RU2130773C1 - Method for treating the cases of kaposi sarcoma - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: method involves administering prospidine into lymphatic system at a dose of 10000-100000 units of action during one procedure each second day 10-15 injections for treatment course. Lidase is to be optionally injected in the amount of 16-48 units of action, prospidine and proteolysis inhibitor are administered in lymphotropic mode. EFFECT: normalized lymphatic system function. 2 cl

Description

 The invention relates to medicine, namely to dermatology.

 A known method of treating Kaposi’s sarcoma with the introduction of vinblastine (see "Treatment of Kaposi" sarcoma with vinblastine, "- Cancer, 1980, v. 45, pp. 427-431).

 The disadvantage of this method is the presence of severe adverse reactions. The drug inhibits lympho-, erythro- and thrombocytopoiesis. Dizziness, nausea, and discomfort in the gastrointestinal tract are noted. A significant disadvantage of vinblastine should be considered its small breadth of therapeutic effect. The drug does not provide prolonged remission. The cytostatic effect of the drug is combined with immunosuppressive - proliferating lymphoid tissue is inhibited.

 There is also known a method of treating Kaposi’s sarcoma, comprising administering an intravenous pharmaceutical composition comprising a compound from the family of drugs that block morphine receptors, and a second compound that facilitates the penetration of the first compound into human body cells (enkephalin and endorphin groups). (French Patent N 9215281, IPC A 61 K 9/08, publ. 1992).

 The disadvantage of this method is the blocking of morphine receptors of the whole organism, including in the cerebral cortex, endocrine glands, hypothalamus, because the effect of the pharmaceutical composition is not selective, i.e., only on the tumor process. Given the trigger action of enkephalin and endorphin and their effect on the biochemical homeostasis of the body, side effects such as general weakness, uncontrolled jumps in blood pressure, disturbances from the central and peripheral nervous system, and the gastrointestinal tract are possible.

 The closest is a method of treating Kaposi’s sarcoma by sequential administration of prospidin with another drug, namely vincristine and prednisolone according to the developed scheme (see A.K. Kalmakaryan and others. Kaposi’s sarcoma, ed. Nauka, 1986, p. 95) .

 The disadvantage of this method is the presence of side effects, such as inhibition of leuko-, erythro- and thrombocytopoiesis, the appearance of general weakness, headache, nausea, lowering blood pressure. The presence of parasthesia, expressed in numbness of the fingers of the hands and feet, face, tip of the tongue, the appearance of cystitis. Combined polychemotherapy causes significant immunosuppression, as well as the development of "withdrawal syndrome" after the end of the course of treatment.

 The task set by the authors to eliminate these disadvantages due to the possibility of pathogenetically substantiated therapy.

 When treating Kaposi’s sarcoma, it was proposed to introduce prosidin in a dose of 50-150 mg into the lymphatic system in series with a proteolysis inhibitor in a dose of 10,000-100,000 units per procedure every other day 10-15 times per treatment course. In addition, it was proposed to additionally subcutaneously administer 16 - 48 units of lidase, while prospidine and a proteolysis inhibitor should be administered lymphotropically.

 With Kaposi’s disease, a proliferative disorder of lymphatic endothelial cells occurs. This tumor is characterized by an increase in the activity of tissue collagenase capable of extracellular cleavage of collagen, which causes invasion and tumor growth.

 The introduction of prospidine to the patient in combination with a proteolysis inhibitor inhibits the proliferation of tumor cells and inhibits the mitotic activity of cells in human tissues, and the introduction of drugs into the lymphatic system creates and maintains their high concentration in nearby and separate organs for a long time, which is of great importance especially in cases with visceral Kaposi’s sarcoma lesions, which sharply worsen the prognosis of the disease and, at the same time, are poorly amenable to clinical and paraclinical diagnosis. The administration of lidase causes lymphotropy, i.e. directed intake of the drug into the lymphatic system.

 With Kaposi’s disease, destructive changes occur around the skin tumor associated with the breakdown of normal areas of skin collagen. Tumor cells produce significant amounts of plasminogen activators and exhibit local fibrinolytic activity, thus contributing to the invasion of normal tissue. An increased level of proteolytic enzymes weakens the antigenic properties of cancer cells, changes the structure of immunoglobulins, and leads to changes in the protective functions of the latter against cancer cells. Therefore, the introduction of drugs into the lymphatic system is pathogenetically substantiated.

 The method is as follows.

 In cases of enlarged inguinal lymph nodes, direct endolymphatic (intranodular) administration of prospidin and a proteolysis inhibitor is used. The patient is laid on his back in a horizontal position. After treatment with the antiseptic of the inguinal region, the palpable inguinal lymph node is fixed with the index and thumb. The latter is punctured with a needle perpendicular to the skin. A solution of prospidine is administered slowly at a dose of 50-150 mg. Then, a proteolysis inhibitor (mainly Gordox or Contrical) is administered in the same way in the lymph node of the opposite inguinal region at a dose of 10,000 - 100,000 units. Drugs are administered every other day 10 to 15 times per course of treatment.

 Cytostatic prosidin has a pronounced tropism for epithelial tissues, one of the most significant advantages of it should be considered a large breadth of therapeutic effect. The proteolysis inhibitor enhances the therapeutic effect of cytostatic, and their combination allows to inhibit the mitotic activity of cells in human tissues.

 In cases where there is no enlargement of the inguinal lymph nodes, indirect endolymphatic (lymphotropic) administration of prospidin and a proteolysis inhibitor (Gordox or Contrikal) is used. At the border of the lower and middle third of the lower leg, along its dorsal surface, 16–48 units of lidase dissolved in 3.0–4.0 ml of novocaine solution are subcutaneously administered. Without taking out the needle, after 4 - 5 minutes, prospidine is administered. A proteolysis inhibitor is injected subcutaneously on the second lower leg, along its posterior surface at the border of the lower and middle third, and immediately put on the cuff from the apparatus for measuring blood pressure in the distal third of the thigh, while creating a pressure of up to 40.0 mm Hg The cuff is removed after 2 - 2.5 hours from the start of the procedure, the patient is in a supine position. The procedure is repeated every other day in doses and with the duration indicated above.

 When the process is localized in the head region, prospidin is injected lymphotropically into the mastoid region. The patient lies on his side. A roller is placed under the neck, the head is in an unbent position. About 1.0 cm below the angle formed by the lower jaw and the sternocleidomast muscle of the head, 32 U of lidase dissolved in 3.0 - 4.0 ml of novocaine are subcutaneously administered. Without removing the needle, after 4-5 minutes, prospidine is introduced into it, and the proteolysis inhibitor is injected lymphotropically into the lower leg. The duration and dosage of the administered drugs is similar to that described above.

 Thanks to the course of treatment, a long-term remission is achieved, while the treatment does not give complications, it is easily tolerated. Depending on the degree of the disease, a course may be repeated up to 5 times in 3 months.

 Example 1

 Patient B., born in 1938 (history. Bol. N 3808), was admitted with a diagnosis of Kaposi's sarcoma, subacute form, complaints of general malaise, lack of appetite, edema of both feet. The presence of rashes of a bluish color in the region of both feet and nodular-like formations on the back of the left hand.

 Lymphotropic, on lidase, introduction of 50 mg of prospidin into the shin per injection was started - a course of 750 mg and lymphotropic administration of Gordox in 100,000 units per procedure. Both drugs were administered every other day.

 From the 7th day from the start of treatment, a decrease in the color of the rashes and a decrease in edema of the feet were noted. On the 15th day, the nodule on the hands settled and equaled to normal skin. On the 30th day: there were no swelling, spots in the area of both feet were pale gray, their number decreased. Improvement in general condition was noted from the 10th day of treatment. After 3 months, the patient was given another course of the indicated therapy in a planned manner. After four courses of chemotherapy, the patient's condition is satisfactory, data for the distribution of the process were not found.

 Example 2

 Patient S., born in 1921, (history. Bol. N 3666), was admitted with a diagnosis of Kaposi's sarcoma, subacute form, chronic lymphocytic leukemia.

 Swelling of the right lower leg and foot, significant skin infiltration, the presence of nodular-like and infiltrative-plaque elements of cyanotic-lilac color in the region of both legs, the presence of spotty rashes on both auricles, an increase in the entire group of lymph nodes to the size of a walnut were noted.

 Prospidine was treated with 50 mg endolymphatically (intranodularly) every other day, at a course of 750 mg and intronodular administration of contracal at 20,000 units every other day, at a course of 15 injections.

 On the 5th day from the start of treatment, a significant pallor of rashes on the ears and a slight decrease in swelling of the right lower leg were noted. On the 8th day, the volume of the lower leg decreased by 4.0 cm, the infiltration of the lesions on both legs was significantly resolved, and the infiltrative-plaque elements became denser. On the 15th day of treatment, the auricles acquired their usual color, the nodal elements on the extremities significantly decreased in size, their color from purplish-cyanotic became pale brown, discomfort in the affected area disappeared. A marked decrease in the size of the cervical and inguinal lymph nodes to the size of a hazelnut was noted. On the 30th day, the patient noted a significant improvement, small tumor elements completely regressed, constituting hyperpigmented and cicatricial atrophy. The volume of the lower leg decreased from 46 to 37 cm. In the future, the patient received 4 courses of this therapy in a planned manner with a good clinical effect. Persistent remission is maintained.

Claims (2)

 1. A method for the treatment of Kaposi’s sarcoma by sequential administration of prospidin with another drug, characterized in that prospidine is administered at a dose of 50-150 mg in combination with a proteolysis inhibitor at a dose of 10,000-100,000 units per procedure every other day 10-15 times on a course of treatment.  2. The method according to claim 1, characterized in that it is additionally administered subcutaneously with 16 to 48 units of lidase, while the prospidine and the proteolysis inhibitor are administered lymphotropically.