Beginning of chemotherapy in cancer II. It dates back to the years of World War II. The first cytotoxic drug,
Nitrogen mustard, began to be used in hematological malignancies in the 1950s after it was observed incidentally that it suppressed the bone marrow.
Then, other
alkylating agents, antimetabolites, vinca alkaloids and antibiotics came into use.
Single agent chemotherapy applications were followed by combination chemotherapies over the years.
The role of chemotherapy in cancer treatment is especially The new generation discovered in recent years has become more evident with the introduction of more effective cytotoxic agents. In the past 10-15 years, a better understanding of cancer biology in parallel with the developments in the field of molecular biology has led to the introduction of biological and targeted agents into the clinic. While the use of newer
generation treatment agents increases the effectiveness of chemotherapy,
rational use of cytotoxic agents in the correct indications will increase the clinical
benefit to patients.
p>CELL CYCLE
The time from the beginning of one mitosis to the next mitosis is called the cell cycle and consists of 5 phases
. In normal cells, the cell cycle is approximately 2-3 days. The cell cycle begins with the G1 phase in the postmitotic
period. In the G1 phase, enzymes to be used for DNA and RNA synthesis and the production of other proteins required in this process are synthesized. DNA synthesis takes place in the S phase following the G1 phase, and then the transition to the premitotic stationary G2 phase, in which RNA synthesis takes place.
The cell cycle ends with division in the mitosis phase. The majority of cancer cells gather in the G0 phase, and these cells do not proliferate actively. For this reason
The effect of chemotherapeutic drugs on these cells is practically negligible.
TUMOR CELL KINETICS
Cancer cells have the ability to grow uncontrolled. Disruption of cell differentiation
(dedifferentiation), infiltration and invasion ability, and metastasis to distant organs
are other characteristics of tumor cells.
Uncontrolled growth is based on genetic characteristics. Chromosomal cytogenet These anomalies may cause
activation of oncogenes or inactivation of tumor suppressor genes.
Growth inhibition (contact inhibition) in normal body tissues is not seen in tumor cells
and as a result, uncontrolled proliferation occurs. emerges. The reason for the growth of the tumor mass
is that the balance between cell proliferation and death in normal tissues
is disrupted in favor of proliferation in cancerous tissues.
Tumor growth depends on various factors. Growth fraction, duration of the cell cycle
, number of cells forming the tumor and death rates in these cells are factors that affect tumor growth.
With treatment, only some of the cells, not all of them. Since the patient dies, chemotherapy must be administered in repeated cycles. Since normal tissues are also affected as a side effect, it is not possible to give high doses of chemotherapy that could kill the entire tumor.
If the same percentage of cancer cells can be killed in each cycle, it can be considered that, theoretically, the cancer should be destroyed after a certain number of cycles at some point.
However, cancer is a heterogeneous tissue. Not all cells in a tumor are equally sensitive to chemotherapy. The vascular structure of cancer, location and accessibility of cancer cells are variable. In addition, cellular sensitivity may decrease during treatment
and cancer may become resistant to cytotoxic treatment.
WHAT PURPOSE SHOULD CHEMOTHERAPY BE GIVEN?
Treatment in patients with cancer. The purpose of the chemotherapy to be given should be determined before starting. For this, the indication for giving chemotherapy in the patient must first be determined correctly.
In cases of slowly progressing, asymptomatic and non-curable tumors, in cases where it is not possible to monitor the chemotherapy response and
side effects and to treat them, or when the tumor is
/p>
If shrinkage does not bring any advantage in terms of symptoms and survival
chemotherapy should not be used.
Before chemotherapy is given, histopathological tissue diagnosis should be confirmed and disease
staging should be done. The patient's organ functions, performance status, and age should be evaluated before treatment
should be evaluated.
Chemotherapy can be applied for 4 different purposes and clinical situations:
1) Therapeutic (definitive) chemotherapy: Some malignant It is performed to provide cure (healing) for tumors
Such tumors include some childhood cancers, testicular cancers,
germ cell cancers, small cell lung cancer, hematological neoplasias (lymphoma and
acute leukemias).
p>2) Palliative chemotherapy: It is given to reduce symptoms and/or prolong life in metastatic cancers that are known to be incurable.
Applications in metastatic breast,
colon and lung cancers are the best examples of this, but these examples
can be multiplied.
3) Adjuvant chemotherapy: It is also called preventive chemotherapy among the public. It is used to destroy local
metastases that are thought to be present at the microscopic level after treatment (usually surgery); ovarian cancer, breast cancer and colorectal cancers
are the tumors for which adjuvant chemotherapy is most successful.
4) Neoadjuvant (primary) chemotherapy: Before local treatment, the tumor is usually /p> Used to reduce size; Other purposes and benefits are determining the sensitivity of the tumor to chemotherapy and organ protection. Today, it constitutes the basic element of organ-preserving treatment, especially in head and neck tumors, rectal cancers and extremity sarcomas . Its role in breast cancer is also very evident.
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