Cytotoxic drugs in chemotherapy

Cytotoxic drugs

Cytotoxic drugs

Cytotoxic drugs



Traditional cytotoxic chemotherapy, which damages the DNA of cells, affects many normal cells in addition to malignant cells. Antimetabolites, such as 5-fluorouracil and methotrexate, are cell cycle-specific and have a non-linear dose-response relationship. Other chemotherapeutic agents (for example, crosslinking with DNA, also known as alkylating agents) have a linear dose-response relationship, destroy more tumor cells, and are more toxic with increasing doses. At high doses, alkylating agents cause bone marrow aplasia, which requires bone marrow transplantation to restore hematopoiesis.


Monotherapycan lead to cure of certain malignant diseases (for example, hairy cell leukemia, choriocarcinoma). However, usually multicomponent regimens contain drugs with different mechanisms of action and different toxicity, which increases the possibilities for the destruction of tumor cells,reduces drug toxicity and the likelihood of drug resistance.


These regimens can provide high cure rates (for example, in acute leukemia, testicular tumors, Hodgkin's lymphoma, non-Hodgkin's lymphoma with less effectiveness in solid tumors such as small cell lung cancer and nasopharyngeal cancer). Multicomponent regimens of chemotherapy are usually prescribed in the form of repeated cycles with a fixed combination of drugs. Intervals between cycles should be as short as necessary to restore the function of normal tissues. Prolonged infusion with the use of certain drugs that are specific to the cell cycle (for example, 5-fluorouracil) may contribute to a greater death of malignant cells.


For each patient, it is necessary to evaluate the toxicity of the regimen and its possible efficacy. The function of target organs should be assessed before prescribing chemotherapeutic drugs with organ-specific toxicity (for example, echocardiography prior to doxorubicin). Modification of doses of drugs or exclusion of some of them may be necessary inpatients with chronic lung diseases (bleomycin), renal insufficiency (methotrexate), liver dysfunction (taxanes).


Despite precautions, adverse effects are a common result of cytotoxic chemotherapy. The most striking are the tissues that have the shortest cell cycle: bone marrow, hair follicles and the epithelium of the gastrointestinal tract.


Imaging studies (CT, MRI, PET)often performed after 2–3 cycles of chemotherapy to assess the response to treatment. If there is an explicit response, therapy continues. If the tumor progresses, despite the ongoing treatment, the regimen is amended or discontinued therapy. If the disease remains stable during chemotherapy and the patient tolerates the treatment satisfactorily, it must be understood that the disease will eventually progress.


Hormonal therapy.In hormone therapy, hormones that are agonists or antagonists for a malignant tumor are used. This treatment can be used as monotherapy or in combination with other types of antitumor therapy.


Hormonal therapy is especially effective in prostate cancer, which needs testosterone for growth. Other malignant tumors that have hormonal receptors on the surface of cells (breast cancer, endometrial cancer) can often be treated with hormone antagonist medications or hormonal ablation.


The use of prednisolone, glucocorticosteroid is also considered as hormonal therapy. These drugs are often used to treat lymphomas, lymphocytic leukemia, multiple myeloma.


Biological response modifiers- Interferons are proteins that are synthesized by the cells of the immune system, as a physiological immune defensive response to foreign antigens (viruses, bacteria, other foreign cells). In pharmacological doses, they are able to alleviate the course of malignant tumors, including leukemia leukemia, chronic myelogenous leukemia, locally progressing melanoma, metastatic kidney-cell carcinoma, Kaposi's sarcoma. Toxic effects of interferon include weakness, depression, nausea, leukopenia, chills, fever, myalgia.


Interleukins, primarily lymphokine IL-2, produced by activated T cells, can be used in metastatic melanomas and can provide a significant reduction in symptoms in renal cell carcinoma.


Means affecting the differentiation of tumors.These agents induce the differentiation of malignant cells. Trans-retinoic acid is a highly effective agent in the treatment of acute promyelocytic leukemia. Other agents from this class, including phenylbutyrate, phenylacetate, arsenic compounds, vitamin D analogues, a hypomethylated deoxyazatidine agent, are currently being studied. When used as monotherapy, these drugs have a temporary effect, but their role, both in prevention and in combination with cytotoxic drugs, is encouraging.


Antiangiogenic agents.Solid tumors produce growth factors that form new blood vessels that are needed to maintain tumor growth. A number of drugs that inhibit this process are currently available. Thalido-mid has anti-angiogenic properties, among other effects.Bevacizu-mab (Avastin) is a monoclonal antibody to vascular endothelial growth factor (VEGF) and is effective in kidney cancer and colon cancer.


Signal transduction inhibitors.Many epithelial tumors have mutations that activate signaling pathways that contribute to their indomitable proliferation and lack of differentiation. These mutations affect growth factors and proteins that transmit signals from growth factor receptors on the cell surface. Two such drugs, imatinib (a VG-AY inhibitor of tyrosine kinase in chronic myeloid leukemia) and erlotinib (an epidermal growth fattox receptor inhibitor), are now routinely used in clinical practice. Other signaling pathway inhibitors are being studied.


Monoclonal antibodies.Monoclonal antibodies directed against unique tumor antigens demonstrate some efficacy in the treatment of neoplastic diseases. Tras-tuzumab, an antibody directed against a protein called Heg-2 or Erb-B2, in combination with chemotherapy is effective in metastatic breast cancer.Antibodies against CD-antigens (CD 20 and CD 33) expressed on malignant cells are used to treat patients with non-Hodgkin's lymphoma (rituximab-anti-CO20 antibody) and acute myeloblastic leukemia (gemtuzumab-antibody associated with a strong toxin).


The effectiveness of monoclonal antibodies can be enhanced by attaching radionuclides to them. One of these remedies, ibritumomab, is used in the treatment of non-Hodgkin's lymphoma.

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