Method for complex treatment of lymphogranulematosis

FIELD: medicine.

SUBSTANCE: the present innovation includes polychemotherapy and radiation therapy. Moreover, polychemotherapy should be carried out by the following scheme: on the 1st and the 8th d of the first and the third courses it is necessary to introduce doxorubicin, cyclophosphan, vincristine, and since the 1st to the 14th d - procarbazine and prednisolone; moreover, on the 1st and the 8th d of the second and the fourth courses one should introduce doxorubicin, bleomycin, vinblastine, dacarbazine. The method enables to decrease the quantity of late therapeutic complications, improves the results of relapse-free, total tumor-specific survival rate and decreases the number of polychemotherapeutic cycles.

EFFECT: higher efficiency of therapy.

2 ex

 

The present invention relates to medicine, namely to methods of complex treatment of Hodgkin's disease, and can be used in any Oncology (radiology) institution.

Various methods of complex treatment using cyclic chemotherapy and radiation therapy. In the last decade in Russia and abroad the most often used mode of chemotherapy MOPP/ABVD (mustargen, vincristine, procarbazine, prednisone; doxorubicin, bleomycin, vinblastine, dacarbazine), when after 3 courses of chemotherapy according to the scheme of MORR and 3 courses of chemotherapy scheme ABVD radiation therapy radical programme. Use another method of complex treatment with 6 cycles of chemotherapy according to the scheme of CORR (cyclophosphamide, vincristine, procarbazine, prednisone) and a radical program of radiation therapy.

However, this method of complex treatment of chlamydia have several disadvantages. In the case of regimen ABVD and MORR in combination with radiation therapy allows the results of the relapse-free survival does not exceed 80%. In patients with Hodgkin's disease undergoing chemotherapy using the scheme MOPP/ABVD, 3-5% in remote terms after comprehensive treatment of diagnosed nelimpoblastny acute leukemia and in 3-8% of secondary malignancies is haunted tumors.

To reduce the number of late complications, improve the effectiveness of treatment outcomes, reduce the cost of treatment, the patient should receive doxorubicin, cyclophosphamide, vincristine in the first and eighth days, and procarbazine and prednisolone - from the first to the fourteenth day of the first and third course of chemotherapy; and change the mode of administration of doxorubicin, bleomycin, vinblastine, dacarbazine with the first and the fourteenth day of the first and eighth days in the second and fourth course of chemotherapy.

The method is as follows. The patient performed a detailed clinical and instrumental examination, including history taking, physical examination, ECG, functional tests, x-rays and a CT scan of the chest, ultrasound examination of the abdominal cavity and peripheral lymph nodes, laboratory tests. Set the stage of the disease, the major risk factors of adverse prognosis. The diagnosis is confirmed by histological examination. The functional status of the patient is assessed by the Karnofsky scale, it should be noted that low functional status of patients before treatment was not a contraindication to the prescription of cyclic chemotherapy. After this, the patient is assigned to 1 course of chemotherapy on the development of Tannoy us the schema of SNORR: on the first day of the cycle intravenous bolus injected doxorubicin in the estimated dose of 25 mg/m 2, cyclophosphamide in the estimated dose of 600 mg/m2, vincristine in the estimated dose of 1.4 mg/m2. On the eighth day of the cycle is injected doxorubicin, cyclophosphamide, vincristine in the same estimated doses. From the first to the fourteenth day inside accepted procarbazine in the estimated dose of 100 mg/m2and prednisolone in the estimated dose of 40 mg/m2. After completion of the course is a two-week break in treatment (three weeks after the second intravenous chemotherapy). Before the second cycle of chemotherapy, the patient is held control clinical and instrumental examination, including examination, ECG, x-rays of the chest, ultrasound examination of the abdominal cavity, laboratory tests. After this, the patient is assigned 2 polychemotherapy in our proposed scheme ABVD: on the first day of the cycle intravenous bolus injected doxorubicin in the estimated dose of 25 mg/m2the bleomycin in the estimated dose of 10 mg/m2, vinblastine in an estimated dose of 6 mg/m2, dacarbazine in the estimated dose of 375 mg/m2. On the eighth day of the cycle is injected doxorubicin, bleomycin, vinblastine, dacarbazine in the same estimated doses. After completion of the course is a three-week break in treatment. Before the third cycle of chemotherapy, the patient is held control clinical and instrumental examination, including inspection, the KG, radiography of the chest, ultrasound examination of the abdominal cavity, laboratory tests. After this, the patient is assigned 3 polychemotherapy according to the scheme of SNOR. On the first day of the cycle intravenous bolus injected doxorubicin in the estimated dose of 25 mg/m2, cyclophosphamide in the estimated dose of 600 mg/m2, vincristine in the estimated dose of 1.4 mg/m2. On the eighth day of the cycle is injected doxorubicin, cyclophosphamide, vincristine in the same estimated doses. From the first to the fourteenth day inside accepted procarbazine in the estimated dose of 100 mg/m2and prednisolone in the estimated dose of 40 mg/m2. After completion of the course is a two-week break in treatment (three weeks after the second intravenous chemotherapy). Before the fourth cycle of chemotherapy, the patient is held control clinical and instrumental examination, including examination, ECG, x-rays of the chest, ultrasound examination of the abdominal cavity, laboratory tests. After this, the patient is assigned 4 polychemotherapy according to the scheme ABVD. On the first day of the cycle intravenous bolus injected doxorubicin in the estimated dose of 25 mg/m2the bleomycin in the estimated dose of 10 mg/m2, vinblastine in an estimated dose of 6 mg/m2, dacarbazine in the estimated dose of 375 mg/m2. On the eighth day of the cycle is injected doxorubicin, bleomycin, wine is Lastin, the dacarbazine in the same estimated doses.

Restaurovani is carried out 3 weeks after 4 courses of chemotherapy and includes examination, ECG, functional tests, x-rays and a CT scan of the chest, ultrasound examination of the abdominal cavity and peripheral lymph nodes, laboratory tests. Reviewed functional status of the patient on the Karnofsky scale. Upon reaching the full effect or partial effect, at least 70% regression of tumor tissue, the chemotherapy is completed. The patient is assigned a radical program of radiation therapy. At the first stage are exposed to the reservoir above the diaphragm. Cervical-supraclavicular, axillary and mediastinal irradiated with two opposite curly fields with a single focal dose of 2 Gy, the total focal dose depending on the lymph collector brought to 30/36 Gr, followed by local irradiation of residual tumor to the total focal dose of 44 Gy. Three weeks after the end of the first phase of radiation therapy after a brief clinical and instrumental examination is carried out stage 2 of radiotherapy paraaortal region and spleen with two opposite curly fields with a single focal dose of 2 Gy, the total focal dose depending on the lymph collector d is found to 30/36 Gr followed by local irradiation of residual tumor to the total focal dose of 44 Gy. Patients with I, II, IV stage disease on this comprehensive treatment program is complete. Three weeks after completing the second stage of radiation therapy in a patient with stage III Hodgkin's disease after a brief clinical and instrumental examination is stage 3 of radiotherapy iliac and inguinal region with four curly fields with a single focal dose of 2 Gy, the total focal dose depending on the lymph collector brought to 30/36 Gr, followed by local irradiation of residual tumor to the total focal dose of 44 Gy. This comprehensive treatment is complete and the patient is released under dynamic observation. In further conducted follow-up examination of patients with common intervals.

Example 1. Patient B., age 19, outpatient map 637/95. The patient performed a detailed clinical and instrumental examination, including history taking, physical examination, ECG, functional tests, x-rays and a CT scan of the chest, ultrasound examination of the abdominal cavity and peripheral lymph nodes, laboratory tests. Installed stage IIA disease, diagnosed the lesion cervical-supraclavicular limtations their sites on both sides and lymph nodes in the mediastinum. Symptoms of intoxication was not. Of the risk factors of poor prognosis of the disease was observed massive lesions of the mediastinum with mediastinal-thoracic index more than 1/3, four affected area. The diagnosis is confirmed by histological examination - scleronomic variant of chlamydia. The functional status of the patient according to the Karnofsky scale was 90%. When calculating the nomograms in terms of growth, body weight and body surface area corresponded to 1.7 m2. February 10, 1995, the patient is assigned 1 polychemotherapy according to the scheme of SNOR. On the first day of the cycle intravenous bolus entered doxorubicin at a dose of 40 mg cyclophosphamide at a dose of 1000 mg vincristine in the estimated dose of 2 mg On the eighth day of the cycle entered doxorubicin, cyclophosphamide, vincristine in the same doses. From the first to the fourteenth day inside took procarbazine dose of 150 mg and prednisolone in the estimated dose of 60 mg. After completing the course, conducted a two-week break in treatment. Before the second cycle of chemotherapy the patient was held control clinical and instrumental examination, which diagnosed a 50% regression of tumor tissue. After that the patient is assigned 2 polychemotherapy according to the scheme ABVD. On the first day of the cycle intravenous bolus entered doxorubicin at a dose of 40 mg, bleomycin at a dose of 15 mg, vinblastine at a dose of 10 mg, Dakar is asin at a dose of 600 mg On the eighth day of the cycle was administered doxorubicin, bleomycin, vinblastine, dacarbazine in the same doses. After completing the course, conducted a three-week break in treatment. Before the third cycle of chemotherapy the patient was held control clinical and instrumental examination, at which diagnosed positive dynamics in the form of a 70% regression of tumor tissue in the mediastinum, and 100% in the cervical-supraclavicular areas. After that the patient is assigned 3 polychemotherapy according to the scheme of SNOR. On the first day of the cycle intravenous bolus entered doxorubicin at a dose of 40 mg cyclophosphamide at a dose of 1000 mg vincristine in the estimated dose of 2 mg On the eighth day of the cycle entered doxorubicin, cyclophosphamide, vincristine in the same doses. From the first to the fourteenth day inside took procarbazine dose of 150 mg. After completing the course, conducted a two-week break in treatment. Before chetverti cycle of chemotherapy the patient is held control clinical and instrumental examination, in which the degree of regression of mediastinal lymph nodes has reached 80%. After that the patient was prescribed 4 polychemotherapy according to the scheme ABVD. On the first day of the cycle intravenous bolus entered doxorubicin at a dose of 40 mg, bleomycin at a dose of 15 mg, vinblastine at a dose of 10 mg, dacarbazine at a dose of 600 mg On the eighth day of the cycle was administered doxorubicin, bleomycin, vinblastine, Dakara is in the same doses. Restaurovani conducted 3 weeks after 4 courses of chemotherapy, included an examination, ECG, functional tests, x-rays of the chest, ultrasound examination of the abdominal cavity and peripheral lymph nodes, laboratory tests. Diagnosed 90% regression of mediastinal lymph nodes. Revised functional status of the patient according to the Karnofsky scale is 100%. Achieved a partial response with 90% regression of tumor tissue, a program of chemotherapy was completed. The patient began a radical program of radiation therapy. The first stage was exposed to the reservoir above the diaphragm. Cervical-supraclavicular, axillary region and mediastinum were irradiated with two opposite curly fields with a single focal dose of 2 Gy, the total focal dose increased to 36 Gy, subsequently conducted local irradiation of residual tumor in the mediastinum to the total focal dose of 44 Gy and supraclavicular areas to 44 Gy. Three weeks after the end of the first phase of radiation therapy after a brief clinical and instrumental examination, which diagnosed a complete remission conducted stage 2 of radiotherapy paraaortal region and spleen with two opposite curly fields with a single focal dose of 2 Gy, the total focal dose of 36 Gy. The treatment is completed 6 October 1995 and the patient was released under the dynamic is the resource monitor. In further conducted regular follow-up examination. Last - in January 2002. Diagnosed 6 years of complete remission.

Example 2. Patient A., 25, outpatient map 1630/98. The patient performed a detailed clinical and instrumental examination, including history taking, physical examination, ECG, functional tests, x-rays and a CT scan of the chest, ultrasound examination of the abdominal cavity and peripheral lymph nodes, laboratory tests. Installed stage IVA disease, diagnosed the lesion cervical-supraclavicular and axillary lymph nodes on both sides and lymph nodes in the mediastinum, the roots of the lung, right lung, the pericardium. Symptoms of intoxication was not. Of the risk factors of poor prognosis of the disease was observed massive lesions of the mediastinum with mediastinal-thoracic index more than 1/3 of the root lesion of lymph nodes, lung, pericardium, eight of the affected areas, six of which were massively affected. The diagnosis is confirmed by histological examination - scleronomic variant of chlamydia. The functional status of the patient on the Karnofsky scale was 80%. When calculating the nomograms in terms of growth, body weight and body surface area corresponded to 1.96 m2. February 10, 1995 the patient appointed the 1 course of chemotherapy schema SNARR. On the first day of the cycle intravenous bolus entered doxorubicin at a dose of 50 mg cyclophosphamide at a dose of 1200 mg vincristine in the estimated dose of 2 mg On the eighth day of the cycle entered doxorubicin, cyclophosphamide, vincristine in the same doses. From the first to the fourteenth day inside took procarbazine dose of 150 mg and prednisolone in the estimated dose of 60 mg. After completing the course, conducted a two-week break in treatment. Before the second cycle of chemotherapy the patient was held control clinical and instrumental examination, at which diagnosed 70% regression of tumor tissue. After this, the patient is assigned 2 polychemotherapy according to the scheme ABVD. On the first day of the cycle intravenous bolus entered doxorubicin at a dose of 50 mg, bleomycin at a dose of 20 mg, vinblastine at a dose of 10 mg, dacarbazine at a dose of 700 mg On the eighth day of the cycle was administered doxorubicin, bleomycin, vinblastine, dacarbazine in the same doses. After completing the course, conducted a three-week break in treatment. Before the third cycle of chemotherapy the patient was held control clinical and instrumental examination, which further diagnosed positive dynamics in the form of a 90% regression of tumor tissue. After that the patient is assigned 3 polychemotherapy according to the scheme of SNOR. On the first day of the cycle intravenous bolus entered doxorubicin at a dose of 50 mg cyclophosphamide at a dose of 1200 is g, vincristine in the estimated dose of 2 mg On the eighth day of the cycle entered doxorubicin, cyclophosphamide, vincristine in the same doses. From the first to the fourteenth day inside took procarbazine dose of 150 mg. After completing the course, conducted a two-week break in treatment. Before chetverti cycle of chemotherapy, the patient is held control clinical and instrumental examination, in which the degree of regression of the tumor tissue has reached 100%. After this the patient was prescribed 4 polychemotherapy according to the scheme ABVD. On the first day of the cycle intravenous bolus entered doxorubicin at a dose of 50 mg, bleomycin at a dose of 20 mg, vinblastine at a dose of 10 mg, dacarbazine at a dose of 700 mg On the eighth day of the cycle was administered doxorubicin, bleomycin, vinblastine, dacarbazine in the same doses. Restaurovani conducted 3 weeks after 4 courses of chemotherapy, included an examination, ECG, functional tests, x-rays of the chest, ultrasound examination of the abdominal cavity and peripheral lymph nodes, laboratory tests. Confirmed complete remission. Revised functional status of the patient on a scale Karnofsky - 90%. The program of chemotherapy was completed. The patient began a radical program of radiation therapy. The first stage was exposed to the reservoir above the diaphragm. Cervical-supraclavicular, axillary region and mediastinum was irradiated with d the ear opposite curly fields with a single focal dose of 2 Gy, total focal dose increased to 36 Gy, subsequently conducted local irradiation to the total focal dose of 44 Gy. Three weeks after the end of the first phase of radiation therapy after a brief clinical and instrumental examination, which diagnosed a complete remission conducted stage 2 of radiotherapy paraaortal region and spleen with two opposite curly fields with a single focal dose of 2 Gy, the total focal dose of 36 Gy to 6 November 1998. This comprehensive treatment program was completed, and the patient was released under dynamic observation. In further conducted regular follow-up examination. Last - in March 2002. Diagnosed 3 years of complete remission.

From 1990 to 2000, 122 patients treated with morphologically confirmed chlamydia with I - IV stages of the disease. In 20 patients was a complex treatment using chemotherapy CHOPP/ABVD (4 courses), in 102 patients - MORR/ABVD (6 courses).

After a cycle of chemotherapy the objective effect in 100% of patients using CHOPP/ABVD and - 94,1% - way MOPP/ABVD. Radiation therapy has helped significantly increase the number of full effects in the way CHOPP/ABVD from 65% to 100% and when the method MOPP/ABVD - 43.1% up to 86.3%.

Used schemes of chemotherapy had reversible toxicity, enabling the lo in all patients to carry out the administration of cytostatics in strictly required deadlines without increasing the interval between cycles and in compliance with the dosage regimen. Differences in the number of early complications (pneumonitis, esophagitis, etc) was not. Serious complications of the cardiovascular system, we have not recorded. Symptoms of respiratory failure, expressed in 5-10% of patients, associated with the formation of pronounced postradiation of pneumosclerosis. Clinical and laboratory data showing the toxic effect of these drugs on the liver, kidneys we have not received.

Disease-free survival.

Significant differences in the rate of relapse-free survival obtained in 1-5 years after the end of treatment (p=0,012 - 0,022) with a tendency to validity for 6 year (p=0,086). 22% of the variation in survival rates (5-year-old - 100% and 78.9 per cent) say about the advantage of the method of complex treatment with polychemotherapy according to the scheme CHOPP/ABVD.

Overall survival.

Significant differences in overall survival was not detected. In General, about 10% differences in survival rates (5-year - 95% 86,7%), talk about the advantage of the method of complex treatment with polychemotherapy according to the scheme CHOPP/ABVD.

Total tumor specific survival.

Significant differences on this indicator registered at 3 and 4 years (p=0,021-0,045). Marked deterioration in survival with the method included the red treatment with polychemotherapy MOPP/ABVD for 5 year (p=0,096). Overall, 11% of the differences in the rate of tumor specific survival rates at 5 years (100% and 88.9%), talk about the advantage of the method of complex treatment with polychemotherapy according to the scheme CHOPP/ABVD.

Analysis of late complications. Secondary malignant tumors and nelimpoblastny acute leukemia in the way CHOPP/ABVD were not registered, the method MOPP/ABVD is observed in 1% of patients (1 of 102 patients).

The proposed method of complex treatment of Hodgkin's disease has improved the results of the relapse-free and overall tumor specific survival, reduce the time a comprehensive treatment of Hodgkin's disease by reducing the number of cycles of chemotherapy and reduce the cost of treatment.

The proposed method is available in all Oncology (radiology) offices, does not require special training - this opens up broad prospects for its use in medical practice.

Literature

1. Baisogala GD, Afanas'eva N.V., Santarina SV Treatment of chlamydia with the defeat of mediastinal lymph nodes and the involvement of the lungs.//"Meradia." - 1990. No. .5. - S. 10-13.

2. Raemaekers, M.Burgers, M. Henry-Amar et al. Patients with stage III/IV Hodgkin's disease in partial remission after MOPP/ABV chemotherapy have excellent prognosis after additional involved-field radiotherapy: Interim results from the ongoing EORTC LCG and GPMC phase III trial/Annals of Oncology - 1997. - v.9. - 1+. - p.111-114.

The method of complex treatment of Hodgkin's disease, including chemotherapy and radiation therapy, characterized in that polychemotherapy carried out according to the scheme: in the first and eighth days of the first and third courses administered doxorubicin, cyclophosphamide, vincristine, and from first to fourteenth days, procarbazine, and prednisolone; and the first and eighth days of the second and fourth courses administered doxorubicin, bleomycin, vinblastine, dacarbazine.



 

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