CHEMOTHERAPY OF TUMOURS

From Big Medical Encyclopedia

CHEMOTHERAPY of TUMOURS

(chemistry + Greek therapeia treatment) — use with the medical purpose at malignant new growths of the pharmaceuticals having ability to slow down proliferation of tumor cells or is irreversible them to damage.

The term «chemotherapy of tumours» took roots in experimental and clinical oncology not only in the USSR, but also in many countries of the world. In a broad sense this term reflects all types of medicinal treatment of malignant new growths (see Tumours) and leukoses (see), connected with influence pharmakol. funds directly for a tumor. Sometimes at treatment of new growths hormones or their synthetic analogs apply the term «hormonal therapy». However fullestly all aspects of X. the lake reflects the concept «medicinal therapy of tumours» including use of synthetic drugs, substances of a natural origin, antibiotics, hormones and other antineoplastic means (see).

Historically X. the lake inherited many principles of chemotherapy inf. diseases (see Chemotherapy). However between infectious and tumoral processes there are basic distinctions. Characterizing them, I. V. Davydovsky (1969) wrote that attempts to prove chemotherapy of tumors by analogies to the corresponding methods of treatment inf. diseases are theoretically not quite lawful since tumor cells are only cells of an organism, and microorganisms are complete organisms. Speaking

about distinctiveness of chemotherapy of tumors, L. F. Larionov (1962) emphasized: «If at infectious diseases of the phenomenon of immunity and other defense reactions play a large role in the course of recovery, then at malignant tumors protective forces of an organism are rather weak and often is not able to destroy even a small amount of the cancer cells which remained and kept viability».

Works on creation of new antineoplastic means are directed to receiving such drugs, to-rye at the maximum inhibiting impact on tumor cells would have the minimum damaging effect on normal cells and body tissues. To a crust, time, despite achievements of molecular biology, geneticists, biochemistry and virology of tumors, are absent data on such features of biology of a tumor cell, to-rye would give the chance to accurately formulate theoretical premises to creation of antineoplastic means. Search of antineoplastic drugs is carried out empirically, preferential among tsitostatik. In this regard the existing means are not among acting selectively

and, having antineoplastic effect, exert collateral impact on normal, first of all intensively proliferating fabrics — marrow, an epithelium of a mucous membrane of intestines, follicles of hair, gonads.

The antineoplastic effect can be reached in the different ways: by the direct damaging effect of drug on a tumor cell; increases in time of generation of tumor cells so that they practically cease to breed; the damage of cells leading to the termination of innidiation and invasiveness; stimulations immunol. the reactions directed to tumor cells; corrections of exchange disturbances of tumor cells then they become dependent on regulatory mechanisms of an organism. In a crust, time practical value has use of the direct damaging effect of antineoplastic drug, and the others are at a stage of theoretical developments. In this regard antineoplastic means are applied, as a rule, in the most tolerable doses for the purpose of defeat of all tumor cells, i.e. the principle of chemotherapeutic radicalism for the achievement which is most expressed to lay down is carried out. actions.

More than 50 antineoplastic means entered a wedge, practice and certain success at medicinal therapy of a number of tumors is in recent years achieved. To a crust, time there is no universal remedy rendering to lay down. effect at the majority or many existing malignant tumors. As a rule, the action spectrum of this or that a cytostatics (or hormonal drug) is limited to new growths of several localizations, and sometimes only one tumor or it morfol. option.

On the basis a wedge, and pilot studies philosophy of X are formulated. lakes are also revealed the nek-ry conditions defining to lay down. effect of antineoplastic drugs. The following belongs to the philosophy of chemotherapy of tumors having practical value: selection of drug according to a range of its antineoplastic action; the choice of an optimum dose, mode and route of administration of drug, providing a possibility of receiving to lay down. effect without irreversible by-effects; the accounting of the risk factors demanding correction of doses and modes in order to avoid heavy complications of chemotherapy. Antineoplastic means should be applied when the diagnosis of a tumor is confirmed by means of methods gistol. researches; to lay down. the effect of chemotherapy should be estimated on objective indicators, to-rye reflect reaction of a tumor to antineoplastic drug; it is not necessary to apply chemotherapy if there are no conditions for the corresponding inspection and treatment of the possible side effects caused by antineoplastic drugs.

On a way (ways) of use of antineoplastic drugs distinguish system, regional and local X. lake. To system X. the island belongs administration of drugs inside, subcutaneously, intramusculary, intravenously or rektalno; it is expected the cumulative (resorptive) antineoplastic effect. Regional X. the lake means a possibility of influence by the increased concentration a cytostatics on a tumor and restriction of receipt it in other bodies by infusions in krovosnabzhayushchy new growths of an artery or partial perfusion (see). At local X. lakes of a cytostatics in the corresponding dosage forms (ointments, solutions) apply on the superficial tumoral centers (skin ulcers), enter into serous cavities (at exudates) or into the spinal canal (at defeat of a meninx).

Allocate monochemotherapy when cytostatics use as the only medicine and combined by X. the island (polychemotherapy) when it is used in a combination with other cytostatics and hormones. Mono-himioteragshya gives way to the combined chemotherapy, at a cut as a result of use of two-three and more tsitostatik at the same time or in various sequence, sometimes together with glucocorticoids more and more (see. Glucocorticoid hormones), efficiency of X is possible to raise. lake. Rules of drawing up similar combinations, to-rye are established empirically, are: use of drugs, each of to-rykh it is active concerning a tumor of this localization and is various on the mechanism of action; use of the tsitostatik differing on toxic action.

When the chemotherapy is applied as a component of the combined or complex treatment of malignant tumors, it call additional, or adjuvant. Usually this term belongs to mono - or the poly-chemotherapy appointed after radical and palliative operations, but can be used also when X. the lake precedes radiation therapy of a new growth.

Experimental and the wedge, researches showed that efficiency of use of antineoplastic drugs is defined, in addition to a dose, the mode of use (number of introductions, intervals between them and repeated courses), the nature of tumoral process and the previous treatment, some other signs and conditions. So, quickly growing tumors are more sensitive to chemotherapy; as a rule, there are distinctions in sensitivity of metastasises and primary >op-care. Efficiency of chemotherapy is usually inversely proportional to the mass of a tumor (number of the tumor cells making it), at a cut begin treatment. Morfol. options of a tumor of the same localization have different sensitivity to antineoplastic means. So, small-celled cancer of a lung, nek-ry forms of angiosarcomas of soft tissues, Ewing's sarcoma have high sensitivity to antineoplastic means. The adenocarcinoma and planocellular cancer of a lung, a liposarcoma and fibrosarcoma of soft tissues, an osteosarcoma are insensitive to chemotherapy. It is noticeable the previous courses of chemotherapy or radiation therapy can change (to lower or less often to raise) sensitivity of a tumor to these means (see). Efficiency of medicinal treatment of tumoral diseases is influenced also by age and a yole of the patient, a condition of immunity and the general condition of an organism. Nek-ry malignant tumors have higher sensitivity to antineoplastic means at patients at young age and smaller — in elderly. At a serious general condition of patients efficiency of chemotherapy with below *' etsyatsya that is connected, first of all, with the expressed disturbances of processes of metabolism and delay of removal of drug from an organism.

Because antineoplastic drugs are, as a rule, rather toxic and possess a number of undesirable side effects, during the carrying out X. the lake needs to estimate its efficiency, using objective indicators. Treat those, naira., reduction of the sizes of a tumor, decrease in level of a chorionic gonadotrophin in blood at a horionepitelioma (see. A trophoblastic disease), normalization of a picture of blood and marrow at hemoblastoses (see) and other indicators (markers), specific to separate tumors. Objective assessment of action of antineoplastic means allows to replace timely in the absence of positive effect them with others or to cancel.

The nature of collateral manifestations depends on drug, a way of its introduction and the used doses. Collateral influence of antineoplastic means often appears the limiting factor at their use. At nek-ry options of use of separate antineoplastic drugs the possibility of development of side effects is reduced to a minimum and respectively control is rather just exercised that allows to carry out chemotherapy on an outpatient basis.

Many side effects are similar at different drugs, separate antineoplastic means cause specific side reactions. To the risk factors causing more frequent and heavy complications including and during the use of optimum doses of antineoplastic drugs and the mode of their use, belong: advanced

age of the patient when reserve opportunities of an organism are lowered (at elderly pulmonites after treatment by Bleomycinum, complications meet from cardiovascular system after use of adriamycin more often, etc.), a cachexia, disturbances of water and electrolytic exchange at massive exudates in serous cavities (pleurisy, ascites), the expressed abnormal liver functions, kidneys, exhaustion of reserves of a hemopoiesis as a result of the previous courses of chemotherapy, radiation therapy or hron. infections, hypoproteinemia (hl. obr., hypoalbuminemia). Depending on specific features of toxic action the cytostatics and ways of his metabolism (preferential allocation with bile, urine etc.) this or that ?faktor of risk gains the leading value. Mark out the side effects caused by toxic {cytostatic) effect of drugs: local irritative deyst

Viy (phlebitis, dermatitis, etc.), system complications (oppression of a hemogenesis, dispeptic frustration, damage of skin, disturbance of reproductive function, nevrol. frustration, an abnormal liver function, kidneys and other bodies, an immunodepressive effect with development of an intercurrent infection, embrio-toxic and oncogenous action). The immune imbalance, in turn, can lead to allergic and autoimmune reactions (see the Allergy, And at that an allergy).

On terms of emergence side effects conditionally subdivide on direct, the next and delayed. To direct, shown at once or within the first days, belong: nausea, vomiting, diarrhea, fever, hypotensive syndrome. The next are shown within 7 — 10 days: oppression of a hemogenesis, dispeptic syndrome, nevrol. and autoimmune disorders, toxic defeat of separate bodies. The delayed side effects are shown in several weeks and more after the end of treatment. So, Myelosanum, Chlorbutinum, rubomitsin, etc. can cause blood clot to an otsitopeniye (see), Vincristinum — a polyneuritis. (see). Such side effects of X. the lake as hepatitis (see) and myocarditis (see), also more often are delayed.

On degree of manifestation of a complication of X. lakes subdivide into lungs (reversible without additional to lay down. died also the terminations of chemotherapy), moderately severe (demanding additional to lay down. died without the termination of chemotherapy) and heavy at which the termination of chemotherapy and intensive treatment is necessary.

Assessment of the side effects caused by antineoplastic means requires systematic inspection of patients (blood tests, an ECG, definition of a functional condition of a liver, kidneys, etc.). In nek-ry cases there is a need for treatment of complications of chemotherapy (hemotransfusion or its components, use of stimulators of a blood formation, correction of water and electrolytic balance, etc.).

According to indications, observance of philosophy of chemotherapy the increased possibilities of modern medicinal therapy of patients onkol allow to use use of antineoplastic means more stoutly. diseases. The clear positive effect provides use of chemotherapy in the preoperative period at suffering from cancer ovaries, a mammary gland and in the postoperative period after radical operations for a breast cancer, low differentiated carcinoma of the stomach, an osteosarcoma, Vilms's tumor at children and some others.

Search of ways of increase in efficiency of X. the lake is conducted in the different directions. Of them creation of the new, more selectively acting on tumor cells drugs for monochemotherapy, development of methods of the combined treatment by two and more antineoplastic means, optimization of techniques of use of drugs (dosing, the mode of introduction), improvement of chemotherapy as link or stage of the complex and combined treatment of tumors, use of other pharmaceuticals for the purpose of decrease in side effect of antineoplastic drugs, etc. are main. Much attention is paid to studying of mechanisms of effect of drugs, their pharmacokinetics (see) and pharmacodynamics (see), on a basis to-rogo can be developed rational methods of use of the known drugs and ways of creation of new effective antineoplastic remedies are defined. Special importance is represented by a problem of overcoming the natural and acquired resistance of tumors to cytostatics, and also a research of opportunities of definition of individual sensitivity of new growths to antineoplastic drugs as a rationale of increase in efficiency of chemotherapy.

By means of chemotherapy treatment of patients of a horionepite-liomy uterus, Berkitt's tumor, a seminoma of a small egg, a lymphogranulomatosis, a carcinoma cutaneum of the I stage and children with an acute lymphoblastoid leukosis is possible. Use of antineoplastic means by the patient with acute leukoses, erythremia, multiple myeloma allows to achieve in considerable number of cases remission, and at Ewing's sarcoma, a breast cancer, a prostate, an endometria, small-celled cancer of a lung, a lymphosarcoma, at children with Vilms's tumor and a rhabdomyosarcoma — to increase life expectancy.

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M. JI. Gershanovich, BB. H. Sokolov,

A. B. Syrkin.

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