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Chemotherapy is a method of treating malignant neoplasms. Cytostatic drugs are used during chemotherapy. Their task is to destroy intensively dividing cancer cells. How does chemotherapy work? What are the types of chemotherapy and what are the side effects?

Chemotherapy in the treatment of malignant neoplasmsis designed to destroy rapidly dividing cancer cells, but it should be remembered that rapid divisions also apply to normal cells that build some tissues of our body, such as the epidermis , intestinal epithelium or bone marrow. Due to the fact that the action of cytostatics is indiscriminate, the use of chemotherapy, in addition to its therapeutic effect, is associated with the occurrence of many side effects.

Chemotherapy - types

We divide chemotherapy into radical, inductive, complementary and simultaneous.

  • Radical chemotherapyaims to completely eliminate cancer cells from the body. It is used in the treatment of chemosensitive and chemo-curable neoplasms, such as acute leukemias, lymphomas or some solid tumors (e.g. testicular cancer).
  • Induction (neoadjuvant) chemotherapyis used before another radical procedure - most often surgery. The effect of its use is to reduce the mass of the tumor, which allows for its more effective removal. In addition, it reduces the risk of spreading, as it destroys any micro-metastases. The advantage of this type of chemotherapy is the possibility of direct assessment of its effectiveness - microscopic examination of the tissues of the removed tumor allows the assessment of the degree of damage to neoplastic cells, while the degree of tumor regression is assessed in a clinical examination or imaging tests.
  • The most commonly used chemotherapy after radical surgery isadjuvant chemotherapy( adjuvant ). It serves to destroy micrometastases that may have remained in the body. Its use depends on the prognostic factors specific to the tumor with a specific location and the predictive factors that determine the sensitivity of a particular tumor to a given chemotherapy regimen.
  • Chemotherapysimultaneousis usually performed simultaneously with radical radiotherapy. As a result of its use, the sensitivity of cancer cells to ionizing radiation increases. This is done mainly by synchronizing their cell cycle, bringing the cancer cells into the phase of the cycle when they are most susceptible to radiation therapy. An additional benefit of using concurrent chemotherapy is the reduction of the risk of possible tumor spreading.

Chemotherapy - breakdown of cytostatics

Cytostatics, depending on the phase of the cell cycle in which they act on cancer cells, can be divided into two groups -phase-dependent drugsandphase-independent drugs . The use of drugs that depend on the phase of the cell cycle shows the greatest benefits when using divided doses. This means that the drug used acts only on a group of cancer cells that are currently in a specific phase of the cell cycle. As cancer cells are usually at different phases of the cycle at a particular time point, the efficacy of a single phase-dependent drug used is limited to only a fraction of the proliferating cells.

  • Drugs that depend on the S phase of the cell cycle are antimetabolites (e.g. cytarabine, 5-fluorouracil).
  • Phase M uses spindle poisons (e.g. vincristine, vinblastine), podophyllotoxin derivatives (e.g. etoposide) and taxoids (e.g. docetaxel, paclitaxel).
  • Asparaginase is used in phase G1.
  • Bleomycin, irinotecan and topotecan in G2 phase.

It is worth remembering that there is alsocomplex chemotherapy( polychemotherapy ), in which several drugs are used simultaneously that act in different phases of the cell cycle . Phase-independent drugs are alkylating drugs such as cisplatin, carmustine and chlorambucil. Their effectiveness depends only on the size of a single dose. Another division of cytostatics takes into account the mechanism of their action. On its basis, the following can be distinguished:

  • alkylating drugs
  • antimetabolites (e.g. methotrexate, 5-fluoruracil)
  • monoclonal antibodies (e.g. alemtuzumab)
  • tyrosine kinase inhibitors (e.g. erlotinib)
  • hormonal drugs (e.g. tamoxifen)
  • drugs of natural origin

The latter include:

  • anti-cancer antibiotics (e.g. doxorubicin, bleomycin)
  • podophyllotoxin derivatives (e.g. etoposide)
  • spindle poisons (e.g. vincristine, vinblastine)
  • enzymes (e.g.asparaginase)

Chemotherapy - the most commonly used cytostatics

Alkylating drugs

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 as monotherapy and polytherapy of such cancers as leukemia, lymphatic system tumors and organ tumors (including breast cancer, lung cancer, testicular cancer, ovarian cancer).

Antimetabolites

These are drugs that depend on the cell cycle phase, 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.

Cytotoxic antibiotics

The action of drugs from this group depends 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 neoplastic cell membrane. First and second generation anthracyclines and actinomycins are used in chemotherapy. An example of the 1st generation anthracycline is daunorubicin, which is used in the treatment of acute lymphoblastic and 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.

Podophyllotoxin derivatives

This group of drugs includes etoposide and teniposide. Their action is based on inhibition of topoisomerase II, resulting in an interruptionThe process of replication of the genetic material of the neoplastic cell and its subsequent death. Etoposide is mainly used in the treatment of acute myeloid leukemia, non-Hodgkin's lymphomas, small-cell and non-small-cell lung cancer, testicular cancer, Hodgkin's sarcoma and Ewing's sarcoma. Teniposide is administered in childhood acute lymphoblastic leukemia and small cell lung cancer.

Spindle poisons (mitotoxins)

These drugs interfere with the division of the cell nucleus which precedes whole cell division, resulting in the death of the cancer cell. This group includes compounds of plant origin such as vinca alkaloids, taxoids, and camptothecin derivatives. Vinblastine is an example of vinca alkaloids, 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.

Enzymes

A special enzyme used in chemotherapy is asparaginase, which breaks down the amino acid asparagine into aspartic acid. Many cancer cells have an increased demand for asparagine while losing the ability to produce it from aspartic acid. When asparagine is broken down by asparaginase and when it cannot be synthesized, cancer cells die.

The cells lacking the ability to synthesize asparagine include some neoplastic cells originating from the hematopoietic system, which justifies the administration of asparaginase in the therapy of leukemias and lymphomas. However, it should be remembered that a significant limitation in the use of this enzyme is the rapidly developing resistance to it.

Chemotherapy - side effects

The use of chemotherapy is associated with many side effects that are caused by damage to the tissues and organs of the patient that eliminate these drugs.

Common side effects of cytotoxic drugs include bone marrow damage, which leads to leukopenia resulting in impaired immunity and an increased risk of infection, thrombocytopenia with bleeding, and anemia.

In addition, chemotherapy can cause:

  • damage to the gastrointestinal mucosa, which is manifested by malabsorption and diarrhea
  • damage to the hair follicles, resulting in hair loss
  • liver damage, leading to liver fibrosis and cirrhosis

The side effects of cancer treatment include damage to the kidneys, gonads, impaired wound healing, andgrowth retardation in children.

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:

  • hyperkalemia
  • hyperphosphatemia
  • hypocalcemia
  • hyperuricemia
  • kidney failure

Unfortunately, the use of cytostatic drugs favors the emergence of secondary neoplasms over the years. There is also a breakdown of side effects, taking into account the time they appear from the chemotherapy cycle:

  • acute (immediate): nausea and vomiting, allergic reactions
  • early (4-6 weeks): bone marrow suppression, gastroenteritis, hair loss
  • delayed (several to several weeks): pulmonary fibrosis, kidney damage, cardiomyopathy, neuropathy
  • late (distant, months-years): gonadal damage, secondary neoplasms
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Category:

Oncology