Method for treating patients with glial cerebral tumor

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

 

The invention relates to medicine and can be used in Oncology for the combined treatment mainly astrocytomas brain III and IV grade.

There is a method of treatment of patients with malignant gliomas of the brain, including the consistent application have surgical treatment, radiation and chemotherapy (MS Chamberlain et al. "Practical guidelines for the treatment of malignant gliomas". Western Journal of Medicine, 1998, V.168, No. 2, P.114-120).

The disadvantage of this method of treatment of patients is palliative in nature, i.e. the application of the method allows only prolong the patient's life, but can not hope to long-term remission.

There is a method of treatment of patients with brain tumor, including chemo-and radiotherapy (RF Patent No. 2125871, IPC And 61 To 31/17, publ. 1999), which consists of the combined use hyperfractionated irradiation and chemotherapy bellustina dose of 200-280 mg

The disadvantage of this method is its low efficiency in the treatment of glial tumors that will not reliably increase the life expectancy of these patients, since it is not possible to overcome the high radioresistant potential of tumor cells forming postoperative residual tumor.

The problem posed by the authors, is the increase in life expectancy for the et efficiency chemoradiation treatment by increasing the radiosensitivity of malignant gliomas, suppression of angiogenesis and proliferative activity of the tumor, increasing the cytotoxic activity of some chemotherapeutic drugs, as well as the normalization of the energy balance in patients. Simultaneously, indomethacin protects not affected by the tumor patterns and brain tissue from radiation damage during the course of radiation therapy that improves the comfort of patients ' lives, but also positively affects the timing.

For this purpose, the method of treatment of patients with glial brain tumors, including chemotherapy, radiation therapy before radical dose proposed for 2-3 days before beginning radiation treatment and throughout the course of radiation therapy to schedule an appointment indometacin in a daily dosage of 300 mg, and for 8-14 days before the end of the course or stage of radiotherapy to chemotherapy cycle vincristine in a total dosage of 4 mg and lomustine in total dosage 160-240 mg

In addition, proposed in the conduct of the split course radiation appointed reception indometacin between stages of exposure.

Applied during irradiation indomethacin, an inhibitor of cyclooxygenase (SOH), suppresses the secretion of prostaglandins and thereby increases the radiosensitivity of tumor cells at least 1.3 times; suppresses resistance glial tumor cells to vincristine, and also suppresses Angie the ez and proliferative activity in glial tumors. In addition, the use lomustina will cause damage and tumor cells, protected from the cytotoxic action of vincristine blood-brain barrier.

The method is as follows.

Indomethacin is prescribed for 2 days prior to radiation therapy. The drug is used orally or rectally daily without interruption during the entire course of radiation therapy.

Daily dose indometacin admission per oss is 300 mg (75 mg × 4 times a day), in the case of rectal daily use suppositories 100 mg × 3 times a day. To prevent erosions in the mucosa of the gastrointestinal tract when administered orally prescribe antacids. Radiation therapy can be performed in three modes: standard mode (GENUS-2 Gr 5 times a week to SOD-60 Gy), Hyper rectification (GENUS-1,25 G twice a day with an interval of 4-6 hours to 60-65 Gy) and mode hypofractionation (GENUS-2,5 Gy in 5 fractions per week to 50 Gy). For 8-14 days prior to the completion of radiation therapy is chemotherapy scheme vincristine 2 mg/1 and 8 days, lomustin once per oss on 160-200 mg in 1 day.

Any of the three modes of radiation therapy can be performed by split program. In this case, radiation therapy is conducted in two stages. At 1 stage, radiation therapy is interrupted for SOD 25-32 G, voso Noseda only 2 weeks. During the 2-week break, the patient continues to take indometacin in the above dosage, then radiation therapy is resumed on the 2nd stage and is carried out in the same mode as on 1 stage. Chemotherapy for splitting radiation therapy is performed twice - at the end of the 1 and 2 stages. During the entire course of radiation therapy patients intramuscularly daily in the morning (7-9 a.m.) is entered dexamethasone 4 mg With increase of symptoms of radiation toxicity daily dose of dexamethasone may be increased to 8-12 mg

According to the proposed method of treatment in 11 patients with malignant gliomas of the brain, the monitor showed that the efficiency is quite high. In the long term (2-5 years of observations) in 40% of patients relapse is not revealed. For comparison, the life expectancy in this age group is 8-10 months.

Example 1.

Patient B., 29 years old, he enrolled in the radiology Department 4 weeks after she was done resection of glioblastoma brain. The patient was held split course radiation therapy (interval between 1 and 2 stages up to 14 days) in the Hyper rectification to SOD-65 Gr. The patient began to get indometacin per oss at a daily dosage of 300 mg for 2 days before the start of radiation therapy and continued his PR is eaten during two stages of irradiation and the break between them. Within a split course radiation for 8 days before the end of each stage the patient received 2 cycles of chemotherapy: vincristine - 4 mg 1-8 days, lomustin 200 mg per oss 1 day.

During five years of monitoring the recurrence was not detected.

Example 2.

Patient A., 62, received in the radiology Department a course of radiation therapy according to the scheme standard dose fractionation (2 Gy) up to 60 Gy, after he was removed glioblastoma brain. Welcome indometacin per oss at a dose of 300 mg. started 3 days before irradiation and carried out without interruption during the entire course of radiation therapy. 14 days prior to the completion of radiotherapy he held 1 cycle of chemotherapy vincristine 4 mg 1 and 8 days of the cycle and lomustine 160 mg per oss 1 day cycle. After the dose was 30 Gy in connection with the increase of brain edema dose injected dexamethasone increased to 8 mg, the Patient is monitored for two years, no signs of relapse.

Example 3.

Patient P., 32 years conducted a course of radiation therapy mode hypofractionation up to 50 Grams. Simultaneously with the irradiation of the patient received indomethacin in rectal suppositories in a daily dosage of 300 mg, he carried out 1 cycle of chemotherapy vincristine 4 mg in 1 and 8 days of the cycle and lomustine 240 mg per oss 1 day cycle. 17 months after completion of treatment the patient will satisfy the aspects, signs of recurrence no.

Thus, the use of indomethacin in the above-described scheme allows to achieve a significant increase in the life expectancy of patients with malignant gliomas.

1. The method of treatment of patients with glial brain tumors, including chemotherapy, radiation therapy before radical dose, characterized in that 2-3 days before beginning radiation treatment and throughout the course of radiation therapy prescribed for administration of indomethacin at a daily dosage of 300 mg, and for 8-14 days before the end of the course or stage of radiation treatment cycle of chemotherapy vincristine in a total dosage of 4 mg and lomustine in total dosage 160-240 mg

2. The method according to claim 1, wherein when performing the split course radiation appointed reception indometacin between stages.



 

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EFFECT: improved and enhanced effectiveness of treatment.

3 dwg, 2 ex

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