RU2340355C1 - Method of medicinal therapy of disseminated malignant neoplasms - Google Patents

Abstract

FIELD: medicine; oncology.

SUBSTANCE: during a course of chemotherapy administer sodium enoxaparin to the patient daily in a dosage of 40 mg a day subcutaneously and in addition, preparation of system enzymotherapy Vobenzyme in a dose of 3 tablets 3 times a day perorally.

EFFECT: potentiation of anticoagulate effect of low-molecular heparins, preventive maintenance of thrombotic complications for the account of lysis of fresh micro and macrothrombuses, prevention of formation of new thrombuses and reduction of microinnidiation process.

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Description

The invention relates to medicine, namely to oncology, and can be used during chemotherapy of malignant tumors.

The use of anticoagulant therapy in oncology is based on data from studies of the hemostatic system in cancer patients. These data indicate that in the body with the development of malignant neoplasms, there is often a state of hypercoagulation up to the development of DIC syndrome [Levin M.N., Lee A.E.E. Risk assessment and primary VTE. Prevention in the cancer patient. Pathophysiol Haemostas Trombos 2003; 33 (1), 36-42, Donati M. B., Cancer and Thrombosis. Haemosnasis 1994; 24: 128-31].

The following mechanisms lead to hypercoagulation:

1. The formation of cancer procoagulant - calcium-dependent enzyme cystine endopeptidase.

2. Strengthening the process of intravascular fibrin formation by tissue factor coagulation of the tumor cell.

3. Thrombin activation during the interaction of 7, 9, 10, 11 coagulation factors with tissue coagulation factor and cancer procoagulant.

4. Isolation of a tumor-necrotic factor that reduces the anticoagulant and fibrinolytic activity of vascular endothelial cells.

An important fact is the participation of the hemostasis system in the growth and metastasis of tumor cells: tumor cells associated with thrombin form microemboli together with platelets, leukocytes, endothelium and metastasize with blood flow. Therapeutic measures - surgical intervention, chemotherapy, radiation therapy further increase the risk of thrombosis in cancer patients.

A known method for the prophylactic administration of low molecular weight heparins to patients with malignant neoplasms [ENOXAN Stady Group (Bergquist D. et al.) Efficacy and safety of enoxaparin versus unfractionated heparin for prevention of deep vein thrombosis in elective cancer surgery: a double-blind randomized multicentre trial with venografic assessment . Brit. G. of surgery. 1997; 84: 1099-103].

The prototype of this invention is a method using low molecular weight heparins for the prevention of thrombotic complications during chemotherapy of malignant neoplasms [A. A. Sukhoverina, V. F. Zavizion, L. T. Artyushenko. Low molecular weight heparins in the complex treatment of patients with locally advanced forms of lung or breast cancer. Oncology. 2002; No. 3, p. 232-233].

The objective of the invention was the search for a method that can more effectively influence the hemostatic system, not only for the prevention of thrombotic complications, but also to enhance the direct antitumor antimetastatic effect.

The technical result of the invention are:

1. Improving the overall effectiveness of the therapy.

2. Potentiation of the anticoagulant effect of low molecular weight heparins, prevention of thrombotic complications (lysis of fresh micro and macro thrombi, prevention of the formation of new blood clots).

3. Reducing the process of micrometastasis.

The proposed method of treatment is as follows. The patient is prescribed a combination of cytostatics necessary for a course of chemotherapy in accordance with the clinical situation. Prescribe a drug of low molecular weight heparins of antithrombotic action enoxaparin sodium subcutaneously at a dose of 40 mg per day and a systemic enzyme therapy drug Wobenzym orally in a dosage of 3 tablets 3 times a day. Drugs are administered daily during the course of treatment.

Wobenzym (Mucos Pharma GmbH & Co., Germany, Russian Medicines Register, Moscow, “Radar-Patent”, 2004; 208) is a combination of highly active plant (bromelain and papain) and animal enzymes (trypsin, chymotrypsin, amylase and lipase) origin with routine.

Wobenzym:

1. has an antithrombotic effect by reducing the degree of adhesion of blood cells and cytokine damage;

2. reduces the likelihood of micrometastasis by reducing the adhesion of tumor cells to blood cells;

3. reduces the number of complications after chemotherapy due to the correction of biochemical processes and immunomodulating properties.

Wobenzym has no toxic, immunogenic and teratogenic properties.

The proposed method is illustrated by the following clinical example:

Patient K., 62 years old, clinical diagnosis: Central cancer of the left lung, art. 3, gr. 4 (disseminated stage). Metastases in the contralateral axillary lymph nodes. Complication: Chronic pain 2 points on a scale of verbal ratings. The histological structure of the tumor is low-grade cancer. After diagnosis, due to the prevalence of the process, chemotherapy was recommended to the patient. Before treatment, a slight tendency to thrombosis was noted in the coagulogram indices. 2 courses of chemotherapy according to the CAP scheme were carried out in standard dosages without any particular effect, a 2-3-fold increase in the coagulogram indices towards hypercoagulation was noted. In this regard, enoxaparin sodium is prescribed at a dosage of 40 mg per day subcutaneously daily. Conducted 2 courses of chemotherapy according to the scheme of EP. After this, a symptomatic effect was noted in the form of a decrease in pain, radiologically - without dynamics. In terms of coagulograms - an increase in hypercoagulation. Since pain reduction and stabilization of the process indicated the need for continued chemotherapy, and an increase in the dosage of enoxiparin from prophylactic 40 mg to therapeutic 80 mg per day in combination with cytostatic treatment was dangerous complications, Wobenzym was additionally prescribed orally 3 tablets 3 times a day. After 2 courses of chemotherapy according to the EP regimen in combination with enoxaparin and wobenzym in the indicated dosages, a positive radiological dynamics was noted - tumor regression by 30%, metastatic lymph node resorption in the axillary region by 30-40%, pain reduction, and overall well-being. In a coagulogram, there is a tendency to normocoagulation. Bleeding, thromboembolic complications during treatment have not been recorded.

Thus, when using the proposed method, there is a potentiation of the anticoagulant effect of low molecular weight heparins, a decrease in the process of tumor micrometastasis.

The proposed method was treated 12 patients. This group includes the following types of neoplasms: 7 cases of disseminated breast cancer, 4 disseminated lung cancer, and 1 - disseminated colorectal cancer. Patients in the group were selected after a clinical examination confirming the presence of distant metastases and determining coagulogram indices - patients with a state of normo- and hypercoagulation were included. The next step was a therapy consisting of:

1. a combination of cytostatics prescribed in accordance with the nosology and clinical situation,

2. accompanying therapy, consisting of antiemetics, glucocorticoids, antihistamines,

3. sodium enoxyparin subcutaneously at a dose of 40 mg per day daily and Wobenzym 3 tablets 3 times a day daily during a course of chemotherapy.

In the group of patients with breast cancer, 5 patients had metastatic bone damage, 2 women had lung metastases. A history of women underwent surgical treatment, radiation therapy for this disease. This group of patients underwent drug therapy with cytostatics in combination with the claimed combination. Chemotherapy regimens 1 and 2 were used for palliative treatment of breast cancer.

The group of patients with lung cancer consisted of men with an initial established diagnosis of malignant neoplasms and who did not receive a special history of treatment. In this group, 3 patients had metastatic lesions of distant lymph nodes, and 1 patient had metastases in the liver. Palliative chemotherapy was carried out in combination with a combination of sodium enoxyparin and wobenzym. The treatment regimens 1 and 2 were used.

In the group of colorectal cancer, the patient had colon cancer with metastatic lung damage. A history of surgical radical treatment followed by adjuvanted patience. Chemotherapy was prescribed for the progression of the disease. Palliative therapy regimens of the 1st line were used in combination with a combination of sodium enoxiparin and wobenzym.

All 12 patients received from 4 to 6 courses of treatment. Complications of mild and moderate toxicity were recorded according to the WHO scale; no bleeding and thromboembolic complications were observed during treatment. The following results were obtained: in 5 patients — stabilization of the process, in 7 patients — positive dynamics according to the results of the control examination. All patients had a positive symptomatic effect.

Claims (1)

A method of treating disseminated malignant neoplasms, including a course of chemotherapy, the administration of a low molecular weight heparin preparation, characterized in that daily enoxiparin sodium is administered at a dosage of 40 mg per day subcutaneously and 40 mg of systemic enzyme therapy Wobenzym 3 times a day as a low molecular weight heparin. per day orally.