnosis: No. 3023-402 - squamous cell carcinoma.
Concomitant diseases; ischemic heart disease. Hypertension stage 2, krizova for NC 1-2. Diabetes mellitus type 2, moderate flow. Chronic calculous cholecystitis. Obesity 3-4 degrees.
Consulted a medical physicist, PCT is impractical due to gross impaired renal function.
Given the amount of destruction and somatic status of the patient, the patient initially had planned symptomatic - hemostatic - radiation therapy.
Along with the comprehensive examination, the patient began to impose on the tumor in the vagina napkin "Kreteks", moistened with a 20% solution of dimethyl sulfoxide containing proxipen and dimethylsulfoxide at a mass ratio of 4.5:0.5 in. Recorded wipe with gauze swab, zabotivshihsya vagina at the maximum in zmoney depth (first day - 1.5 cm, 2 days - 3 cm). Change cloths were made every 24 hours. By the 3rd day appeared hyperemia, fibrinous film on the surface of the tumor, the tumor by palpation has somewhat softened, decreased the length of the stricture of the vagina (tamponade already at a depth of 3 cm). For 6 days the depth of the vaginal tube was 4 cm marked moderate hemostatic effect of termination contactless spotting from the vagina, allowing to start with 7-day radiation therapy, including contact exposure using colostate apparatus AGATE-WU" sources Co-60 high activity, GENUS 2 G on the surface of colostate (which corresponded to 250%-200% isodose), with the number of positions of the radiation source corresponding to the maximum length of the vaginal tube (7 day - 4 positions, on the 19 day - 8 items), and radial distance therapy (ESWL) in the 6 MeV LINAC, the sessions of which were held on the same day that contact exposure, after 4 hours, with 2 opposing fields 18×20 cm, with the lower margin of 1 cm below the entrance to the vagina, GENUS 2 Gy to the pelvis. Daily dose for vaginal tube, thus, was 4 Grams, in the centre of the pelvis - 2 Gr. Application proxiphen in the form of wipes "Kreteks" is not lost: the cloth was removed at the time of the session contact exposure, after which he again put her folded VDV is e, the parties containing cytostatic to tumor changed the front, the rear wall and the dome of the vagina, fixing a gauze pad was placed between the front and rear sheets of paper napkins. On weekends, when the irradiation was not carried out, a change of cloths produced every 24 hours as indicated above. A total of 10 sessions of irradiation as described above, with the rhythm of the radiation 5 times a week. The total dose from all exposure to the end of the stage was 20 Gy in the centre of the pelvis, 40 Gy to the vaginal tube. The number of applications of proxiphen was 20.
Gynecological examination after treatment in a specified way: the vulva with symptoms of moderate hyperemia. Edema, desquamation of the epidermis is not observed. Vaginal tube length 8 cm, managed to look in the mirror cervix - vaginal portion of it up to 6 cm in D, formed, large-rough, with irregular contours, the contact is not bleeding. The body of the uterus enlarged myomatous node to 14 weeks, the appendages are clearly not palpable due to obesity. The infiltrate in the left parametrium almost to the pelvic wall, the right is retained presence. Selection serous, scarce.
Achieved expressed positive results: hemostatic effect, reduction of tumor volume in 1.56 times according to ultrasound and x-ray computer is Oh tomography, with a resolution of the stricture of the vagina, the conditions for intrauterine gamma therapy. The patient changed her treatment plan with symptomatic conditionally radical chemoradiation therapy. Achieved an initial complete cure. During the control survey in December 2002, February, may 2003, April 2004, data for the progression of the cancer is not received. Quality of life is consistent with 1 tbsp. violations by ECOG.
Thus, by conducting the treatment in this way the patient locally advanced cervical cancer stage IIIb, recognized at the beginning of therapy incurable, that is not subject to special treatment, alive without recurrence for 1.5 years with good quality of life.
Sick, A.M., born in 1933, history N 3051, was admitted to the hospital in 2002 with a diagnosis of cervical Cancer IIb (T2bNxMo)senior Status after combined radiation therapy in 1993. The progression. Metastases to the vagina, inguinal lymph nodes. Colportage.
Morphological diagnosis No. 2345-7-8: squamous cell carcinoma moderate differentiation.
Comorbidities: Atherosclerotic cardiosclerosis. Calculous cholecystitis. A cyst of the left kidney. Varicose disease of the lower extremities.
If the comprehensive examination, the patient 70 years through 10 years after radical combined radiation Ter the FDI for cancer of the cervix IIb (T2bNxMo)Art. installed the progression of cancer, metastases to the vagina with the development of its incomplete stenosis, profuse hemorrhage from the vessels of tumors, metastases in the inguinal lymph nodes. Somatic status reduced to 3 degrees ECOG. The possibility of special treatment significantly limited (neoperabelna, PCT denied due to gross violations of kidney function, reserves radiation therapy are small, technical conditions for contact radiotherapy missing).
The patient began to sum the cytostatic PROXIFIER to the tumor of the vagina, the cloth is Collex", moistened with a 20% solution of dimethyl sulfoxide containing proxipen and dimethylsulfoxide at a mass ratio of 5.0:1,5, folded in half, the sides containing cytostatic agent, was applied to the tumor changed the front, the rear wall and the dome of the vagina, tight fixed position gauze pad, located between the front and rear sheets of paper napkins, through tight tamponade of the vaginal stump. Change cloths were made every 24 hours. By the 3rd day appeared hyperemia, a significant number of fibrinous film on the surface of the tumor in the dome, the tumor in the input palpation has somewhat softened, decreased the length of the stricture of the vagina (tamponade already at a depth of 3 cm), marked moderate hemostatics the rd effect of termination contactless spotting of the dome of the vagina, so we could start with 4 days of radiation therapy including reserves of tolerance, including contact exposure apparatus AGATE-WU" sources Co-60 high activity using thin colostate, GENUS 2 G on the surface of colostate (which corresponded to 250%-200% isodose), with the number of positions of the radiation source corresponding to the maximum length of the vaginal tube (4-5 items), and external beam irradiation (ESWL) in the 6 MeV LINAC, the sessions of which were held on the same day that contact exposure, after 4 hours, with 2 x counter fields 10×15 cm, with the lower margin of 1 cm below the entrance to the vagina, GENUS 2 Gy to the pelvis. Daily dose for vaginal tube was 4 Grams, in the centre of the pelvis - 2 Gr. Application proxiphen in the form of wipes "Kreteks" is not lost: the cloth was removed at the time of the session contact exposure, after which the newly imposed as described above. The total number of radiation sessions - 10, 5 times per week, total dose from all exposure to the end of the stage was 20 Gy in the centre of the pelvis, 40 Gy to the vaginal tube. The number of applications of proxiphen was 20.
The favorable effect, marked the cessation of bleeding was achieved partial regression (decrease in tumor volume by 34%). In the future the patient continued ESWL LEA 5 MeV inguinal lymph nodes to SOD 40 Gr. The patient is alive this is the time, during the year since the establishment of relapse, with no signs of further progression of the tumor process.
Patient LLP, born in 1941, andb 4465, was admitted to the hospital in 2003 with a diagnosis of rectal Cancer stage 1, condition after surgical treatment in 2000. Relapse in the perineum, the germination of posterior wall of vagina. Colportage. Anemia 2 tbsp.
When inspecting the vagina stenotic to the middle third malopopuljarnyh tumor, bleeding profusely at the contact.
The treatment by the proposed method with a positive effect bleeding stopped, achieved partial regression of tumors (multiplicity reduction 2.4). The patient is alive at the present time, within 8 months after the diagnosis of recurrence, with no signs of bleeding from the vagina, recto-vaginal fistula.
The proposed method helps to prolong life and improve its quality at heavy contingent of patients, almost not subject to regulations anticancer treatment.
The method of treatment of cancer patients with neoplastic lesions of the vagina, including chemoradiation therapy with cytostatic, remote and intracavitary irradiation, characterized in that for the first 3 or 6 days depending on the distribution of tumor Parag is of spend only a monochemotherapy, for the introduction of cytostatic apply the applique cloth Collex" entered PROXIFIER and methylsulfoxide when the mass ratio of 4.5 to 5.0:0.5 to 1.5, respectively, with a napkin pre-advanced moisten 20%solution of dimethyl sulfoxide and fixed by means of tight tamponade vagina, change cloths are produced every 24 hours, with 4 or 7 nights at the same time with applique conduct contact radiation sources of high activity GENUS 2 Gy and remote radiation exposure after 4-6 h on the pelvis GENUS 2G 10 sessions, 5 times a week.
FIELD: medicine, in particular angiogenesis prophylaxis and treatment.
SUBSTANCE: invention relates to 2-cyclooxygenase inhibitors selected from group containing 4-[5-(4-chlorophenyl)-3-phenyl-1H-pyrazole-1-yl] benzenesulfonamide; 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzenesulfonamide; 4-[5-methyl-3-phenyloxazole-4-yl] benzenesulfonamide or pharmaceutically acceptable salts thereof and pharmaceutical composition containing the same in therapeutically effective amount. Said composition are useful in treatment and/or prophylaxis of angiogenesis disorders such as metastasis, eye angiogenesis, diabetic retinopathy, etc. in subjects are needed in such treatment and/or prophylaxis.
EFFECT: new pharmaceuticals for angiogenesis treatment and/or prophylaxis.
SUBSTANCE: method involves introducing antitumor chemo preparations with blood components. To do it, 300 ml of patient autoblood is subjected to centrifuging during 20 min at 2200 rpm. The produced 150-200 ml of autoplasma and 100 ml of packed red blood cells are placed into separate reservoirs. Cys-platinum as single dose of 100 mg is incubated with the autoplasma and cyclophosphane as single dose of 1 g is incubated with the packed red blood cells. Single doxorubicin dose of 30-50 mg is concurrently introduced with one of the preparations. When combined with cis-platinum, doxorubicin is incubated with the packed red blood cells. When combined with cyclophosphane, doxorubicin is incubated with the autoplasma. Reinfusion is carried out to bring total dose of the preparations to 150 mg of doxorubicin, 3-5 g of cyclophosphane and 200 mg of cis-platinum. Pause between the procedures is 3-4 days long.
EFFECT: avoided risk of adverse side effects; increased preparation activity; accelerated treatment course.
SUBSTANCE: method involves making experimental animal temperature increase by infecting it with spotted fever after having removed the main tumor. The temperature is to be increased to the level causing tumor cells destruction. The temperature is supported for 4-6 h and typhus treatment is started.
EFFECT: enhanced effectiveness of treatment; inhibited metastases development.
FIELD: organic chemistry, medicine, oncology, pharmacology.
SUBSTANCE: invention relates to a composition used in treatment of proliferative diseases and comprising the platinum coordinating complex with an anti-tumor agent and derivative of pentafluorobenzene sulfonamide. Also, invention relates to a method for treatment by using the indicated composition. The composition possesses the synergetic effect.
EFFECT: improved and valuable method of therapy.
13 cl, 5 dwg, 1 ex
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to lyophilized composition comprising epotilone in the effective amount and mannitol or cyclodextrin. The second variant of the lyophilized composition involves epotilone and hydroxypropyl-beta-cyclodextrin. The preferable content of epotilone in the lyophilized composition is from 0.1% to 1.5%, and cyclodextrin - from 90% to 99% as measured for the total mass of solid components. Epotilone-containing lyophilized compositions can be used fro preparing an anti-tumor medicinal agent useful for parenteral administration and the lyophilized composition can be reduced preferably before administration directly. Epotilone-containing lyophilized compositions show improved indices of epotilone solubility and can retain stability for 24-36 months at temperature from 2°C to 30°C being without change of the solubility index.
EFFECT: improved and valuable properties of composition.
10 cl, 4 tbl, 14 ex
FIELD: medicine, chemical-pharmaceutical industry, pharmacy.
SUBSTANCE: invention relates to using 4-chloro-2-methylphenoxyacetic acid of the formula (I)
and its pharmacologically acceptable sodium, potassium and lithium salts (mixture of these salts, or mixture of salts and 4-chloro-2-methylphenoxyacetic acid) as a medicinal agent possessing immunomodulating, anti-inflammatory and antitumor properties, and antiviral activity also. 4-Chloro-2-methylphenoxyacetic acid and its mixtures with pharmacologically acceptable alkaline metal salts possess high effectiveness and enhanced bioavailability.
EFFECT: valuable medicinal properties of medicinal agent.
9 cl, 13 ex
FIELD: chemistry of peptides, medicine.
SUBSTANCE: invention relates to preparing new peptides possessing immunomodulating, anti-proliferative, anti-tumor and antiviral activity. Invention proposes new peptides comprising up to 30 amino acid residues of the general structural formula: X1-Trp-Gly-Gln-X2 wherein X1 is taken among the following group: -His-Gly-Val-Ser-Gly-, -His-Gly-Gly-Gly-, -His-Val-Gly-Gly-, -His-Gly-Gly-Gly-Gly-, and -Gln-Gly-Gly-Gly-Gly, or absent; X2 is taken among the following group: -His-Gly-Thr-His-Gly, -Gly-Gly-Thr-His-Gly, -Pro-His-Val-Gly-Gly, -Pro-His-Gly-Gly-Gly, -Pro-His-Gly-Gly-Gly-Trp-Gly, -Gly-Gly-Gly-Thr-His-Ser, or absent.
EFFECT: valuable medicinal properties of peptides.
8 cl, 5 tbl, 5 dwg, 6 ex
FIELD: organic chemistry, medicine, oncology, pharmacy.
SUBSTANCE: invention relates to new derivatives of quinazoline of the formula (I):
wherein m = 0, 1, 2 or 3; each group R1 that can be similar or different is taken among halogen atom, trifluoromethyl, hydroxy-, amino-group, (C1-C6)-alkyl, (C2-C8)-alkenyl, (C2-C8)-alkynyl, (C1-C6)-alkoxy-, (C2-C6)-alkenyloxy-, (C2-C6)-alkynyloxy-, (C1-C6)-alkylamino-, di-[(C1-C6)-alkyl]amino- and (C2-C6)-alkanoylamino-group, or among the group of the formula: Q1-X1- wherein X1 represents oxygen atom (O); Q1 represents aryl-(C1-C6)-alkyl, heteroaryl, heteroaryl-(C1-C6)-alkyl, heterocyclyl or heterocyclyl-(C1-C6)-alkyl and wherein neighboring carbon atoms in any (C2-C6)-alkylene chain in substitute at R1 are separated optionally by insertion to the chain the group taken among oxygen atom (O) and N(R5) wherein R5 represents hydrogen atom or (C1-C6)-alkyl, or when the inserted group represents N(R5); R5 can represent also (C2-C6)-alkanoyl and wherein any group -CH2 or -CH3 in substitute R1 carries one or more substitutes in each indicated group -CH2 or -CH3 and wherein these substitutes are taken among halogen atom or (C1-C6)-alkyl, or substitute taken among hydroxy-, amino-group, (C1-C6)-alkoxy-, (C1-C6)-alkylthio-group, (C1-C6)-alkylsulfinyl, (C1-C6)-alkylsulfonyl, (C1-C6)-alkylamino-, di-[(C1-C6)-alkyl]amino-, (C2-C6)-alkanoyloxy, (C2-C6)-alkanoylamino- and N-(C1-C6)-alktyl-(C2-C6)-alkanoylamino-group, or among the group of the formula: -X3-Q3wherein X3 represents oxygen atom (O) and Q3 represents heteroaryl, and wherein any aryl, heteroaryl or heterocyclyl group in substitute at R1 carries optionally 1, 2 or 3 substitutes that can be similar or different and taken among halogen atom, trifluoromethyl, cyano-, hydroxy-, amino-group, carbamoyl, (C1-C6)-alkyl, (C2-C8)-alkenyl, (C2-C8)-alkynyl, (C1-C6)-alkoxy-, (C2-C6)-alkenyloxy, (C2-C6)-alkynyloxy,(C1-C6)-alkylthio-group, (C1-C)-alkylsulfinyl, (C1-C6)-alkylsulfonyl, (C1-C6)-alkylamino-, di-[(C1-C6)-alkyl]amino-group, (C1-C6)-alkoxycarbonyl, N-(C1-C6)-alkylcarbamoyl, N,N-di-[(C1-C6)-alkyl]carbamoyl, (C2-C6)-alkanoyl, (C2-C6)-alkanoyloxy-, (C2-C)-alkanoylamino- and N-(C1-C6)-alkyl-(C2-C6)-alkanoylamino-group, or among the group of the formula: -X4-R8 wherein X4 represents a simple bond and R8 represents hydroxy-(C1-C6)-alkyl, (C1-C6)-alkoxy-(C1-C6)-alkyl, cyano-(C1-C6)-alkyl, amino-(C1-C6)-alkyl, (C1-C6)-alkylamino-(C1-C6)-alkyl or di-[(C1-C6)-alkyl]amino-(C1-C6)-alkyl, or among the group of the formula: -X5-Q4 wherein X5 represents a simple bond or -CO, and Q4 represents heterocyclyl or heterocyclyl-(C1-C6)-alkyl that carries optionally 1 or 2 substitutes that can be similar or different and taken among halogen atom, (C1-C6)-alkyl, (C2-C8)-alkenyl, (C2-C8)-alkynyl and (C1-C6)-alkoxy-group and wherein any heterocyclyl group in substitute at R1 carries optionally 1 or 2 oxo-substitutes, and wherein any aryl group in the group R1 represents phenyl; any heteroaryl group in the group R1 is taken among pyrrolyl, imidazolyl, triazolyl and pyridyl, and any heterocyclyl group in the group R1 is taken among oxyranyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, morpholinyl, 1,1-dioxotetrahydro-1,4-thiazinyl, piperidinyl, homopiperidinyl, piperazinyl and homopiperazinyl; R2 represents hydrogen atom; n = 0, 1, 2 or 3; R3 represents halogen atom, trifluoromethyl, cyano-, hydroxy-group, (C1-C6)-alkyl, (C2-C8)-alkenyl, (C2-C8)-alkynyl or (C1-C6)-alkoxy-group, or its pharmaceutically acceptable salt. Also, invention relates to methods for preparing compounds of the formula (1) and to pharmaceutical composition based on thereof for using as an anti-tumor agent. Invention provides preparing new derivatives of quinazoline possessing an anti-tumor activity.
EFFECT: improved preparing method, valuable medicinal properties of compounds and pharmaceutical composition.
17 cl, 7 tbl, 7 ex
FIELD: organic chemistry, medicine, oncology, pharmacy.
SUBSTANCE: invention relates to new derivatives of acridine of the formula (1):
wherein R, R1, R2 and R3 mean hydrogen atom; Z means oxygen or sulfur atom; X means nitrogen atom or C-R5 wherein R5 means hydrogen atom; n = 2; m = 0; R4 means (C1-C3)-alkyl residue that can be substituted with aryl, (C4-C10)-heteroaryl and other substitutes, (C6-C10)-aryl and others, and to their pharmaceutically acceptable salts. Compounds of the formula (1) possess an anti-tumor activity and can be used as an active component of the medicinal agent.
EFFECT: improved preparing method, valuable medicinal properties of compounds and composition.
9 cl, 1 tbl, 20 ex
SUBSTANCE: method involves combining vaccine prepared from 107 cells of autologic tumor lysate with 60 mg of betaleukine and introducing it strictly in intracutaneous paravertebral mode in three points arranged 3 cm far from each other. The introduction takes place every 3 weeks so that the first two vaccinations are combined with 470 mg of betaleukine introduced into anterior abdominal wall. Vaccination treatment is continued on receiving positive retarded type hypersensitivity response to injection after every vaccination with tumor lysate without betaleukine.
EFFECT: enhanced effectiveness in inducing and supporting antitumor immune response.
SUBSTANCE: invention is directed, in particular, to treatment of patients with Ewing's sarcoma and osteogenic sarcoma at different stages of malignant process. Method comprises chemotherapy and beam therapy. Samples of venous blood are taken from children in age of 5 to 12 years in amounts not larger than 5% of the total volume of circulating blood per 1 introduced dose of chemical preparation and, from adolescents and young persons, in amount of 200 ml. Then 4 courses of polychemotherapy are fulfilled with autoblood according to standard treatment schemes for given diseases, taking into account stages of disease, in recommended doses. Between 2nd and 3rd chemotherapy courses, radiotherapy is fulfilled on metastatic focuses in lungs. After 4 courses of induction autohemo-chemotherapy, local therapy on the primary focus (radiotherapy and/or surgical treatment) is fulfilled and also radiotherapy on metastatic focuses in other bones, after which follows consolidation involving chemical preparation of the second line.
EFFECT: improved remote results of treatment , suppressed metastatic focuses, reduced tumor dimensions, and weakened toxic manifestations of therapy.
SUBSTANCE: the present innovation deals with measuring radioactivity in alive organisms and could be applied for detecting really absorbed dosage under conditions of intra-operational impact. The method suggested includes detecting clinical volume for the target of radiation impact including the volume of healthy tissues to be subjected for radiation impact, developing the plan of radiation impact based upon data obtained with the help of tissue-equivalent phantoms, location in interest sites of clinical volume of sterilized separate fragments of dosimetric device being the matrix of functional units and designed as thermoluminescent detectors being hermetically isolated at the distance of 10 mm between their edges and fixed between the layers of flexible biocompatible material, registering the location of detectors, performing the séance for intra-operational radiation therapy followed by removing the fragments of dosimetric device out of target's volume. Information should be read from thermoluminescent detectors.
EFFECT: higher accuracy of measuring.
1 cl, 1 dwg, 1 ex
SUBSTANCE: the present innovation deals with treating malignant tumors of central bronchi and trachea due to argonoplasmatic recanalization of tracheal lumen and/or bronchi, at power being 60-90 W followed by brachitherapy at source's trajectory length being 5-20 cm, pace of 5 mm and the depth of reference isodose being 10 mm against the source. Moreover, one should move applicator above and below the tumor ranged 1-3 cm to apply the dose ranged 14-28 Gy once weekly per 7 Gy. Additionally, one should carry out distance radiation therapy 5 times weekly per 1-2 Gy up to total focal dose of 30-40 Gy. The present innovation enables to highly increase the passability of respiratory tract in case of malignant stenosis and prevent the development of their relapse.
EFFECT: higher efficiency of therapy.
FIELD: medicine, neurooncology.
SUBSTANCE: one should carry out chemotherapy and irradiation till radical dosage. Moreover, 2-3 d before the onset of radiation therapy and during the whole course of irradiation one should indicate the intake of indometacin at daily dosage being 300 mg, and 8-14 d before the end of therapy course or the stage of radiation therapy it is necessary to conduct chemotherapeutic cycle with vincristine at total dosage being 4 mG and lomustine at total dosage 160-240 mg. At performing a split course of irradiation the intake of indometacin should be indicated between the stages. The innovation enables to increase radio sensitivity of malignant tumor, suppress angiogenesis, proliferative activity and increased cytotoxic activity of chemopreparations.
EFFECT: higher efficiency of therapy.
1 cl, 3 ex
FIELD: medicine, oncology, gynecology.
SUBSTANCE: method involves external irradiation and using chemopreparations combined with autoplasma. External irradiation in the dose 2 Gr is carried out from 1 to 4 day of treatment followed by intravenous administration of cisplatin on 5 day in the dose 10 mg with 250 ml of physiological solution. On the following day 10 ml of autoplasma incubated with 10 mg of cisplatin is administrated by paratumoral route by right and left of tumor into paravaginal cellular tissue and by intratumoral route into projection of cervical channel. Blood cellular elements are incubated with 600 mg of cyclophosphane and reinfused by intravenous drop route. Effects are repeated in indicated sequence once per a week, 4 times per treatment course. Method provides increasing percent of tumor regression due to the complex effect on tumor, enhancing the topical concentration of cytostatic drug and prolongation of its contact in malignant growth zone, and providing radiosensibilizing effect in diminishing the general toxic effect of therapy. Invention can be used in treatment of patients with topically disseminated forms of uterus cervix cancer at the stage T3NxM0.
EFFECT: improved and enhanced treatment method.
FIELD: medicine, oncourology.
SUBSTANCE: the present innovation deals with conservative treatment of patients with malignant prostatic tumor at different stages. The method includes testicular enucleation, introduction of anti-tumor chemopreparations and radiation therapy. Moreover, in the onset of radiation therapy one should introduce 25 mg Cisplatin incubated with 10 ml patient's plasma into both prostatic lobes and paraprostatic fiber from the right and from the left. At achieving a focal dosage of 20 Gy one should repeat introduction of chemopreparation in similar dosage, and radiation therapy should be continued up to total focal dosage of 40 Gy. The innovation enables to decrease tumor sizes, side manifestations of radiation therapy at decreasing radiation loading and improve patient's life quality due to mitigating the urination.
EFFECT: higher efficiency of therapy.
FIELD: medicine, oncology.
SUBSTANCE: before irradiation it is necessary to cool the tumor to achieve the temperature of freezing at clinically detectable border between the tumor and healthy tissue to perform irradiation directly after natural tissue defrosting with a single focal dosage (SFD) being 2-2.5 Gy daily for 5 d a week at 2-d-long interval to achieve total focal dosage (TFD) of 60-65 Gy. Moreover, the area of healthy tissue should be protected with a shielding applicator - a lead plate - during irradiation. The present innovation enables to maximally keep anatomical relief and function of local tissues.
EFFECT: higher efficiency of therapy.
1 cl, 4 ex
FIELD: medicine, oncology.
SUBSTANCE: the method deals with applying chemopreparations incubated with autolymph and radiation therapy. Lymph taken out of patient's thoracic duct should be centrifuged for 30 min at 2200 rot./min, lymphatic plasma should be taken and frozen at -40 C, lymphatic formic elements should be incubated in a thermostat at 37 C for 1 h together with chemopreparations by a certain scheme to be reinfused for a patient intravenously by drops according to the given scheme. Then, 2 wk later, one should perform therapy with a split course of distance gammatherapy at single focal dosage (SFD) of 4 Gy. At the first stage one should apply per 2 Gy twice daily at 4-5-h-long interval 5 times weekly, at achieving focal dosage of 28 Gy it is necessary to have a week-long interval. Then radiation therapy should be continued but SFD of 4 Gy should be applied at once. One should fulfill 3 fractions of irradiation per a week, there are 6 fractions during the second stage, totally. Total focal dosage (TFD) per the whole course of irradiation corresponds to 52 Gy. About 4 wk after radiation therapy one should defrost lymphatic plasma to incubate it with the same chemopreparations in a thermostat at 37 C for 1 h to be then reinfused for a patient intravenously by drops. The method enables to decrease tumor volume and tumor process metastasing without any operative interference.
EFFECT: higher efficiency of therapy.
FIELD: experimental medicine, oncology, biology.
SUBSTANCE: invention relates to a method for inhibition of tumor growth using radiation therapy as ionizing radiation with additional administration of mixture of octa-4,5-carboxyphthalocyanine sodium cobalt salt or oxocobalamine with sodium ascorbate in the ratio = (1:10)-(1:30). Method of combined using irradiation and indicated mixture of substances provides enhancing the effectiveness of anti-tumor treatment resulting to 70-100% recovery of experimental animals and reducing radiation loading and toxicity.
EFFECT: improved method for inhibition.
2 tbl, 3 dwg, 3 ex
SUBSTANCE: the method deals with 2 courses of polychemotherapy at the first stage due to regional intra-arterial introduction of cisplatin at the dosage of 100 mg/m2 during the first day of every course and 6-h-long intra-arterial infusion of 5-fluorouracil at total dose of 750 mg/m2 in the morning since the 2nd to the 6th d of every course. Chemotherapy should be performed at the background of total magnetotherapy at frequency of magnetic field being 98-112 Hz, intensity of 25-30 oersted, duration of every seance being 30 min, the number of seances corresponds to the duration of chemotherapeutic courses. At the second stage in 2-3 wk after finishing chemotherapy it is necessary to conduct the course of distance radiation therapy (DRT) at multifractioning the dosage by SFD being 1.2 Gy twice daily 5 times weekly up to TFD being equivalent to TDF (time-dosage-fraction) of 62-70 Gy onto primary focus and 40-46 Gy onto areas of regional lymph outflow. As modifiers one should apply cisplatin during the first 2 wk of radiation therapy, hyperbaric oxygenation during the first 10 d of radiation therapy and total magnetotherapy since the 11th d of DRT course till its ending. At the third stage in case of residual metastases in lymph nodes of patient's neck in 2-3 wk after the end of radiation therapy one should conduct operative interference in lymph outflow pathways. The method enables to decrease toxicity of chemo-and radiation therapy due to decreased radiation reactions, stimulation of immune system and improved microcirculation.
EFFECT: higher efficiency of therapy.
FIELD: medicine, gerontology.
SUBSTANCE: the present innovation deals with rehabilitation therapy of cerebrovascular diseases. One should introduce microcirculators and nootropic preparations to conduct training neuropsychological procedures. Moreover, microcirculatory and nootropic preparations should be introduced as intravenous infusions for 10 d, ten during 1 mo it is necessary to introduce tableted forms of the same preparations at simultaneous neuropsychological training directed to improving household skills valuable for a patient that deal with memorizing different names, important dates, names of medicinal preparations and location of domestic articles. On achieving a success the tasks should be complicated. Training should last for 30 min carried out thrice weekly: therapy course includes 12 trainings. The innovation widens the number of preparations for treating elderly and senile patients at discirculatory encephalopathy stage III and coarse cognitive deficiency.
EFFECT: higher efficiency of therapy.
3 ex, 1 tbl