Chemotherapy action

Cytostatic drugs act on all living cells - neoplastic and normal - proportionally to the speed of growth and their division. They act the best in case of these tumours, which speed of growth is big, bigger than normal cells.

In healthy human organism cells of hemopoietic system and epithelium of gastrointestinal track divide the fastest. Only a few tumours exceed the dynamics of growth, i.e. some acute leukaemias and some tumours of lymphatic system. In case of pharmacological treatment of this type of tumours, effect of therapy is the fastest and rarely leads to destruction of normal cells. Majority of tumours grows slower than normal cells of bigger dynamics of division. That is why chemotherapy is connected z risk of reversible destruction of normal cells. The most exposed on destruction are bone marrow cells, intestinal mucous membranes, skin, oral cavity and also hair and nails.

Drugs used in chemotherapy

Cytostatic drugs can be divided into groups according to two criteria:

According to mechanism of action:

1. Alkylating agents - agents with active radicals, binding with important cell structures.

2. Antimetabolites - agents, which after incorporation into important for the cell’s life structures, create end products, which cannot serve normal functions.

3. Antineoplastic antibiotics - substances of organic origin, the most frequently derived from bacteria or fungi of cytostatic action.

4. Mitotic toxins - agents, which bind with mitotic spindle of cell, prevent its division into two derivative cells.

5. Other agents – salts of heavy metals, protein synthesis inhibitors, enzymes.

According to the phase of mitotic division, in which act:

1. Cycle dependent and phase specific cytostatic drugs - drugs that act in specific phase of cellular phase, characteristic for the fact, that increase of dose causes growth of percent of destroyed cells - to certain level. Than no, because cells, which are going to be defended are in different phase of development. The following drugs are intended for the certain phases:

• PHASE G1 asparaginase, corticosteroids;
• PHASE S: cytarabine, fludarabin, doxorubicin, gemcitabine, capecitabin, hydroxyurea, metotreksat, mercaptopurine, procarbasine, mercaptopurine, thioguanine;
• PHASE G2: bleomycin, irinotecan, mitoxantrone, topotecan;
• PHASE M: alkaloids derived from periwinkle (Vinca rosea) - vinorelbin, vinblastin, vincristin; podofilotoxin derivatives - etoposide, teniposide; taxans – paclitaxel, docetaxel.

2. Cycle dependent and phase non-specific – drugs that act on cells in division cycle independently from the phase of cycle. They are characteristic for presence of linear dependence between dose and effect (increase of dose causes constant increase of percent of destroyed cells). These drugs are nitrogranulogen, busulphan, chlorambucil, nitrosourea derivatives: carmustine, lomustine.

3. Cytostatic drugs acting independently from the division cycle, destroying cells independently from the sate of their development. These are: cisplatin, carboplatinum, cyclofosfamide, ifosphamide, melphalan, dacarbasine, anthracyclines (doxorubicin, daunorubicin, dactinomycin), alkylating drugs. Term “alkylating” derives from Chemistry and determines type of bonds in important molecules for the cells life - DNA, RNA, proteins, that originate under influence of drug and, in effect, lead cells to death.

Strategy

In treatment the most frequently a few cytostatic drugs are simultaneously used, which differ in mechanism of action and toxicity. Each drug is to act on different life phase of cellular cycle.

Use of rules of cellular kinetics helps also to create programs of multidrug chemotherapy. Established benefits from using polichemotherapy are: maximal destruction in range of possible toxicity to accept, wider spectrum in heterogenic tumours (composed of different subpopulations of neoplastic cells), prevention of resistant to cytostatic drugs cell lines development.

Basic rules doboru and kojarzenia cytostatics in programmes of multidrug chemotherapy is activity of proper drugs in monotherapy, different mechanism of action (additive/synergistic), different profiles of toxicity (maximal doses), optimal schemes of administration and different resistance (cytostatics without cross irresistance).

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