RU2265440C2 - Method for pre-operational treatment of mammary cancer - Google Patents

Abstract

FIELD: medicine, oncology.

SUBSTANCE: the present innovation deals with treating malignant tumors of mammary gland in case no tumor penetration into thoracic fasciae. The method suggested includes autohemochemotherapy. Moreover, on the 1^st d of therapy it is necessary to sample 30 ml blood out of patient's peripheral vein into the 1^st vial to combine its content with 500 mg 5-fluorouracil and 600 mg cyclophosphan; then one should sample 20 ml blood into the 2^nd vial to combine its content with 40 mg doxorubicin; both vials should be incubated at 37-37.5 C for 20-30 min, afterwards its necessary to inject the mixtures out of both vials under the tumor and along its circumference. On the 8^th d of therapy one should repeat impact procedures at the same dosages of anti-tumor preparations and at the same order. The innovation suggested enables to develop the largest concentration of anti-tumor preparations in lesion focus, divide into fragments, decrease tumor's size and its inflammatory component and border it against surrounding tissues for performing radical surgical treatment.

EFFECT: higher efficiency of therapy.

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Description

The invention relates to medicine, more specifically to oncology, and can be used in the treatment of malignant breast tumors without penetrating the tumor into the fascia of the chest.

A known method of treating breast cancer, including preoperative systemic antitumor chemotherapy and / or radiation exposure using standard doses of antitumor drugs and / or total focal doses of ionizing radiation (B.E. Peterson. Oncology. M .: "Medicine", 1980).

However, known methods of treatment along with positive effects have a number of disadvantages. The introduction of chemotherapy, especially the latest generation, has a significant damaging effect on the cells of the tumor itself. Along with this, the toxic side effects of the systemic effects of antitumor chemotherapy drugs are so severe that they force them to stop antitumor treatment until the arising disorders of the blood and gastrointestinal tract are restored. Radiation therapy in the preoperative period leads to a violation of the structure surrounding the tumor tissue. This causes teething, suppuration of the surgical wound.

A known method of treating breast cancer using antitumor chemotherapy drugs, connected with the autologous blood of patients. The authors propose the introduction of higher doses of drugs, trying to get a higher effect (Sat. "High Technologies in Oncology", mat. 5 All-Russian Congress of Oncologists, vol. 3, Kazan, 2000).

However, the treatment proposed by the authors, in addition to the increased effect, leads to a large number of toxic side effects of chemotherapy. According to the authors themselves, in some cases there was a need for special therapy to stop the complications that arose. In addition, tissues not affected by a malignant tumor were exposed to chemotherapy drugs.

The aim of the invention is the ability to create the highest concentration of antitumor drug in the lesion and fragmentation of the tumor.

This goal is achieved by the fact that in a patient with breast cancer from a peripheral vein, 30 ml of blood is taken into a bottle with 7 ml of preservative and combined with 500 mg of 5-fluorouracil and 600 mg of cyclophosphamide, a second bottle with 5 ml of preservative is filled with 20 ml of autologous blood and connected with 40 mg of doxorubicin, then both vials are incubated at a temperature of 37-37.5 ° C for 20-30 minutes, on the first and eighth day of treatment, mixtures are administered under the tumor and around its circumference, 14 days after the last injection, surgical removal is performed tumors.

The analysis of known methods of treating breast cancer and the claimed allow us to state that the latter has significant differences and has novelty. The novelty of the developed method consists in saturating the tissues surrounding the tumor with the maximum number of anticancer chemotherapy drugs and thereby creating the highest concentration of the drug around and in the lesion itself.

In available sources of open information in Russia, the CIS countries and abroad similar to the proposed method is not found.

The proposed method for the preoperative treatment of breast cancer is industrially applicable; it can be reproduced and repeatedly repeated in specialized medical institutions of public health.

The method is as follows.

After conducting clinical trials, verifying the diagnosis, determining the degree of spread of malignant neoplasms, the patient is laid on a couch in a supine position. Following the rules of aseptic and antiseptic from a peripheral vein, 30 ml of autologous blood is taken into a bottle with 7 ml of preservative, combined with 500 mg of 5-fluorouracil and 600 mg of cyclophosphamide. A second vial with 5 ml of preservative is filled with 20 ml of autologous blood and combined with 40 mg of doxorubicin. Next, the mixtures are incubated in a thermostat at 37-37.5 ° C for 20-30 minutes, after which the mixture of the first and second vials is introduced on the first day of treatment by moving the needle under the tumor and around its circumference. On the eighth day of treatment, the effects are repeated in the same order and doses of antitumor drugs. 14 days after the last injection, radical surgical removal of the tumor is performed.

An example of a specific application of the method of preoperative treatment of breast cancer can serve as an extract from the medical history.

Patient S., medical history No. 9675 / r, born in 1941, was admitted to the department. OMT RNII on June 30, 2003 complaining of a tumor in the right mammary gland, which was discovered by chance on May 28, 2003. An oncologist from the place of residence was sent to the clinic of the RNII for consultation on June 27. A tumor puncture biopsy was performed in the patient’s mammological office, cytoanalysis No. 13794-95: “cytogram of moderately differentiated carcinoma” and a preliminary diagnosis was made: cancer of the right breast, cT3NxMO, st. II b, class 2. The patient was hospitalized in the department. OMT for special treatment 06/30/2003

Upon admission, she complained of a tumor in the right mammary gland for a month, painless on palpation.

From the anamnesis of life it was found that Botkin’s disease and tuberculosis did not tolerate. There were no injuries. Childbirth alone, abortion 10. I fed the baby for 7 months, there was no mastitis. Menopause since 54 years. Allergic history without features. Heredity is not burdened. Since 1968, after suffering myocarditis, he suffers from a tachysystolic form of arrhythmia. Also, the patient has biliary dyskinesia, chronic cholecystopancreatitis, chronic gastritis with high acidity. Regarding the above diseases, the patient undergoes periodic conservative treatment.

General status. The patient is in an active position, the consciousness is clear, adequate. Normosthenic physique, satisfactory nutritional status. The skin and visible mucous membranes of normal color, without pathological elements. Skin turgor corresponds to age-related changes. The musculoskeletal system without pathology. The thyroid gland is not enlarged, without nodular formations. Auscultation - vesicular breathing over the entire surface of both lungs, wheezing is not heard. Percussion-clear pulmonary sound. Borders of the heart within the age norm. Heart sounds are muffled, blood pressure = 130/90 mm Hg, pulse 70 beats / min., Arrhythmia, tachysystolic form. The abdomen is of the correct form, on palpation it is soft, painless in all departments. The liver is not enlarged. The spleen is not palpable. The chair is decorated, normal color, without pathological inclusions. Periodic constipation. Pasternatsky’s symptom is negative on both sides. Urination is independent, free, painless. Diuresis is adequate. No peripheral edema.

Local status. The mammary glands are developed correctly. The tissue of the left mammary gland is involutively changed, pathological formations in it are not palpable. The nipple-areolar complex is intact. In the right mammary gland, on the border of the upper quadrants of dense consistency, the tumor with irregular contours, tuberous, up to 6 cm in diameter, the skin of the breast in the projection of the tumor is tightened, a positive symptom of the “site”. The nipple is fixed, rotated up. In the right axillary region of dense-elastic consistency, the lymph node is up to 1 cm in diameter, relatively displaced.

Diagnosis: Cancer of the right breast, cT3NxMO, st. II b, cl. column 2. Concomitant diseases: Myocarditis cardiosclerosis, insufficiency 1. Arrhythmia, tachysystolic form. Dyskinesia of the bile duct. Chronic cholecystopancreatitis. Chronic gastritis with high acidity.

The patient before treatment, in addition to general clinical examination, the following additional studies were performed. Ultrasound of the liver (conclusion: the liver is not enlarged, the contours are even, the parenchyma is diffusely heterogeneous, the focal zones are not located), echocardiographic examination (conclusion: atherosclerosis of the aorta. Globally systolic and diastolic functions of the left ventricle are not disturbed. Pathological flows on the valves are not detected, the pericardial cavity intact, arrhythmia). The patient was consulted by a therapist.

Ultrasound of the mammary glands was performed: in the right mammary gland, parenchyma fibrosis, a hypoechoic tuberous formation up to 5.07 × 5.62 cm in diameter is located on the border of the upper quadrants. With CDK, a weak peri-intranodular blood flow. In the left mammary gland - fibrosis of the parenchyma. In the right axillary region, a single lymph node up to 0.9 cm (avascular); conclusion: tumor mam. dexter. A mammogram was performed on the right: in the right mammary gland, on the border of the upper quadrants, a dense shadow formation of approximately 5.0 × 6.0 × 6.5 cm, with uneven tuberous contours, heterogeneous density. Conclusion: blastoma mam. dexter.

Treatment of the patient was started on July 3, 2003. In the treatment room, in the patient’s position, lying on his back on the couch, observing the rules of asepsis and antiseptics, venipuncture of the patient’s left ulnar vein was performed, autologous blood was taken in an amount of 30 ml in a bottle with 7 ml of glugycyr and 20 ml of autologous blood in a second bottle with 5 ml of gluzyzer. 500 mg of 5-fluorouracil and 600 mg of cyclophosphamide were added to the first vial. In a second vial, 40 mg of doxorubicin was administered. The resulting mixtures were incubated in a thermostat at a temperature of 37.5 ° C for 25 minutes. After that, syringes were filled with the contents of the vials and chemotherapy preparations incubated with autologous blood were introduced under the tumor and around its circumference. A similar procedure was performed on July 10, 2003 (on the eighth day of treatment).

Thus, the total doses of drugs were:

doxorubicin 80 mg, 5-fluorouracil 1000 mg and cyclophosphamide 1200 mg. There were no complications during treatment. White blood cells within normal limits: ranged from 5.6 × 10 \ 9 / l to 4.2 × 10 \ 9 / l. There were no dyspeptic phenomena and cardiotoxic effects of drugs. The patient was discharged after a neoadjuvant course of endotumoral autohemochemotherapy to realize a clinical effect for 10 days. On July 21, 2003, a general clinical examination was repeated: all indicators are within normal limits. A second ultrasound examination of the mammary glands and regional zones was performed: the left mammary gland was unchanged. In the right mammary gland, the tumor decreased to 2.04 × 2.6 cm (more than 50% regression), fibrosis, stromal sclerosis around the tumor, and the structure of the tumor is heterogeneous. Lymph nodes unchanged. On the control mammogram on the right: the node described on the mammogram from 02.07.2003, significantly decreased in size, became less dense, fragmented into three parts. The total tumor size is 1.5 × 2.5 × 3.0 cm. Conclusion: the regression of the tumor of the right breast was more than 50%, fragmentation of the tumor.

Local status. The left mammary gland is unchanged. It is difficult to palpate a tumor in the right mammary gland due to perinodular hematoma. The contours are fuzzy, the tumor has decreased in size by half, up to 3 cm in diameter, the texture is softer.

The nipple is not fixed, the upward rotation is negligible. The skin in the projection of the tumor is darker in color. Right axillary lymph node unchanged.

On July 24, 2003, a radical Patey mastectomy was performed on the right under intravenous combined anesthesia with mechanical ventilation.

In the obtained postoperative preparation: a tumor of 2 × 2.5 cm of softened consistency with foci of necrosis, sclerosis, in the center a denser star-shaped area of dirty gray color up to 0.4 cm in diameter. Around the tumor, fibrous cords, areas of necrosis, hemorrhage. In the axillary region of the lipoma in the capsule is up to 1.5 cm in diameter, one lymph node up to 0.6 cm in diameter with hemorrhage in the center. In the subclavian fiber 1 lymph node up to 0.4 cm of the usual structure, brownish in section. In the subscapular tissue lipomatosis.

Histological analysis of July 29, 2003 No. 701977 - 82: after treatment, small complexes of hyperchromic tumor cells, severe necrosis, sclerosis, hemorrhage. There are no metastases.

The postoperative wound healed by primary intention. Sutures were removed on the 7th day after the operation. The patient was discharged for two weeks with the subsequent appearance on the course of postoperative remote gamma therapy using the usual dose fractionation.

The technical and economic effectiveness of the application of the method of preoperative treatment of breast cancer is the possibility of:

- infiltrate the tumor and surrounding tissues with the largest amount of antitumor chemotherapy;

- to achieve a decrease in the size of the tumor itself and the inflammatory component accompanying it;

- to achieve the delimitation of the tumor from the surrounding tissues and conduct radical surgical treatment.

Claims (1)

A method of preoperative treatment of breast cancer, including autohemochemotherapy, characterized in that on the first day of treatment 30 ml of blood are taken from a peripheral vein into a vial, combined with 500 mg of 5-fluorouracil and 600 mg of cyclophosphamide, 20 ml of blood are taken into the second vial and combined with 40 mg of doxorubicin, both vials are incubated at 37-37.5 ° C for 20-30 minutes, after which a mixture of the first and second vials is injected under the tumor and around its circumference; on the eighth day of treatment, the effects are repeated in the same order and doses of antitumor drugs.