RU2145217C1 - Method of tumor radiosensibilization - Google Patents

Abstract

FIELD: medicine, oncology. SUBSTANCE: invention relates to treatment of patients with malignant neoplasms of lung, tumors of upper respiratory ways, uterus and straight intestine. Invention proposes administration of radiosensibilizing medicinal mixture to patients with disorders of regionally circulation 0.5-1.0 h before radiation therapy by endobronchial, intravaginal, intrarectal, intralarynx routes. Mixture has 0.05-1.0 g of diprophylline and 0.001-0.005 g of partusisten as radiosensibilizing agents that is administrated by infusion. EFFECT: enhanced tumor resorption. 3 ex

Description

 The invention relates to medicine, more specifically to radiation therapy of malignant neoplasms, and can be used in remote radiation therapy of lung cancer, tumors of the upper respiratory tract, uterus and rectum.

A known method of treating malignant tumors (copyright certificate N 137697 from 08.10.87, IPC ⁶ A 61 N 5/00), including radiosensitization of the tumor during radiation therapy of lung cancer, which involves either intravenous administration of 10 - 15 ml of 2.4% - a solution of aminophylline, or intramuscular injection of 1.5 - 2.5 ml of a 0.05% solution of alupent 2 to 3 hours before irradiation, which is carried out in single doses of 1.8 - 2.5 Gy five days a week until the total dose 30 - 40 Gy However, the known method does not provide radiosensitization of a lung tumor, when, due to the germination and compression of the blood vessels of the tumor supplying the tumor, the radiosensitizers cannot penetrate the tumor cells through the bloodstream.

There is a method of treating lung cancer (copyright certificate N 1522502 from 07.15.89, IPC ⁶ A 61 N 5/00), we have chosen as a prototype, which provides for the inhalation of a radiosensitizing mixture of the following composition: 1.0 - 2.0 ml 12 - 24% solution of aminophylline, 0.5 - 1.5 ml of a 0.05% solution of alupent and 1.0 - 2.0 ml of dimexide when the temperature of the inhalation mixture is 19 - 37 ^o C. After 1 - 2 hours after inhalation aerosols of radiosensitizing mixtures carry out radiation therapy in a movable pendulum mode or multi-field method 5 times a week the absorbed dose per session is 1.8 - 2.5 Gy, the total absorbed dose is 40 - 50 Gy.

 However, this method does not provide radiosensitization of the lung tumor during radiation therapy, when the patient, along with severe circulatory disorders in the lung affected by the tumor, has gross bronchial obstruction, i.e. when the radiosensitizer cannot be brought to the tumor either through the bloodstream or by aerosol inhalation.

 The aim of the invention is to enhance tumor resorption during radiation therapy of radioresistant forms of cancer of the lung, larynx, cervix and rectum with severe impairment of regional blood flow.

 The goal is achieved in that 0.5 to 1.0 hours before the radiation therapy session, 3.0 to 5.0 ml of a mixture of medicinal substances containing 0.05 - is poured into the patient with endobronchial discrete portions of 0.3 - 0.5 ml. 0.1 g of diprofillin and 0.0005 - 0.005 g of partusisten and 1.0 ml of dimexide. The radiosensitizing mixture is delivered to the tumor (into the lumen of the bronchus or larynx, vagina, cervical cavity or rectum) using a device for administering a drug substance (Patent N 2019194, Bull. No. 17 dated 09.15.94). Thus, in contrast to the prototype, in the proposed method, radiosensitizers (diprofillin and partusisten) with a solvent (dimexide) are brought to the tumor by the method of endobronchial (intracranial, intravaginal, intrathecal) infusion in discrete portions of 0.3 - 0.5 ml, carried out using devices for administering a drug substance.

 The invention - a method of radiosensitization of a tumor - is new, since it is not known from the level of medicine in the field of radiation therapy of malignant neoplasms. The novelty of the invention lies in the fact that when a patient, along with circulatory disorders in a tumor affected organ, such as a lung, gross bronchial obstruction is observed (due to endobronchial tumor growth or compression during rebronchial-nodular form of lung cancer), which makes it impossible to bring to the tumor medicinal substances neither in the bloodstream, nor in the form of an aerosol, or in case of laryngeal cancer, cervical cancer, or rectal cancer, 0.5 to 1.0 hours before the radiation therapy session, the patient is poured into the cavity with Resp body mixture of solution and diprofillina partusistena that act as radiosensitizers selectively enhancing radiation sensitivity of tumor cells in combination with a universal aprotic solvent - Dimexidum which enhances the diffusion of drugs into tumor cells increases their concentration in the tumor.

 Unlike the known methods of introducing radiosensitizers, diprofillin and partusisten with a solvent of dimexide are delivered to the tumor by endobronchial or intracavitary infusion using a device approved by VNIIGPE (patent N 2019194 from 09.15.94). This device provides an infusion of drugs when radiosensitizers cannot be brought to the tumor either through the bloodstream or in the form of aerosol inhalation. Thus, there is an increase in tumor resorption and an increase in the survival of patients with radiation therapy of radioresistant forms of cancer of the lung, larynx, cervix, and rectum with severe disturbances in regional blood flow.

 The proposed method for radiosensitization of tumors has an inventive step, since the use of diprofillin and partusisten as radiosensitizers in radiation treatment of malignant tumors is not known from the level of medicine and there is no description of the local administration of these drugs in the available medical literature.

 The invention is industrially applicable, since it can be used in healthcare in oncological institutions and research institutes of the Russian Federation for remote radiation therapy of lung cancer, tumors of the upper respiratory tract, cervix and rectum.

 Examples of specific performance of the "Method of radiosensitization of tumors."

 The method is as follows: 0.5 to 1.0 hours before a radiation therapy session to a patient using a device for administering drugs, endobronchial discrete portions of 0.3 to 0.5 ml are poured into a mixture containing 0.1 - 0.25 g diprofillin, 0.005-0.0005 g of partusisten and 1.5-2.5 ml of dimexide. After 0.5 - 1.0 h after the infusion of the radiosensitizing mixture, an external exposure session is carried out on a gamma therapeutic unit or a medical accelerator, either by pendulum swing or by multi-field method with average fractionation of 4 - 5 Gy twice a week, the total focal dose is 40 - 48 gr

 Patient N., 59 years old, was admitted to the radiology department of the Rostov Cancer Research Institute with a diagnosis of central cancer of the left lung, peribronchial-nodular form with lesions of the lower lobe and intermediate bronchus, art. 3, class. column 2. On roentgenograms and tomograms of the chest in the left lung, the tumor node is pounded into the root, emanating from the lower lobe bronchus, the intermediate bronchus in the lower section ends with a stump. When bronchoscopic examination, a narrowing of the lumen of the intermediate bronchus in the form of a gap is noted on the left, the mucous membrane is infiltrated, friable. Histological analysis N 157344 - squamous cell carcinoma with keratinization. Data from a radionuclide study of alveolar ventilation (ventilation index in the left lung is 24) indicates a decrease in the function of external respiration in the tumor affected lung, mainly in the lower lobe. Capillary blood flow (perfusion index equal to 24) is also significantly reduced in the left lung. The patient underwent radiation therapy on the Agat-R equipment in a mobile pendulum mode with an average fractionation of 5 Gy twice a week, the total absorbed dose was 40 Gy. 30 minutes before the radiation therapy session, an endobronchial infusion of a radiosensitizing mixture was carried out, including 0.1 g of diprofillin, 0.005 g of partusisten and 1.0 - 2.5 ml of dimexide. Infusion was carried out in discrete portions using a device for the introduction of medicinal substances. After the treatment, the tumor node is not determined on radiographs and tomograms, bronchial lumens are free. During bronchoscopic examination, a restoration of patency of the bronchi of the left lung was noted; no tumor cells were found in smears from bronchi.

 Patient K., 64 years old, was admitted to the radiology department with a diagnosis of central cancer of the right lung with damage to the intermediate and main bronchi, art. 3., class. column 2. On radiographs and tomograms, a tumor node measuring 5 x 7 cm, enveloping the main and intermediate bronchi, is detected. The lumen of the main bronchus is narrowed, the intermediate bronchus ends with a stump. Pneumatization of the lower lobe is sharply reduced.

 When bronchoscopic examination revealed a narrowing of the lumen of the main bronchus, the lumen of the intermediate bronchus is obstructed by a tumor. Tumor biopsy was performed, histological conclusion - adenocarcinoma. Data from a radionuclide study of alveolar ventilation (ventilation index is 17%), lung capacity, total lung capacity, functional residual lung capacity indicate a decrease in external respiration function in the entire right lung, mainly in the lower lobe. The ratio of ventilation to blood flow is significantly higher than 1.0, and capillary blood flow (perfusion index is 12%) is sharply reduced, especially in the lower lobe, which also confirms a significant violation of regional blood flow in the right lung.

 The patient underwent radiation therapy on the Rokus apparatus in a movable pendulum mode, with an average fractionation of 4 Gy twice a week, the total absorbed dose of 48 Gy. 1 hour before the radiation therapy session with the device for drug administration, endobronchial infusion was carried out in discrete portions of a radiosensitizing mixture, including 2.5 ml of a 10% solution of diprofillin, 2.0 ml of a 0.005% solution of partusisten and 2.5 ml of dimexide .

 After the treatment, the tumor node is not determined on radiographs and tomograms, bronchial lumens are free. During bronchoscopic examination, there was a restoration of patency of the bronchi of the right lung; no tumor cells were found in smears from bronchi.

 Patient H, 38 years old, was admitted to the radiology department of the RNII on 06.19.95 with a diagnosis of cervical cancer, art. column 2, a.a. squamous cell carcinoma with keratinization in a state of moderate severity with bleeding from the genital tract and posthemorrhagic anemia. When viewed in the mirrors, the vagina is capacious, made up to the border of the middle and lower third of a decaying exophytic tumor with a crater in the center, vault infiltration, P.V. - P.R .: the uterus is usually located somewhat increased in size due to the neck, the appendages are not determined, in the parameters the infiltration is moderate on the left, on the right - to the pelvic wall. In connection with bleeding with hemostatic purpose, the patient was urgently taken to an intracavitary radiation session. The bleeding was stopped. After that, remote radiation therapy was performed on the Rocus-M apparatus from two opposite curly fields, SOD to point A - 20 Gy, to point B - 46 Gy. 1 h before the radiation therapy session after the vaginal toilet, a radiosensitizing mixture was introduced into the posterior fornix, including 0.1 g of diprofillin, 0.005 g of partusisten and 1.0 ml of dimexide. After remote radiation therapy, a positive effect was achieved, expressed in a complete regression of exophyte and cleaning the cervix and vagina from necrotic masses.

 Status genitalis after treatment: the vagina is narrowed in the upper third, the cervix is formed, mild epithelitis.

 Patient L. was admitted to the radiology department with a diagnosis of colorectal cancer, the condition after extirpation of the rectum, relapse with germination of the posterior wall of the vagina. Upon admission, the vagina is blind, at a distance of 5-6 cm from the introitus along the posterior wall, the tumor is 6 x 8 x 3 cm in size with disintegration, contact bleeds, the neck and appendages without features, remote radiation therapy was performed on the pelvic tumor, before each radiation session of therapy after the vaginal toilet, a radiosensitizing mixture consisting of 0.1 diprofillin, 0.005 g partusisten and 1.0 ml of dimexide was injected into the posterior arch, the total focal dose was 44 Gy, then intracavitary radiation therapy was carried out against the background of preliminary administration of p adiosensitizing mixture, the total focal dose is 30 Gy. After the treatment: the vagina is capacious, the cervix is clean, in the posterior fornix epithelitis, a seal of 1.5 x 2.0 x 0.5 cm is palpated.

 The technical and economic efficiency of the "method of radiosensitization of the tumor" lies in the fact that the use of the method allows to enhance the resorption of the tumor in patients with cancer of the lung or cervix in cases where the radiosensitizers cannot be brought to the tumor through the bloodstream, or in the form of aerosol inhalation by a patient with lung cancer.

Claims (1)

 A method of radiosensitization of a tumor, comprising bringing the radiosensitizing mixture directly to the tumor into the cavity of the organ affected by the tumor with subsequent radiation therapy, characterized in that if the regional blood flow is disturbed 0.5 to 1.0 hours before the radiation therapy session, endobronchial discrete portions, or intra-throat discrete a radiosensitizing mixture is added in portions, either intravaginally or intradermally, including 1.0 - 2.5 ml of a 10% diprofillin solution and 2.0 - 3.0 ml of a 0.005% partusisten solution with the addition of m 1.5 - 2.5 ml of dimexide.