Method of treating bone sarcomas in children and adolescents

FIELD: oncology.

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.

2 ex

 

The method relates to medicine, namely to Oncology, and can be used in complex treatment of children of primary, secondary and adolescence, and young patients, patients with Ewing sarcoma and osteogenic sarcoma in different stages of the malignant process.

There is a method of treatment of malignant bone tumors in adult patients (see the book "a cancer therapy", reference book, edited by Perevozchikova NI, M, "Medicine", 1993, str-113). The method includes preoperative chemotherapeutic-mechanical treatment, surgery, radiation therapy at different stages depending on the stage of the disease. Introduction chemotherapy is carried out in a continuous 24-hour infusion from the first to the third day. Each schema drug administration is 21 days after the end of the previous course of treatment.

There is a method of treatment of bone sarcomas is intended for the treatment of adults, is particularly inappropriate for the child's body, including the disadvantages that accompany intensive radiation therapy and radiation. Infusion chemotherapy within 24 hours very long, hard tolerated, emergent adverse toxic manifestations of chemotherapeutic agents prolong the course of treatment or make it impossible to continue due to gravity originating the complications.

There is a method of treatment of bone sarcomas in children (see the book "Pediatric Oncology" edited Durnova L.A., Golubenko GV, M "Letter", 1997, str-316), chosen as a prototype. Children and adolescents with osteogenic sarcoma and Ewing sarcoma carry out comprehensive treatment.

Chemotherapeutic treatment of osteogenic sarcoma is conducted according to the scheme of AR, including the introduction of adriamycin (doxorubicin) at a dose of 30 mg/m21, 2, 3 day and the introduction of cisplatin at a dose of 150 mg/m2on the 4th day. After 4 courses of chemotherapy is performed surgical treatment with subsequent courses of adjuvant chemotherapy as described above, or replacing them with second-line drugs (depending on the degree of therapeutic pathomorphosis in the removed tumor).

Ewing sarcoma is a primary vysokokachestvennaya tumor nenastnogo origin, which develops in the bones of the skeleton and adjacent soft tissues. The disease undergoes an intensive integrated treatment: anti-tumor drugs, cyclophosphamide, doxorubicin, vincristine, cisplatin, bleomycin, methotrexate, and others, as well as local effects in the form of radiotherapy or surgical treatment.

Described methods of treatment are effective and can achieve 5-year remission on average 65% of the patients in the early stages of the disease, will not give satisfactory results in the treatment of patients with high-risk groups, and have expressed severe complications and adverse reactions, which affects the duration of treatment and its effectiveness.

The aim of the invention is to improve the immediate and remote results of treatment of osteogenic sarcoma and Ewing sarcoma in children and adolescents, improving the efficiency of anticancer chemotherapy, reduction of side effects and complications from the treatment.

This goal is achieved by the fact that younger children (5 to 12 years) take blood from the cubital vein in an amount of not more than 5% of circulating blood volume at a single injection of chemotherapy drugs in adolescents and young adults with 200 ml; teach 4 courses of chemotherapy for autologous blood by standard treatment for these diseases taking into account the stage in the recommended doses; between 2 and 3 courses of chemotherapy perform radiation therapy for metastatic foci in the lungs in SOD=16-18 Gr, after 4 courses of induction autohemotherapy conduct local therapy to the primary tumor site: radiation and / or surgical treatment and radiation therapy for metastatic lesions in other bones, then spend the consolidation of remission with the use of drugs of the second line.

The invention is a Method of treatment of bone sarcomas in children and adolescents" is new, because it is unknown from the level of the medicine I, in particular Oncology in the treatment of Ewing sarcoma and osteogenic sarcoma in children and adolescents.

The novelty of the invention lies in the fact that conduct a comprehensive treatment of children with osteogenic sarcoma and Ewing sarcoma, including mnogochasovuyu anticancer chemotherapy for autologous blood in combination with radiation therapy and surgical treatment.

"A method for the treatment of bone sarcomas in children and adolescents" is industrially applicable, as may be used in health care, in medical institutions, cancer research Institute and cancer hospital, treating children with cancer.

"A method for the treatment of bone sarcomas in children and adolescents" is as follows: after verification of the tumor process for children and adolescents with osteogenic sarcoma and Ewing sarcoma is a complex treatment, one of the leading components which is mnogometrovaya chemotherapy. Introduction chemotherapy is carried out on autologous blood of the patient.

The first step is to draw blood from the cubital vein in a bottle with logician. The volume of the inflowing blood in children under 12 years of age is not more than 5% of circulating blood volume, calculated by age nomogram, in children older than 12 years, the volume of the inflowing blood on one's back is giving an average of 200 ml.

The second stage is in a bottle with blood injected chemotherapy. The dosage of an administered cytostatics meet the application guidelines and are calculated per meter of the patient's body. A bottle of cytostatic diluted autologous blood of the patient, incubated in an incubator for 1 hour at a temperature of 37 degrees. During incubation, the patient infusion therapy glucosinolate solutions to maintain the osmotic pressure.

After incubation, the chemotherapy drug is injected intravenously at the time indicated in the diagram.

Treatment of Ewing sarcoma conduct the following program: 4-e induction course autohemotherapy (AGHT) scheme VACP: vincristine 1.5 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 1200 mg/m2, cisplatin 100 mg/m2. After 2 courses in lung metastases in a total irradiation of light in SOD=16-18 Gr. Radiation therapy of primary tumor applied after the induction of SOD=50-60 Gy in combination with the introduction of vincristine 1.5 mg/m2and cyclophosphamide 600 mg/m 1 time per week. Consolidation of remission is 2 seven-week blocks using vincristine, doxorubicin, cyclophosphamide, bleomycin, methotrexate, dactinomycin.

Treatment of osteogenic sarcoma start with 4 courses of neoadjuvant IGHT using doxorubicin at a dose of 90 mg/m and cisplatin 100 mg/m2if operability is performed radical surgery; consolidation of remission implemented a 12-month treatment using the scheme AR or alternating courses of EP (etoposide 100 mg/m2, cisplatin 100 mg/m2) and the EU (etoposide 100 mg/m2, cyclophosphamide 750 mg/m2), only 6-8 courses.

Examples of specific performance "method of treatment of bone sarcomas in children and adolescent patients.

Example 1.

Patient D., born in 1984, (and a/b No. 4883/R), was admitted to the pediatric Oncology Department of RNII 22.03.2002 with a diagnosis of Ewing sarcoma with lesions of the right iliac bone, the presence of soft-tissue component in the tissues of the gluteal region and the pelvis; metastatic lesions in both lungs, st. IVB, (T2N0M1pulm.); CL gr. 2. Histological analysis No. 133384-95: Ewing sarcoma. The state of admission was regarded as severe: extreme pain, absentation syndrome, periodic hyperthermia to febrile digits, weight loss of 4 kg After the comprehensive examination, 25.03.02 started induction therapy VACP. Just spent 4 courses; total entered on autologous blood vincristine 8 mg, doxorubicin 240 mg of cyclophosphamide 5600 mg, 500 mg cisplatin On one introduction climbed 200 ml of autologous blood. Between 2 and 3 courses completed radiation therapy to the lungs in SOD=16 is R. During the dynamic observation, according to the radiographs of the chest revealed a significant decrease in the size of metastatic foci in the lungs with 5-6 cm to 0.3-0.2 cm after the first year, and after the second course metastases was not determined radiographically. Induction therapy was complicated by radiation 2 degrees after DHT on the light, it was noted the presence of dyspeptic symptoms 1-2 tbsp. after the introduction of cisplatin, which was quickly stopped by the reception of antiemetics. On the control CT image of the pelvis from 12.07.02. - sclerotic changes in the right iliac bone, soft tissue component is not defined. The second stage of treatment was completed local therapy to the primary tumor site in the form of radiation exposure in SOD=60 Gy, the patient underwent treatment satisfactorily. During radiation treatment for autologous blood was injected once a week chemotherapy: vincristine 2 mg, cyclophosphamide 800 mg With 3.09.02 on 30.01.03 conducted two consolidating seven-week course under the scheme Rosen. Doses and these terms was performed according to the program. Treatment of 2-fold was complicated by grade 3 tbsp., was introduced colonystimulating factors; among other side effects, it is necessary to mention briefly mucositis 2 tbsp., which were stopped after symptomatic treatment. After treatment with a comprehensive survey, the result is which revealed a pronounced clinical effect: not detected metastatic foci in the lungs, sclerotic changes in the right iliac bone (according to x-ray computer research), the patient's General condition was satisfactory, no complaints.

Example 2.

Patient P., born in 1993, (and a/b No. 2310/0), was admitted to the pediatric Oncology Department of RNII 11.02.02 diagnosed with osteogenic sarcoma of the right tibia, IIB century, T2N0M0, CL gr. Histological analysis: No. 4501-507: osteogenic sarcoma. 14.02.03 started 1 year induction polychemotherapy according to the scheme of AR with the introduction of products for autologous blood. The volume of the inflowing blood on one introduction was not more than 5% of the BCC, which was calculated on the nomogram (BCC=4,62 l, 5% 230 ml). One introduction took 200 ml of blood. Total for 1st year introduced: cisplatin 100 mg, doxorubicin 90 mg Treatment satisfactorily. As a result of the treatment of pain disappeared, decreased in size of soft-tissue component, improved health. On the second course of chemotherapy, the parents of the girl are not brought, turned to traditional healers. By the beginning of June 2002, the child's condition has deteriorated: there was a very strong pain in the right lower extremity, which almost starred analgesics, soft tissue component of the tumor reached a large size, the skin over them Izyaslavich, of wounds was observed sustained release of exudates in large quantities, the temperature is and kept on subfebrile figures with periodic rises to 38.5-39 degrees, the girl lost 4.5 kg In a serious condition on the 26.06.02 enrolled in the Department of pediatric Oncology, RNII. With 1.07.02 on 4.07.02 held 2nd course OUGHT scheme AR-dose chemotherapy were similar to the first course. Treatment was complicated by radiation 3 tbsp., mucositis 3 tbsp., oral thrush, CSF was administered. After recovery in the General analysis of blood 23.07.02 performed amputation of the right lower extremity at the level of the middle third of the right femur. In the period from 5.08.02 on 21.03.03 held 8 courses of induction IGHT using alternating courses AP schemes, VCP, EC. Total introduced: doxorubicin 370 mg, etoposide 1000 mg of cyclophosphamide 4600 mg vincristine 1,5 mg Treatment endured satisfactorily, it was mentioned only briefly, dyspeptic syndrome, which was quickly stopped by the introduction of antiemetics. After the treatment, a comprehensive examination, which revealed no signs of generalized disease. With pronounced clinical effect, the patient was transferred in 3 clinical group. In October 2003, is in clinical and laboratory remission.

Technical and economic efficiency "method of treatment of bone sarcomas in children and adolescents" is to increase the effectiveness of treatment. Improve the immediate results of treatment docked pain syndrome, decrease toxicus is their manifestations, improves the General condition and quality of life of sick children. Significantly reduced tumor size, decrease and disappear metastatic lesions that affect long-term results of treatment.

The method of treatment of bone sarcomas in children and adolescents, including chemotherapy and radiation therapy, characterized in that the younger children from 5 to 12 years take blood from the cubital vein in an amount of not more than 5% of circulating blood volume at a single injection of chemotherapy drugs in adolescents and young adults with 200 ml; teach 4 courses of chemotherapy for autologous blood by standard treatment for these diseases taking into account the stage in the recommended doses software; between 2 and 3 courses of chemotherapy perform radiation therapy for metastatic foci in the lungs in SOD=16-18 G, after 4 courses of induction autohemotherapy conduct local therapy to the primary tumor site: radiotherapy and/or surgical treatment and radiation therapy for metastatic lesions in other bones, then consolidate with the use of chemotherapy 2nd line.



 

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