Method of post-surgical treatment of cerebral tumour

FIELD: medicine.

SUBSTANCE: for the purpose of post-surgical treatment of cerebral tumours, memantine is prescribed in a dose of 10 mg daily for 5-7 days before radiation therapy, and in a dose of 20 mg during radiation therapy 4-6 hours before the radiation session. On completing the course of radiation therapy, memantine is prescribed in patients aged up to 60 years old in a dose of 10 mg for 2-3 months daily, in patients aged 60 and older in a dose of 20 mg for 5-6 months daily.

EFFECT: method enables providing the higher patients' quality of life with a view to cancellation of glucocorticoids, ensuring higher clinical effectiveness ensured by an increase of the medullary substance to radiation.

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The invention relates to medicine and can be used in the treatment of patients with brain tumor.

Malignant brain tumors are the most frequently diagnosed cancer of the Central nervous system. Standard treatment for these tumors is surgical removal of the tumor followed by adjuvant radiotherapy in standard mode fractionation of the dose of irradiation to a total dose of 60 Gy. Local recurrence after treatment occurs, usually 12-14 months. It is believed that the reason for such an early relapse is the lack of technical capacity total removal of the tumor due to the fact that it has no clear boundaries with the surrounding intact the substance of the brain or its localization in the area of vital centers of the nervous system, limiting surgical activity. No less important cause of relapse is high radioresistance of residual tumor, irradiation in the dose of 60 Gy leads to only sublethal damage to its forming cells. The increase in the number of fatal injuries is possible only by increasing the total dose of radiation more than 60 Gy or a single dose of irradiation. But the use of such aggressive treatment inevitably leads the children to the damage of the brain, entering the target irradiation, which in itself can cause death of the patient. In order to reduce the negative impact of irradiation on the substance of the brain are used glucocorticoids, however, causing a number of serious side effects, such treatment may exacerbate the already precarious condition of the patient. In some cases, such as patients with diabetes, the use of glucocorticoids is impossible, which casts doubt on the feasibility of adjuvant radiation therapy in these patients and dooms them to a premature death.

There is a method of treatment of malignant brain tumors, when during adjuvant radiation therapy the patient is prescribed the introduction of corticosteroids to reduce brain edema resulting from radiation damage to the elements of the microvasculature of the brain (Cancer Res Treat. -2006. - V.128. - P.7-22. Shaw EG, Robbins, M.E.).

The disadvantage of this method are profound metabolic disturbances in the body of the patient in response to the introduction of glucocorticoids, which significantly impairs the physical condition of patients, the cause of sleeplessness, depression and in some cases is the cause of interruption of the course of radiation therapy. All this negatively affects the comfort and life expectancy of such patients. Given the initial method of treatment cannot be applied in patients with diabetes, since the introduction of glucocorticoids lead to decompensation of diabetes mellitus, and instead of reducing the damaging effects of irradiation on the brain caused the opposite effect - the degree of radiation damage of blood vessels in patients with diabetes mellitus on the background of the introduction of glucocorticoids increased, which caused the development of radiation necrosis and death of patients.

Closest to the claimed is a method of treatment of malignant brain tumors (RF Patent No. 2143893, IPC AC 31/17, publ. 2000), including a course of radiation and drug therapy involving before and during adjuvant radiotherapy for patients with malignant brain tumor assign a blocker of the calcium receptor. Chemotherapy is drug microsociety.

The disadvantages of this method is that the use of a blocker of the calcium receptor is limited in elderly patients with concomitant cardiac pathology, and, as shown in statistics, older patients among those who need adjuvant radiation therapy in connection with a brain tumor the majority. Blocker calcium receptor acts mainly at the level of the vascular wall brain, while radiation damage occur in the vascular wall and the cellular elements and the article is ome matter of the brain. Restricted use of the drug in violation of cerebral circulation, and among those patients who received surgical removal of the tumor, enough. The drug is terminated with the end of radiation therapy that is unreasonable from the point of view of the duration of radiation disease variability that occurs in the tumor, and the substance of the brain in response to irradiation.

The objective of the proposed method is to eliminate the above disadvantages, the efficiency of the treatment, reducing the radioresistance of residual tumor by increasing its oxygenation, reducing the damaging effects of radiation on the intact the substance of the brain by inactivation processes of peroxide oxidation, leading to oxidative stress, normalization of coagulation homeostasis in the brain, improving the efficiency of adjuvant radiation therapy by increasing pay and total doses, reducing timing of radiation therapy.

To solve the task during the course of radiation and drug therapy proposed as drug therapy to prescribe oral administration of memantine. 5-7 days before the beginning of radiation therapy prescribed for administration of memantine 10 mg daily during radiation therapy administered 20 mg for 4-6 hours before the session exposed the deposits. After radiation therapy patients under the age of 60 years shall receive of memantine 10 mg in 2-3 months daily, patients aged 60 years or more, appointed reception of memantine 20 mg for 5-6 months on a daily basis.

The occurrence of radiation damage of the microvasculature and cellular elements of the brain lead to greater degree of edema and hypoxia in the radiation zone, activation of anaerobic glycolysis followed by excessive release of glutamate and the violation of its reuptake. As a mediator excitation, glutamate causes prolonged stimulation of the cells, resulting in excessive entrance of calcium ions with subsequent release of proteases, which leads to accumulation in the cell of hydroperoxides, the development of oxidative stress and its destruction.

The above processes lead to spasm of cerebral vessels, platelet aggregation and the appearance of coagulation changes of hemostasis, which leads to increased hypoxia in the tumor and reduces the effectiveness of the treatment.

The purpose of memantine in patients whose planned adjuvant radiation therapy leads to normalization of blood-brain barrier permeability by suppressing the activity of P21, p38/MARK and reduce the degree of hypoxia of the brain, has an antioxidant EF is known, which leads to the rejection of the use of glucocorticoids, a more rapid recovery of brain functions are lost during surgical intervention, allows a shorter time to start exposure. On balance radioprotective properties of this drug in regard to the substance of the brain the opportunity to use more aggressive methods of radiation therapy, increasing as a single dose and total dose of radiation. Considering the fact that the processes of radiation-induced and causing oxidative stress, continue to operate after the termination of adjuvant radiation therapy, justified the admission of memantine at the stage of monitoring patients after completion of treatment. Moreover, it is essential that you should take into account the degree and depth of radiation damage, and these indicators are more pronounced in elderly patients. In this regard, the possibility to individually determine the dosage and timing of reception of memantine.

The implementation of the method is demonstrated on specific clinical examples.

Example 1.

Patient B., 50 years, performed surgical removal of a brain tumor. Histological examination showed that the tumor is a glioblastoma (malignant glioma 4 tbsp. PLN). In the postoperative period the patient about what was algal to complain of General weakness, right-sided hemiparesis, he noted cognitive disorders, dementia.

2 weeks after surgery scheduled memantine at a dose of 10 mg per day and cancelled dexamethasone. The patient's condition improved significantly, within 7 days after the start of treatment, memantine was appointed radiation therapy mode hypofractionation dose, which continued without interruption until the SOD=68 Gr.

During the entire course of radiation therapy the patient received memantine in daily doses of 20 mg, his condition remained stable, almost regressed symptoms of hemiparesis and dementia, recovered memory.

After completion of radiotherapy, the patient continued taking the memantine 10 mg per day. His health has remained satisfactory.

6 months after completion of radiation therapy on MRI in a patient not detected foci of damage to the substance of the brain and relapse.

Example 2.

Patient K., 63, uninstalled anaplastic astrocytomas (malignant glioma 3 tbsp. PLN). brain.

After the appointment of memantine in daily doses of 10 mg for 5 days, the patient is assigned to adjuvant radiation therapy, which was held in the classic mode fractionation of the radiation dose to 64 Gy. Throughout the course of therapy the patient received daily 20 mg of memantine. After C is the conclusion of adjuvant radiation therapy reception of memantine at a dose of 20 mg daily was continued and discontinued only after 6 months.

During the entire course of radiation therapy and 6-month follow-up period for the patients he needed no further introduction glucocorticoids, his condition remained satisfactory.

The proposed method of treatment was applied to 25 patients with different morphological forms of malignant brain tumors. Daily take of memantine in the recommended dosage before, during and after adjuvant radiation therapy was allowed in all cases, significantly improve the quality of life of patients due to the failure of the introduction of glucocorticoids and, as a consequence, the lack of patients the occurrence of deep metabolic disorders. In the course of adjuvant radiation therapy had no grounds to terminate the exposure. Reception of memantine resulted in improved cognitive brain function, memory, allowed patients to care for themselves without assistance.

The conduct of adjuvant radiation therapy in patients receiving antagonist extrasynaptic glutamate receptors of memantine on the proposed scheme can significantly increase the tolerance of the elements of the substance of the brain to irradiation by reducing oxidative stress, improve time and total dose of radiation that will have a positive impact on the effectiveness of the treatment I n the patients with malignant brain tumors in different age groups.

The method of treatment of malignant brain tumors in the postoperative period, including a course of radiation and drug therapy, characterized in that the quality of drug therapy prescribed oral administration of memantine 10 mg daily for 5-7 days prior to the start of radiation therapy during radiation therapy prescribed for administration of memantine 20 mg for 4-6 hours before the session, after the end of radiation therapy for patients under the age of 60 years shall receive of memantine 10 mg in 2-3 months daily, patients aged 60 years or more is prescribed reception of memantine 20 mg for 5-6 months daily.



 

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