Concept and Uses
Antineoplastic drugs, alone or in combination, can be used in the treatment of cancer to achieve:
- Chemo-prevention: natural or synthetic products or antineoplastic agents to prevent or suppress carcinogenesis in people highly susceptible to certain cancers.
- Cure: the destruction of all cancer cells, increasing life expectancy.
- Control: prevent or slow the growth of a tumor to prolong survival.
- Palliation: treatment of symptoms.
A series of terms describe the role of antineoplastic agents in cancer control:
- Induction: initial therapy is administered to achieve significant debulking and, ideally, complete remission of the disease.
- Consolidation/intensification: administered after induction to prolong the absence of disease and overall survival. Although consolidation therapy uses the same agents as induction therapy, intensification therapy uses agents that are not resistant to induction therapy.
- Adjuvant treatment: antineoplastic agents used in combination with another treatment modality, i.e., biotherapy, radiotherapy, or surgery, intended to treat micro-metastases and prevent local recurrence.
- Neo-adjuvant treatment: antineoplastic agents reduce the tumor size before definitive treatment.
- Maintenance therapy: long-term low-dose therapy administered to prolong the duration of remission and achieve healing.
- Primary therapy: antineoplastic agents administered as definitive treatment.
- Combination therapy: two or more agents to treat the disease.
- Myeloablative therapy prepares individuals for the transplantation of hematopoietic stem cells.
- Rescue therapy: drug agents administered after the failure of other treatments to control the disease or provide palliation.
Antineoplastic agents frequently interrupt replication at the cellular level, obstructing the synthesis of new genetic material or causing irreversible damage to DNA itself.
Although this affects normal and malignant cells, normal cells have a more remarkable ability to repair minor damage and continue living.
The greatest weakness of the malignant cells is used to achieve the therapeutic effects observed with the administration of antineoplastic agents.
The mechanisms of action of antineoplastic agents are based on the concepts of cell kinetics – cell cycle time, growth fraction, and tumor load:
The cell cycle time is the time necessary for the cell to complete a complete cycle from mitosis.
Cycle times for cancer cells vary from 24 to 120 hours, with most from 48 to 72 hours.
Those cells with shorter cycle times are more easily damaged by specific cytotoxic agents of the cell cycle phase.
The continuous infusions of these agents result in higher percentages of cell death since a more significant number of cells are exposed to the agent.
The growth fraction is the percentage of cells in the tumor reproducing (cycling).
For cancer cells, there is no difference from that of normal cells – the main difference is that cancer cells proliferate continuously.
Higher growth fractions result in cell death with agents specific to the cell cycle phase.
In tumors with most cells in G 0 or the resting phase, using cytotoxic agents not specific to the cell cycle phase results in increased cell death.
The tumor burden is the number of cells in the tumor. Tumors with a small load are more sensitive to antineoplastic agents.
As the tumor burden increases, the fraction of growth and sensitivity to systemic treatment is reduced.
It is theorized that cancer cells exposed to a specific dose of antineoplastic agents will destroy a constant percentage of cells in the tumor. This concept is known as first-order kinetics.
According to this theory, repeated therapy doses are needed to reduce the total number of cells.
The number of cells remaining after therapy depends on the previous treatment results, the time between repeated doses, and the time of tumor duplication.
Repeated treatments are administered to reduce the tumor to a small enough number of cells so the immune system can kill any remaining cells.
The pharmacodynamic properties of antineoplastic agents, including their actions and behavior in the body, define the therapeutic effects of the agent.
The effective dose should not be too high (side effects will be too severe) or too small (the tumor will continue to grow and may develop resistance).
The main pharmacological factors that affect antineoplastic actions are:
- Administration route.
Dictated by the characteristics of the individual drugs and chosen to optimize the availability of drugs. The anticancer effects can be improved with higher concentrations at the tumor site.
- Distribution of medications.
The distribution and transport of drugs within the body can affect the proportion of the free or pharmacologically active drugs in the bloodstream.
Metabolic biotransformation of antineoplastic agents includes oxidation, reduction, hydrolysis, or conjugation performed primarily in the liver.
The agents are commonly excreted through the kidneys or the liver.
- Interactions with other drugs.
The agents can inhibit or enhance the action of another, thus modifying the therapeutic or toxic effects or their inhibition or enzymatic induction.
- Drug resistance
Primary resistance refers to the lack of tumor response when agents are administered. According to the studies, secondary resistance occurs after the initial regression of the tumor.
Factors that contribute to secondary resistance include:
- Variations in the bioavailability of the drug.
- Metabolism or drug elimination.
- Tumors are possibly located in ‘sacred sites.’
- Changes in cell kinetics.
- Drug-related toxicity in the recipient organism.
- Reduction of the blood supply to cancer.
Multidrug resistance (RMF) refers to the phenomenon whereby exposure to a single drug is followed by cross-resistance to unrelated other medicines, thus causing a low effectiveness rate in the treatment provided to the patient.