RU2178294C2 - Method to treat mammary gland cancer - Google Patents

Abstract

FIELD: medicine, oncology. SUBSTANCE: method deals with nonoperable patients and suggests to apply as a first treatment stage 4-7 injections paratumorally and into soft tissues at lymph outflow route using the following preparations, ml: 0.5%-richlocaine solution, 10; metotrexate, 5-10 mg; diclophenak solution/injection separately, 3; in a day, then at no intervals antitumor chemopreparations should be injected at standard course doses upon autoblood together with 50 mg richlocaine upon autoblood thrice weekly, separately, subsequently, for 2 wk, then the courses of autohemochemotherapy along with richlocaine injection should be repeated after a 2- week-long interval without any preliminary injection of preparations paratumorally and into soft tissues at lymph outflow route out of the mammary gland. EFFECT: higher efficiency of therapy, increased immunomodulating effect, improved chemotherapy tolerance due to decreased body toxic reactions, improved life quality in nonoperable patients at treating local and disseminated mammary gland cancer (III-IV stages) by cytostatic preparations. 3 ex, 8 tbl, 10 dwg

Description

 The invention relates to medicine, namely to oncology, and can be used for the treatment of locally advanced and disseminated breast cancer with cytostatic agents.

 A known method of treating breast cancer by combining antitumor drugs according to the CMFVP scheme, including cyclophosphamide at 2 mg / kg orally or IM for 1-28 days, vincristine at 0.025 mg / kg, methotrexate at 0.75 mg / kg, 5-fluorouracil 12 mg / kg, the last three drugs - iv on 1,8,15,22 days, prednisone 0.75-0.25 mg / kg orally for 3 weeks, then 10 mg for 1 week. The course is designed for 4 weeks, the interval between courses is 4 weeks (see Antitumor therapy. Edited by Translatorova N. I., M., 1996, p. 70).

 The disadvantages of the known method of treating breast cancer are the need to significantly reduce the standard single and course doses of chemotherapy drugs and forced interruptions in therapy due to the occurrence of hematotoxic, dyspeptic and other side effects, which does not allow to observe the strategic principle of the maximum possible radicalism of chemotherapeutic effects. In addition, prednisolone, included in the scheme, has an immunosuppressive effect, exacerbating immunosuppression during a course of chemotherapy. Side effects of corticosteroids - ulcerogenic effects on the gastrointestinal tract, hyperglycemia, hypertension, obesity, osteoporosis, water-salt metabolism disorders and others - cause a wide range of contraindications for treatment (peptic ulcer, duodenal ulcer, other hypertension, diabetes mellitus) common pathological conditions in patients with breast cancer). Meanwhile, other combinations of chemotherapeutic agents created on the basis of this scheme, which do not include corticosteroids (CMF, CMFV, etc.), including those using anthracycline antibiotics, which are currently widely used to treat breast cancer, also do not allow chemotherapy in recommended doses and to adhere to the modes of administration due to toxic side effects, negatively affect the immune system, which ultimately negatively affects the antitumor effectiveness.

The well-known "Method for the treatment of cancer" (see copyright certificate 940379 from 05/15/1980, A 61 K 35/14, authors: Sidorenko Yu.S., Katsman M.V.), we selected as a prototype, involving intravenous administration vincristine, methotrexate, 5-fluorouracil and characterized in that 1/4 of the generally accepted course dose of the drug is dissolved in 50 ml of saline, mixed with 150 ml of autologous blood, incubated at a temperature of 36.5-37 ^o C for 25-30 min and iv drip is administered to the patient - a method of autohemochemotherapy (AHCT).

 This method increases the tolerance of the generally accepted course dose of drugs, overcoming the toxic barrier inherent in systemic polychemotherapy, but also has its drawbacks. Its own limit of toxicity limits the amount of doses of chemotherapeutic agents and lengthens the intervals between administrations, and general toxic manifestations occurring in a certain percentage of cases force interruption of the current course of AHCT. In addition, this method does not allow for the correction of immune status.

 Breast cancer, especially in advanced stages, like other oncological diseases, is accompanied by the development of immunosuppression and impaired regulation of immunopoiesis. The maximum treatment effect of this disease is possible with the use of chemotherapy, which has an antitumor effect without suppressing the body's defenses. In this regard, there is a need for correction of the immune system in the treatment of breast cancer.

 The aim of the invention is to increase the effectiveness of the treatment of locally advanced and disseminated breast cancer, increase patient responsiveness, correct immune status, improve chemotherapy tolerance by reducing toxic reactions of the body, improve the quality of life of inoperable patients.

 This goal is achieved by the fact that the first stage of treatment is performed with 4-7 injections paratumorally and into the soft tissues along the path of lymphatic drainage from the mammary gland of preparations: 10 ml of a 0.5% solution of richlocaine, 5-10 mg of methotrexate, 3 ml of diclofenac solution per administration, separately every other day, then, without interruption in treatment, antitumor chemotherapy drugs are administered in standard course doses on autologous blood in combination with 50 mg of richlocaine on autologous blood 3 times a week, separately, sequentially, for two weeks, then autohemochemical courses Iotherapy in combination with the introduction of richlocaine is repeated after a two-week break without prior administration of the drugs paratumorally and into the soft tissues along the path of lymphatic drainage from the mammary gland.

 The invention "A method for the treatment of breast cancer" is new, since it is not known from the level of medicine in the field of oncology in the treatment of breast cancer with cytostatic agents.

 The novelty of the invention lies in the fact that in the drug treatment of breast cancer, the drug richlocaine is used locally and systemically as an immunocorrector and chemotherapy modifier; they carry out 4-7 injections of paratumoral and into the soft tissues along the path of lymphatic drainage from the mammary gland of a solution of richlocaine, small doses of methotrexate and a non-steroidal anti-inflammatory drug - NSAIDs (diclofenac), after which the patients undergo 2-3 courses of chemotherapy according to the CAMFV regimen with standard course doses of chemopreparations on autologous blood with concurrent administration of richlocaine on autologous blood separately sequentially for 2 weeks: vincristine and methotrexate to a course dose once a week, 5-fluorouracil and cyclophosphamide to a course dose of 3 r aza per week, doxorubicin 1-3 times a week (regimen and dose are adjusted individually), richlocaine - 3 times a week.

 The proposed "Method for the treatment of breast cancer" involves a combination of auto-immuno-immunological, auto-chemo-therapeutic effects and, in addition, a local-regional therapeutic effect on the tumor and metastatically changed lymph nodes. The use of NSAIDs (diclofenac) in our "Method for the treatment of breast cancer" as a blocker of prostaglandins, which are one of the factors of metastasis, and richlocaine, synthesized as a drug for local anesthesia, which does not have antitumor activity, but in combination with chemotherapy enhances its therapeutic effect and promotes correction of the body's immune status, increases the effectiveness of treatment.

 Rihlokain (benzoic ester of 1-allyl-2,5-dimethylpiperidol-4-hydrochloride) is approved for use by the Ministry of Health of the Russian Federation (Order No. 250 dated August 31, 1995, registration certificate No. 95/250/8).

 The experimental justification for the use of richlocaine in the proposed "Method for the treatment of breast cancer."

 In an experiment on animals with a C-45 tumor subcutaneously transplanted, it was found that richlocaine has a modifying effect during chemotherapy with cyclophosphamide (Yu. N. Bordyushkov et al., Autolymphochemotherapy and other oncology issues, M., 1997, p. 278-282).

 In our preliminary experiments, the stimulating effect of richlocaine on the cytotoxic activity of natural killers, which is the most important factor in antitumor protection, was detected during incubation in vitro with cancer lymphocytes. It was established that this effect is provided by two concentrations of richlocaine and depends on the background indicators. The initially high values of the cytotoxic index after the action of richlocaine remain at the same level, and the initially low values increase statistically significantly (Table 1).

 The invention has an inventive step, as for a specialist oncologist-chemotherapist does not explicitly follow from the level of medicine in the treatment of breast cancer.

 The proposed "Method for the treatment of breast cancer" is original, not obvious, and does not explicitly follow from the level of medicine in this field of oncology - the treatment of locally advanced and disseminated breast cancer - neither in the CIS, nor in Russia, nor abroad.

 The invention is industrially applicable, as it can be used in healthcare for chemotherapy of breast cancer in various medical institutions, especially oncology, in the Oncology Research Institute, oncology dispensaries.

 The specific implementation of the "Method of treating breast cancer."

10 ml of a 0.5% solution of richlocaine, 5-10 mg of methotrexate diluted in 5 ml of saline and 3 ml of diclofenac solution are collected in separate disposable syringes and sequentially injected with a breast cancer patient through a single needle paratumorally and into soft tissues along the path of lymphatic drainage from the breast. Such injections are made every other day with a total number of 4-7, depending on the therapeutic effect. Then, without interruption in treatment, patients undergo the 1st course of AHCT according to the CAMFV scheme with the parallel administration of richlocaine. 200 ml of blood are taken from a patient from the ulnar vein, 100 ml in 2 bottles with a blood preservative "Glyugitsir". 50 mg of richlocaine (10 ml of 0.5% solution, 5 ml of 1% solution, 2.5 ml of 2% solution) is injected into autologous vial N1. Chemotherapy drugs are introduced into vial 2 with autoblood, previously diluted each in a separate syringe in 10 ml of saline. Both vials are incubated in a thermostat at a temperature of 37.5-38 ^o C for 25-30 minutes and sequentially (vial N1, vial N2) is introduced through one system in / drip 3 times a week. The combination of chemotherapy and richlocaine is designed for 2 weeks. The introduction is carried out in the following mode: vincristine - 1 mg, methotrexate - 25 mg in 1.8 days, 5-fluorouracil - 500 mg, cyclophosphamide - 200 mg in 1,3,5,8,10,12 days, doxorubicin 30 mg in 1, (3,5), 8, (10,12) days (the frequency of administration is determined individually depending on the state of the patient's cardiovascular system), richlocaine - 50 mg on 1,3,5,8,10,12 days. The subsequent courses of AHCT are repeated after a two-week break without prior administration of the drugs paratumorally and into the soft tissues along the path of lymphatic drainage from the mammary gland.

 After injections, the general condition of the patients is monitored, laboratory control is carried out: a general blood test 2 times a week, a biochemical blood test, a general urine test 1 time per week, an electrocardiogram, an immunogram, an ultrasound examination of the mammary gland and lymph nodes before and after treatment.

 Clinical and immunological results of the use of the "Method for the treatment of breast cancer."

 Twenty primary patients with locally advanced and disseminated breast cancer (stage IIIB-IV) underwent treatment with the proposed “Method of treating breast cancer”. The group included patients aged 34 to 70 years (average age - 53.9 years). In 8 of them, menstrual function was preserved, 12 were in menopause. According to the degree of tumor prevalence, patients were characterized as follows. A locally advanced process without going beyond the breast and without distant metastases (signs of a locally advanced process and primary inoperability of breast cancer were established taking into account the Colombian clinical classification - Haagensen CD, 1978, Donegal WJ, 1979) were found in 7 patients (with T3-4 N1 MO - two, with T4 N2 MO - five). The generalized form (T4 N1-2 M1) was detected in 13 patients: the spread of the tumor outside the breast with the transition to the soft tissues of the chest wall - in three, the defeat of the supraclavicular lymph nodes on the same side - in two, bilateral involvement in the metastatic process of the cervical supraclavicular and axillary lymph nodes - in three cases, and a combination of distant metastases to the lymph nodes, skin, soft tissues and visceral organs - in five patients (bones - 2, lungs -1, bones and lungs - 1, liver - 1). Nodular form was found in one patient, in the rest - nodular with secondary edema or edematous-infiltrative.

 To assess the effectiveness of the "Method for the treatment of breast cancer", a control group of 19 patients was formed. By age, state of ovarian-menstrual function, the degree of prevalence of the group process were comparable. Patients in the control group were exposed to AHCT with the same drugs, in the same doses and mode as the patients of the main group, but without richlocaine.

 The direct clinical effect was compared separately after one and two chemotherapy courses. Laboratory control was carried out: a general blood test 2 times a week, a biochemical blood test, a general urine test 1 time per week, an electrocardiogram, an immunogram before and after treatment. To objectify the change in the size of the tumor and lymph nodes in the treatment process, the sonographic method was used predominantly.

 After 4-7 injections of the drugs paratumorally and into the soft tissues along the lymphatic drainage pathway (before the start of AHCT), we observed a positive dynamics in the patients' condition: improvement of well-being, disappearance of pains in the mammary gland, which occurred in 11 women, a significant decrease in breast edema glands in all patients with nodular with secondary edema and edematous-infiltrative forms of the disease, a reduction in infiltration of soft tissues of the chest wall outside the gland, observed in 6 cases, a decrease in the height and brightness of exophytes in 9- ty patients.

 A comparative analysis of the effectiveness of the proposed "Method for the treatment of breast cancer" and AHCT without richlocaine is presented in table. 2 and 3.

 After the first course of AHCT, an objective response to treatment, assessed as tumor regression by 50% or more, was 2 times more frequent (65%) in the group of patients receiving richlocaine than in the control group (31.6%). In contrast to control, there was not a single case of process progression.

 Sixteen patients in both groups underwent two courses of AHCT. After 2 courses, an objective response to treatment in the main group was also observed significantly more often (87.5%) than in the control group (65%). There were no cases of disease progression during treatment in the main group; in the control group, 3 patients had new metastases in soft tissues and lymph nodes.

 Of the 20 initially inoperable patients in relation to whom the “Method for the treatment of breast cancer” was applied, 13 patients were successfully operated on, the rest due to the prevalence of the process, surgical treatment was not advisable.

 For a comparative assessment of the toxicity of the two methods, side effects of 38 courses of standard AHCT and 40 courses of modified AHCT with richlocaine were analyzed (see Table 4). Assessment of the severity of side effects was carried out in accordance with the recommendations of the WHO and the international anti-cancer union for toxicity, providing for 5 degrees from 0 to 4.

 Although there were no significant differences in the incidence of leukopenia with the compared treatment methods, from the table. 4 shows that there is a tendency to maintain the normal number of leukocytes and less pronounced leukopenia with modified AHCT, in contrast to the standard. A decrease in the number of leukocytes in peripheral blood when richlocaine was included in the treatment regimen occurred later, was more short-term, did not require special treatment, and statistically significantly less often led to interruption of chemotherapy (5% compared with 21%). Most patients initially had moderate anemia (I-II degree), no significant changes in red blood counts during treatment were noted. There were no cases of thrombocytopenia.

 Regarding the toxic side effects of chemotherapy from the gastrointestinal tract, stomatitis was significantly less common with modified AHCT than with standard, less pronounced, was mostly delayed and did not require special treatment. At the same time, 5 out of 38 courses of standard AHCT were interrupted due to the development of stomatitis. Diarrhea was also less common with AHCT with richlocaine. Nausea and vomiting, which occurred at the same frequency with both methods of treatment, were transient in nature, quickly stopped with antiemetics, and did not require interruption of AHCT.

 Alopecia with both variants of AHCT developed in 100% of cases.

 Other side effects of chemotherapy, such as cardiotoxicity, skin reactions, occurred infrequently (up to 5%), there were no significant differences between the methods.

 A study of the patient’s immune status in dynamics showed that the inclusion of richlocaine in the complex therapy of breast cancer leads to an improvement compared with AHCT without richlocaine.

 At the end of 2 courses of modified AHCT, a statistically significant increase in the number of T-lymphocytes, normalization of the immunoregulatory index (CD4 + / CD8 +), an increase in the functional activity of T and NK cells, expressed in an increase in the mitogenic response to PHA and ConA, as well as an increase in cytotoxic index in the cytotoxic test with target cells K 562 in comparison with AHCT without richlocaine (see table. 5).

 Thus, the drug richlocaine has immunomodulatory properties found both in in vitro experiments and when it is included in the complex treatment of patients with breast cancer, which, in our opinion, accounts for the better clinical effect compared with standard AHCT. In our opinion, this is associated with a lower frequency and severity of adverse reactions in patients receiving richlocaine compared with the control group. Correction of the immune status with richlocaine is an essential component of the proposed "Method for the treatment of breast cancer."

Examples of specific applications of the "Method for the treatment of breast cancer"
Observation 1.

 Patient M., 50 years old (IB N 12074 / f), menstrual function preserved. She entered the Department of Chemohormone Therapy of the RNII in January 1999. She complained of weakness, pain in the mammary gland, the presence of a tumor and an ulcer in the mammary gland. About 1 year ago, I noticed a tumor in the mammary gland in the form of an exophyte at the border of the upper quadrants, at the site of which an ulcer formed after 9 months.

 At the initial examination (see Fig. 1): the right mammary gland is pulled up, smaller than the healthy left, has the shape of a hemisphere with a diameter of 15 cm, very dense, completely occupied by the tumor, completely motionless relative to the chest wall. Infiltration of soft tissues outside the gland extends upward to the clavicle, laterally - to the posterior axillary line. In the upper outer quadrant of the gland, with a transition to the upper inner quadrant at the border with the chest wall, there is a crater-like purulent ulcer measuring 7.5x5 cm, 4 cm deep with dense rigid walls and a bottom that bleed easily upon contact, along the edges is a crimson-colored infiltrative shaft up to 1 cm high .In place of the areola - superficial ulcer 5x5 cm. The nipple is retracted, fixed. The skin over the gland in the preserved areas is infiltrated, tense, completely non-displaceable, a positive symptom of "lemon peel" and multiple skin metastases up to 0.5 cm in diameter are determined. There is no skin sensitivity over the gland; a puncture biopsy is extremely painful. In the axillary region on the right, a single sedentary lymph node with a diameter of 1.5 cm is palpated. In the supraclavicular regions on the right and left, in the axillary region on the left there are dense lymph nodes up to 1 cm in diameter.

 C / a N 12149: "atypical carcinoma cells." From other organs and systems, pathological changes were not detected.

 Diagnosis: Cancer of the right breast, ulcerative form with spread to the soft tissues of the chest wall, metastases to the skin of the gland (satellite), axillary and supraclavicular lymph nodes from 2 sides, T4N2M1, stage IV.

 The treatment started with the introduction of paratumoral (under the gland) and into the soft tissues along the path of lymphatic outflow from the mammary gland of richlocaine, methotrexate and diclofenac according to the above method. After 3 injections, the patient's subjective condition improved, pains in the breast area disappeared, soft tissue infiltration outside the gland decreased: from the top to the III rib, laterally to the middle axillary line, the mobility of the gland relative to the chest wall appeared, the infiltrative shaft at the edges decreased ulcers.

 Then the patient underwent 3 courses of AHCT according to the CAMFV scheme with richlocaine according to the proposed technique with a two-week break. Each course was designed for 2 weeks. The total doses of the drugs for 3 courses were: vincristine - 6 mg, methotrexate - 190 mg, 5-fluorouracil - 8000 mg, cyclophosphamide - 3600 mg, doxorubicin - 300 mg, richlocaine - 750 mg.

 After 3 courses of AHCT (see Fig. 2), soft tissue infiltration outside the gland completely disappeared, soft tissue and skin were released along the periphery of the gland, so that it became mobile relative to the chest wall. A 7x8 cm tumor was palpated in the central part of the gland. The purulent ulcer at the border of the upper quadrants was completely cleansed, significantly reduced, and after 3 courses it presented a surface ulcer of 4x2 cm with soft edges and a bottom, a clean pink epithelizing surface. Metastases to the skin of the gland and lymph nodes completely regressed. A superficial ulcer remained at the site of the areola. Restored skin sensitivity over the surface of the gland.

 Of the complications, the patient had delayed stomatitis of the II degree after the 2nd course, leukopenia of the II degree (up to 2.8) after the 2nd course and 1 degree - after the 3rd, nausea, alopecia.

 The study of the patient’s immune status in dynamics revealed an improvement in the treatment process (see table. 6), which consists in increasing the absolute number of T-lymphocytes, immunoregulatory and cytotoxic indices.

 After 3 courses of AHCT with richlocaine, the patient managed to perform a simple mastectomy on the right, r \ a 534464-71: "infiltrating ductal carcinoma with invasion of the dermis, stromal sclerosis", healing by first intention. Subsequently, the patient underwent distance gamotherapy in the path of lymphatic drainage and metastasis zone and multi-course polychemotherapy.

 Observation 2.

 Patient D., 43 years old (IB N 23 \ k), menstrual function preserved. She entered the Department of Chemohormone Therapy of the RNII in February 1999. She noticed a tumor in the right mammary gland 3 years ago, the last 6 months - rapid growth.

 On examination (see Fig. 3): the right mammary gland is swollen, enlarged, significantly larger than the left, mobility relative to the chest wall is limited. The skin over the gland is pale, swollen, in the form of a "lemon peel." Areola infiltrated, pale. Nipple retracted, not displayed. In the gland, 3 tumor nodes are palpated. The largest (tumor N1) - 7x8 cm (with ultrasound -5.6x4.3 cm - see Fig. 5a) - occupies the lower quadrants and the central part of the gland, the skin grows (exophytic bluish-red color 5x5 cm, height up to 1 cm, in the central part a small ulcer - 2x0.7 cm, covered with a dry crust). The second largest node (tumor 2) is in the caudal region of the gland with a size of 3.5x4 cm (with ultrasound - 3.2x4.3 cm - see Fig. 5b). The third (tumor 3) - on the border of the outer quadrants, size 3x2 cm (with ultrasound - 1.9x1.8 cm - see Fig. 56), fixes and retracts the skin. In the axillary region, there is a sedentary, dense, tuberous conglomerate of lymph nodes 8x5 cm in size (with ultrasound, the lymph node 3.9x2.5 cm - see Fig. 5c), in the upper part it is soldered to the skin. The soft tissues of the axillary region are swollen. Other lymph nodes are not palpable.

 Ts \ a N46-49: "carcinoma". From other organs and systems, pathological changes were not detected.

 Diagnosis: Cancer of the right breast, nodular form with multicentric growth, germination and ulceration of the skin, secondary edema, metastases in the axillary lymph nodes, T4M2MO, stage IIIB, class. group II.

 Treatment began with paratumoral administration into the soft tissues along the path of lymphatic outflow from the mammary gland of richlocaine, methotrexate and diclofenac. After 7 injections, the edema of the gland significantly decreased (the mammary glands are about the same size), the symptom of the "lemon peel" is less pronounced, the size of the tumor nodes in the mammary gland by palpation and according to the ultrasound data decreased: tumor N1 - 4.5x4 cm (ultrasound - 3.5x4). 6 cm), exophyte - 4х3 cm, tumor N2 - 3.5х3 cm (ultrasound - 2.2х1.6 cm), tumor N3 - 1.5х1.5 cm (ultrasound - 1.2х0.7 cm).

 Then the patient underwent 2 courses of AHCT according to the CAMFV scheme with richlocaine according to the proposed method with a two-week break. Each course was designed for 2 weeks. The total doses of the drugs for 2 courses were: vincristine - 4 mg, methotrexate - 135 mg, 5-fluorouracil - 4500 mg, cyclophosphamide - 1500 mg, doxorubicin - 130 mg, richlocaine - 850 mg.

 After 2 courses of treatment (see Fig. 4), the edema of the gland completely disappeared, the symptom of "lemon peel" is not detected, the nipple is retracted, the areola is intact, at the border of the lower quadrants the tumor is 4x2.5 cm (ultrasound - 3.7x2.0 cm - see Fig. 6), in the place of the exophyte there is a "site" of 3x3 cm, other tumors in the mammary gland are not palpated and are not located. In the axillary region - a chain of dense lymph nodes with a diameter of up to 1 cm and a length of 4 cm, mobile, with ultrasound are not located.

 Of the complications, severe nausea and incoming vomiting, stopped by antiemetics, short-term leukopenia (up to 3.3) at the end of the 2nd course were noted.

 Immunological studies in dynamics revealed an improvement in the indicators of the immune status during treatment (see table. 7), which consists in increasing the absolute number of T-lymphocytes, their functional activity, immunoregulatory and cytotoxic indices.

 The patient underwent a radical mastectomy according to Patty on the right, g \ a N 534575-82: "infiltrating ductal cancer, focal fibrosis, focal fibrosis in the subcutaneous tissue, cancer metastasis in the subclavian tissue".

 Observation 3.

Patient D., 42 years old (IB N 10860 \ k), menstrual function preserved. She entered the Department of Chemohormone Therapy of the RNII in October 1999. Complaints about a tumor in the right mammary gland, an increase in axillary lymph nodes, severe pain in the tumor area, weakness, temperature rises in the evening to 37.5 ^o C. I noticed a tumor in the right mammary gland 2 years ago, last 2 months - rapid growth.

 On examination (see Fig. 7a, b): a patient with asthenic physique, sharply lowered nutrition. The mammary glands are small, flabby, about the same size. The skin over the gland is pale, turgor is reduced. In the lower quadrants there is swelling of the skin of the type of lemon peel. Areola infiltrated. The nipple is rotated and pulled up. High on the border of the upper quadrants and the chest wall, a 5.5 × 5 × 4 cm tumor (ultrasound - 5.1 × 3.4 cm - see Fig. 9) with a bright red shiny exophyte 4 × 3.5 cm with ulceration in the center, is motionless, dense, very painful on palpation. Due to the slight severity of subcutaneous fatty tissue at the site of tumor localization, the latter actually "lies" on the chest wall. In the axillary region, there is a sedentary, dense, tuberous conglomerate of lymph nodes 4x3 cm in size (with ultrasound, lymph nodes are 3.5 and 1.1 cm in diameter). Other lymph nodes are not palpable.

 Ts \ a N18967-68: "moderately differentiated carcinoma." From other organs and systems, pathological changes were not detected.

 Diagnosis: Cancer of the right breast, nodular form with exophytic growth, ulceration of the skin, secondary edema, metastases to the axillary lymph nodes, T4N2MO, stage IIIB, cells. group II.

 Treatment began with the introduction of paratumoral richlocaine, methotrexate and diclofenac. After 5 injections, the general condition of the patient improved, the temperature returned to normal, the pain disappeared. Locally, some tumor mobility relative to the chest wall appeared, the height of the tumor decreased to 3.5 cm, the exophyte turned pale, the axillary lymph node became more mobile.

 Then the patient underwent 2 courses of AHCT according to the CAMFV scheme with richlocaine according to the proposed method with a two-week break. Each course was designed for 2 weeks. The total doses of the drugs for 2 courses were: vincristine - 4 mg, methotrexate - 125 mg, 5-fluorouracil - 2000 mg, cyclophosphamide - 2400 mg, doxorubicin - 300 mg, richlocaine - 650 mg.

 After 2 courses of treatment (see Fig. 8a, b), the edema of the gland completely disappeared, the symptom of "lemon peel" is not detected, the areola is intact, the tumor is 3.5x2.5 cm (ultrasound - 3.2x2.0 cm - see Fig. 10), movable relative to the chest wall. In the axillary region - a lymph node with a diameter of 1 cm, with ultrasound is not located. Of the complications - stomatitis of 1 degree at the end of the 2nd course.

 The study of the patient’s immune status in dynamics revealed an improvement in the treatment process (see table. 8), which consists in increasing the absolute number of T-lymphocytes, their functional activity, and immuno-regulatory index.

 The patient underwent a radical mastectomy according to Patty on the right, g / a N 572134-38: "infiltrating ductal cancer, fibrosis and stromal hyalinosis", healing by first intention. Subjected to postoperative remote gamotherapy.

 The technical and economic effectiveness of the “Method for the treatment of breast cancer” lies in the fact that the consistent local and systemic non-traditional use of the drug richlocaine in combination with exposure to anticancer drugs in standard course doses administered to autologous blood increases the effectiveness of the treatment of breast cancer, increases the operability of patients, it has an immunomodulatory effect, improves chemotherapy tolerance by reducing the toxic reactions of the body, improves the quality of life of patients inoperable cases.

Claims (1)

 A method of treating breast cancer, including autohemochemotherapy with intravenous drip administration of antitumor chemotherapy drugs, characterized in that the first stage of treatment is 4-7 injections of paratumoral and soft tissue along the path of lymphatic outflow from the mammary gland of preparations: 10 ml of 0.5% richlocaine solution, 5 -10 mg of methotrexate, 3 ml of diclofenac solution per administration, separately, every other day, then without interruption in the treatment, antitumor chemotherapy drugs are administered in standard course doses to autologous blood in combination SRI with 50 mg Rihlokain on autologous 3 times a week separately, sequentially for two weeks, followed by courses autohemochemotherapy in conjunction with administration Rihlokain repeated after a two-week break, without prior administration of drugs paratumoralno and soft tissue in the path of the lymph breast.

Images