Cytotoxic drugs (cytostatic drugs, cytostatics) are drugs used in chemotherapy - a method of systemic treatment of malignant neoplasms. Cytostatics are effective in killing cancer cells, but they have numerous side effects. These drugs destroy the rapidly dividing cells that build the tissues of our body, such as the epidermis, intestinal epithelium and bone marrow.

Cytotoxic drugs( Cytostatic drugs ,Cytostatics ) are used to obtain a cure or long-term remission of the disease in neoplasms with high sensitivity to chemotherapy - this is the so-called radical behavior.

In addition, cytostatics are used to extend life and / or reduce ailments and symptoms when the benefits resulting from treatment outweigh the risk of deterioration of the general condition and quality of life due to the adverse effects of particular drugs - this is the so-called palliative treatment.

  • How does chemotherapy work?

In order to reduce the risk of tumor resistance to treatment, multi-drug chemotherapy regimens with the use of cytostatics are used - most often these are 2-3 drugs, administered at 21-28 days intervals.

Cytostatics: division

Cytostatic drugs can be divided according to their chemical structure and mechanism of action, and the phase of the cell cycle in which they exert their effect.

Due to the chemical structure and mechanism of action, the following are distinguished:

  • alkylating drugs
  • antimetabolites
  • anti-cancer antibiotics
  • podophyllotoxin derivatives
  • plant alkaloids
  • taksoidy
  • camptothecin derivatives

Cytostatics, depending on the phase of the cell cycle in which they affect neoplastic cells, can be divided into two groups - phase-dependent drugs and phase-independent drugs.

  • Phase-dependent drugs

Phase-dependent drugs are active in a specific phase of the cell cycle. This means that the drug used only affects a group of cancer cells that are currently in a specific phase of the cell cycle.

Since cancer cells are usually at different stages of the cycle at a specific point in time, the effectiveness of theof a single phase-dependent drug is limited to a fraction of proliferating cells only.

For example, drugs with antimetabolic activity show activity in the S phase of the cell cycle, antitumor antibiotics in the S, G2 and M phase, and plant alkaloids and taxoids in the M phase. Podophyllotoxin derivatives and camptothecin derivatives, on the other hand, act in the G2 phase of the cell cycle.

  • Phase-independent drugs

Drugs independent of the cell cycle phase show a linear dose-effect relationship, which means that the higher the dose of cytostatic used, the greater the percentage of destroyed tumor cells. The group of these cytostatics includes drugs with an alkylating effect.

Cytostatic drugs: characteristics of the most commonly used

  • ALKILATORS

The essence of the mechanism of action of these drugs is the creation of chemical compounds with functional groups of molecules essential for the proper functioning of the cancer cell, such as DNA, RNA, enzymes and hormones with a protein structure.

It takes place through alkylation, which impairs the basic life processes of the cancer cell - mainly the biological activity of DNA.

These drugs, despite acting independently of the cell cycle phase, show the strongest activity in the period when the cell enters the S phase and synthesizes large amounts of DNA, RNA and proteins. Their cytostatic effect is most pronounced against rapidly dividing cells.

These drugs are used both in monotherapy and polytherapy of cancers such as leukemia, lymphatic system cancer and organ tumors (including breast cancer, lung cancer, testicular cancer, ovarian cancer).

  • ANTIMETABOLIT

These are drugs that depend on the phase of the cell cycle, which are active primarily in the S phase. Their chemical structure resembles chemical compounds that cancer cells use for proper functioning.

Due to the fact that a cancer cell cannot "distinguish" antimetabolites from substances that it needs, it uses them in its life cycle. This results in the formation of abnormal structures with a subsequent blockage of the cancer cell division.

Antimetabolites are the best in treating fast-growing tumors. For example, methotrexate is used to treat, inter alia, leukemias, lymphomas, breast cancer, sarcomas, gestational trophoblastic disease, and fluorouracil - in the treatment of breast cancer and cancer of many organs of the gastrointestinal tract.

  • ANTI-Cancer Antibiotics

The action of drugs from this groupdepends on the phase of the cell cycle and is based on the destruction of the DNA structure, generation of free radicals and direct damage to the cancer cell membrane.

I and II generation anthracyclines and actinomycins are used in chemotherapy. An example of a 1st generation anthracycline is daunorubicin, which is used in the treatment of acute lymphoblastic leukemia and acute myeloid leukemia.

Second generation anthracyclines (aclarubicin, epirubicin, idarubicin, mitoxantrone) are used in the treatment of acute myeloid and lymphoblastic leukemia. Additionally, mitoxantrone is used in the treatment of breast and prostate cancer.

  • SUBPHYLOTOXIN DERIVATIVES

This group of drugs includes etoposide and teniposide. Their action is based on the inhibition of topoisomerase II, as a result of which the process of replication of the genetic material of the neoplastic cell is interrupted and its subsequent death.

Etoposide is mainly used in the treatment of acute myeloid leukemia, non-Hodgkin's lymphomas, small and non-small cell lung cancer, testicular cancer, Hodgkin's cancer and Ewing's sarcoma.

Teniposide is administered in childhood acute lymphoblastic leukemia and in small cell lung cancer.

  • PLANT ALKALOIDS, TAKSOIDS AND CAMPTOTECIN DERIVATIVES

These drugs are spindle poisons (so-called mitotoxins). They disrupt the division of the cell nucleus, which precedes the division of the entire cell, which results in the death of the cancer cell.

An example of plant alkaloids is vinblastine used in the treatment of many hematological cancers, testicular cancer, breast cancer, bladder cancer, lung cancer and others, and vincristine with a similar spectrum of activity.

Paclitaxel and docetaxel belong to the group of taxoids. They are used to treat advanced metastatic breast cancer and ovarian cancer. The last group of camptothecin derivatives includes i.a. irinotecan and topotecan. They are mainly used in the treatment of colon and rectal cancer, stomach cancer, but also ovarian cancer and small cell lung cancer.

Cytotoxic drugs: side effects

The use of chemotherapy is associated with many side effects, which are caused by damage to organs and systems with the highest content of cells undergoing cell division (mucous membranes of the digestive system and respiratory system, bone marrow, gonads, skin and hair), but also damage to the tissues and organs of the patient that eliminate these drugs.

Common side effects of cytotoxic drugs include bone marrow damageleads to leukopenia manifested by impaired immunity and an increased risk of infections, thrombocytopenia manifested by bleeding, and anemia.

In addition, chemotherapy can damage the mucosa of the gastrointestinal tract, which manifests itself in malabsorption and diarrhea, damage to the liver leading to liver fibrosis and cirrhosis, and damage to the hair follicles resulting in hair loss.

The use of cytostatic drugs in the perspective of years increases the risk of developing secondary cancers.

The side effects of cancer treatment, such as kidney damage, gonadal damage, impaired wound healing, and poor growth in children should not be forgotten.

After the use of cytostatic drugs, especially in the case of acute leukemias and some lymphomas, the so-called tumor lysis syndrome. It results from the sudden breakdown of a large number of cancer cells and is characterized by disorders such as hyperkalaemia, hyperphosphataemia, hypocalcaemia, hyperuricemia, and renal failure.

There is also a breakdown of side effects according to the time they occur from the chemotherapy cycle:

  • acute (immediate)
    - nausea
    - vomiting
    - allergic reactions
  • early (4-6 weeks)
    - bone marrow suppression
    - inflammation of the gastrointestinal mucosa
    - hair loss
  • delayed (several or several weeks)
    - pulmonary fibrosis
    - kidney damage
    - cardiomyopathy
    - neuropathies
  • late (distant, months-years)
    - gonadal damage
    - secondary occurrence of tumors

Category:

Oncology