Antineoplastic agents

Antineoplastic drugs used for the treatment of malignant tumors. Drug therapy is not a substitute for surgical and radiation treatments and supplements them and only under certain tumor diseases can be used as the only method of treatment, such as leukaemia, chlamydia, retikulosarkomatose, multiple myeloma, horionepiteliome of the uterus.
Anticancer drugs, have received practical application in Oncology, divided into the following groups: 1) hormones (sex hormones, corticosteroids);
2) alkylating agents - hloretilaminam (embihin, nowambien, sarkolizin, Copan, migranal, November, hlorbutin, cyclophosphamide), ethylenimine (tiofosfamid, dipin, titipan, spirutein, benzotef, perbenzoate), methanesulfonate (mielosan), epoxides;
3) antimetabolites - purine antagonists (6-mercaptopurine), pyrimidine antagonists (5-fu), antagonists folic acid (methotrexate); 4) substances of plant origin - Vinca alkaloids (vinblastine, vincristine), kolhamin; 5) antineoplastic antibiotics (actinomycin C and D, hrisomallis, olivomycin, bruneomitsin, rubomycin); 6) other drugs (natulan, ortopeda DDD).
The main condition ensuring the antitumor effect, is the predominant compared with normal tissue accumulation of drugs (except hormones) in the tumor.
Modern antitumor substances do not have the selective and therefore have to enter their high doses, although the difference between the maximum therapeutic and minimal toxic dose is less than most other drugs. In this regard, in anticancer drug therapy, often there are side effects and complications. They are expressed in inhibitory influence on the blood-forming tissue (lakopenia, thrombocytopenia), damage of mucous membranes of digestive tract diseases (stomatitis, diarrhea), nausea, vomiting, dermatitis, inhibition of spermatogenesis, violation of the ovulatory cycle and other
Given the high toxicity of anticancer drugs, an obligatory condition for their application is the strict observance of instructions for use and constant monitoring of their portability, the dynamic monitoring of the indications of the number of leukocytes and platelets in the peripheral blood, the first indications of damage of mucous membranes of digestive tract, etc.
Contraindications to the use of anticancer drugs: leiko - and thrombocytopenia, severe insufficiency of parenchymatous organs (liver, kidneys) and so on
Methods of introducing various anticancer drugs. Substances that are only entered vnutrisosudistoe, when getting under the skin cause necrosis (embihin, nowambien, vinblastine). Other drugs can be administered intravenously and intramuscularly (cyclophosphamide, thiotepa).
There are medications that are applied oral (mercaptopurine)and those that use of parenteral and oral (sarkolizin, cyclophosphamide, methotrexate).
As a rule, the use of anticancer drugs carried out by a doctor-specialist and under its control.

Antineoplastic agents - drugs used for medical treatment of malignant tumors. Antineoplastic agents belong to different classes of chemical compounds have different mechanisms of action.
The largest group is an alkylating drugs action that consists in merging a matter of the place vacated the valency of the carbon atom to the most important integral parts of the cell's DNA, RNA, proteins and phospholipids. Assume that due to the accession of the drug to the two nearby points of DNA bursting of the high-polymeric molecules into smaller parts, resulting DNA may not exercise their functions during mitosis, the transmission of genetic information and as a regulator of protein synthesis. Consequently, and also due to a breach of energy tumor cells lose their viability. Side effect alkylating substances consists mainly in the oppression of blood, which is based on the same process chemical reactions with DNA undifferentiated cells myeloid and lymphoid series. Yet many alkylating substances have known selective action on some malignant tumors, i.e., affect them more severely than blood-forming tissue.
The first drug alkilirutm action was embihin - hydrochloride methyl-di-(2-chloroethyl)amine (synonym:HN2, Dichloren, Mustargen, Dimitar). Its therapeutic effect with chlamydia, chronic leukemia, retikulosarkoma was first established by the American authors. In the USSR embihin was replaced close to his drug novamaina (see), with the same therapeutic effect, but milder side effects. The preparation is applied so far in the treatment of Hodgkin's disease and chronic lymphocytic leukemia.
Japanese authors proposed the preparation of nitrogen, which monoxide embihina. The drug is used in Japan and some European countries. Austrian scientists shown that the systematic use of nitramine after surgical removal of lung cancer recurrence percentage decreases.
With chlamydia, chronic leukemias, and retikulosarkome also effective hlorbutin (chlorambucil), Copan, migranal. The first two convenient that are used inside tablets.
Dopan - domestic original drug, which is a 4-methyl-5-di-(2-chloroethyl) aminouracil. It is applied in one dose of 8-10 mg (4-5 tablets) once in 5 days. The total dose is 50 - 80 mg. Noted side effects - nausea, sometimes vomiting, oppression blood. The treatment ends with the fall in the number of leukocytes in the blood to 3000. To prevent nausea and vomiting it is recommended to use dopan after dinner and overnight give Nembutal or chlorpromazine.
Migranal proposed in Hungary and is a dihydrochloride 1,6-di-(chloroethyl)-amino-1,6-dioximines. Used intravenously in a dose of 100 mg a day. Total dose for a course of 500-1000 mg
It is proved that using novamaina and dopana with the right and proper treatment is begun early stage of infection can be obtained positive remote results of the treatment (the life expectancy of 5 and 10 years from the treatment start).
In the USSR offered the drug sarkolizin (chlorethylamines phenylalanine), synthesized in England. Sarkolizin (see) was the first drug in a new group in which the media alkylating (chlorethylamines) group is the metabolite (essential amino acid). Action spectrum of sarcolysin differs from its predecessor drugs. Sarkolizin effective in metastatic seminomy, multiple myeloma, retikulosarkoma soft tissue and bone, cancer of the esophagus (together with kolhamina), melanoma (application of the method of perfusion), cancer of the ovary (with intra-abdominal introductions). In Germany invented the drug Endoxan (cyclophosphamide), which also has a fairly wide spectrum of action; by itself, the drug inactive, but becomes an active connection in the body. Endoxan activated mainly in the liver. Used with chlamydia, chronic and acute leukemia, lymphoreticulosis, lung cancer, breast cancer and ovarian cancer. Cyclophosphamide has a relatively weak side effects and well tolerated.
Close to di-(2-chloroethyl)amines mechanism of action the group of alkylating agents are ethylenimine. These include the drug TEM (TET), triethylenediamine. He has the effect of chronic lymphocytic leukemia, Hodgkin's lymphoma, ovarian cancer, and lung. In the USSR TEM was not implemented due to the existence of side effects. Timidin (see), proposed in the USSR, used mainly in ovarian cancer. In Germany developed etilizotiouroniu benzoquinone - E-39, A-139 and triniman. They are effective in chronic leukemias, Hodgkin's disease and some other malignancies.
A special group of ethylenimine are etilanfetamina. The main representative is thio-TEF [tiofosfamid (see)], which is used when breast cancer, ovarian and other cancers, e.g. in combination with surgical treatment of lung cancer). In the USSR proposed and applied ethylenimine: benzoate (see) - mainly in ovarian cancer, dipin and tidied (see) - with leukemia.
Dipin - original domestically produced preparation, which is a 1,4-di-[N, N'-(dietilen)-phosphamide] piperazine. Used intravenously in a dose of 10-15 mg a day for a total dose of 200 mg Described therapeutic effect dipina not only with leukemia, but when vaginal cancer metastases in the lungs.
To the class of alkylating substances refers to mielosan (see), otherwise, mileran proposed in England representative of sulfonamidnami. Mielosan deserve General recognition as the medication is most effective in chronic myeloid leukemia.
The second important group of anticancer drugs are so-called antimetabolites connection involved in the metabolism because of its resemblance to a normal exchange participants - metabolites. Because of this similarity antimetabolites can take on the active sites of enzymes places destined for metabolites, and form with apparments or coenzyme more or less durable complex. As a consequence, the corresponding enzymatic reaction is inhibited (at some stage). The bond strength of antimetabolite with ferment determines the nature of his actions.
The first antimetabolite, found practical application, was aminopterin (4-amino derivatives of folic acid).
Later produced a much more effective amethopterin (methotrexate). These drugs inhibit the synthesis of nucleic acids in the cells. Initially installed their efficacy in acute leukaemia in children. In the future, the observed effect of methotrexate in the metastasis of cancer chorionepithelioma into the lungs. With long-term intra-arterial infusions of methotrexate can cause regression of squamous cell cancers (cervical, head and neck tumors). The second product group antimetabolites - 6-mercaptopurine - is the most effective in the treatment of acute leukemia and can cause disease remission not only children but also adults. 6-Mercaptopurin used inside tablets daily 2.5 mg/kg for 3-8 weeks or more before the onset of remission. If after 4 weeks of starting treatment improvement does not occur and there are no side effects, the dose gradually increased to 0.5 mg/kg In the treatment of acute leukemia 6-mercaptopurine is used in combination with other protivoopujolevami drugs and prednisolone. The third antimetabolite-5-fu - it has a wide range of antitumor activity. It inhibits the synthesis of deoxyribonucleic acid and joining in ribonucleic acid, making it a "fake". In the tumor cells lose their viability.
Unlike alkylating agents, 5-fu may be effective in the primary adenocarcinomas a number of organs: stomach, pancreas, liver, colon and rectum, breast, ovary. Fluorouracil enhances the effect on tumor ionizing radiation and therefore, in combination with radiotherapy has the effect of lung cancer. Fluorouracil is very important anticancer drug, as it may provide a therapeutic effect in the most common tumors (cancer of the stomach and others).


The third group of products - antineoplastic antibiotics. One of them received the application of the aktinomitinov (see) C and D. the First gives effect in the early stages of infection. Russian version is called aurantia. Actinomycin D is effective in cancer chorionepithelioma (especially in combination with methotrexate), when the tumor metastases kidneys (Wilms'), and in children in combination with radiotherapy, and in some other tumors. When horionepiteliome very active domestic antibiotic hrisomallis.
Antibiotic mitomycin C, containing an alkylating group, according to a Japanese authors, has a positive effect in breast cancer, stomach and lung metastases osteogenic sarcoma. Close to antibiotics domestic drugs (Crutzen and neocid) used in the treatment of advanced stages of malignant tumors as symptomatic funds.
The group of drugs of plant origin are kolhamin and vinblastine. Kolhamin isolated from Colchicum domestic authors. Is desaceleraciyn. When using inside a single dose of 4-5 mg a day. Kolhamin at outside applying (ointment), can cure skin cancer is only in the early stages. In combination with sarcolysin gives effect in cancer of the esophagus. Vinblastine and close to it vincristine have a positive impact with chlamydia, acute leukemia, horionepiteliome and some other malignancies. The preparation of birch fungus "chaga" is used in different tumors as symptomatic means.
The last group of anticancer drugs are hormones and hormone-like substances. Hormones act on tumor mostly not directly, but through the influence on endocrine organs and some of metabolism in the body. The first group of hormonal drugs are estrogen, i.e. the substance with the action of female sex hormones (see). To them belong sinestrol, diethylstilbestrol, estradiol, honvan (fosfestrol), estrablin etc. Used for the treatment of prostate cancer and breast cancer in older women). Assume that the effect of estrogen is via inhibition of secretion of follicle-stimulating hormone from the pituitary. The second group - androgens (substances with the action of the male sex hormone). To them belong testosterone propionate (intramuscular), methyltestosterone, methylandrostendiol, 2A-methyldihydromorphinone. They are used in breast cancer in young women. Hormones yellow body progesterone and oksiprogesterona-kapronat (delalutin) can be used in the treatment of breast cancer and uterus. The third group of hormonal drugs are corticosteroids (see), cortisone, prednisone, prednisolone, targetrotation and other Corticosteroids are used in the treatment of acute leukemia, chronic lymphocytic leukemia, Hodgkin's disease and breast cancer.
The effect produced by anticancer drugs, depends on the sensitivity of the tumor to a specific drug, the disease stage, in particular from the volume of the tumor, whether only the primary tumor, or metastasis, or both, from the General state of the organism, from the applied methods of treatment. In some patients, the effect is merely subjective and reflected in the improvement of the General condition, the pain, the other decreases the temperature decreases cough, improved cross-country ability PSP (for example, in cancer of the esophagus and stomach), but the objective indicators of the state of the tumor remains the same (symptomatic effect). The third group of patients is the reduction of the sizes (regression) tumors until the complete disappearance (the objective effect).
Most of the drugs that have the objective effect, gives it only under certain tumors localization and histological structure, and at that not all patients that depends on biochemical features of different tumors of the same body. In some cases, the drug works better on metastases than in primary tumours (for example, sarkolizin in seminoma)in non - primary tumor responds stronger (for example, cancer of the stomach in the administration of 5-fluorouracil). Get the objective effect can be very short, especially with a slight regression of tumors, and lasts from several weeks to several months. When complete regression of some tumors can be obtained lasting effect for a period of 3-5 years or more. This kind of result, conventionally referred to as clinical cure obtained, for example, as a result of application kolhamina for skin cancer, sarcolysin - in seminoma, multiple myeloma, retikulosarkoma bones, dopana - with chlamydia, methotrexate - when metastases horionepitelioma. Antineoplastic used both independently and in combination with surgery and radiation treatment. It is established that actinomycin D (hrisomallis) and 5-fluoro-uracyl potentiate the effect of ionizing radiation on some tumors. There is evidence that the use of certain drugs (Nitrogen, Endoxan, thio-TEF) after surgical removal of lung cancer decreases the percentage of relapses and metastases. Postoperative chemotherapy in other malignant tumors are insufficiently developed.
To obtain the greatest therapeutic effect is essential methods of therapy drugs. Due insufficiently high selectivity of action of existing drugs in most cases, you use the maximum tolerated dose, the achievement of which is determined by the appearance of side effects (decrease in the number of leukocytes and platelets with alkylating agents, phenomena from the side of the mouth and gastrointestinal tract when antimetabolites etc). To increase the therapeutic effect and weakening of side effects in some cases, the use of regional preparations introduction - intracavitary, intra-arterial infusion and perfusion (see Perfusion of isolated bodies). Currently, intensive work on creation of new anticancer agents. with higher selectivity and various range of antitumor activity.