How chemotherapy works
Chemotherapy is the use of one or more anticancer (cytotoxic) drugs to damage cancer cells so they can’t grow and reproduce. Chemotherapy is most effective on cells that are actively growing and dividing. Because many cancer cells tend to grow and divide quickly, they are sensitive to the effects of chemotherapy.
All cells go through the cell cycle. This is the process by which cells divide to produce more cells. Chemotherapy drugs interrupt the cell cycle and slow down or stop cancer cells’ reproduction. Some drugs specifically affect cancer cells going through one or more phases of the cell cycle (called cell cycle–specific drugs). Others affect cancer cells in all phases of the cell cycle, regardless of whether they are dividing or resting (called cell cycle–non-specific drugs).
Although a single drug may be used to treat certain types of cancer, a combination of drugs often leads to better outcomes. The goal of combination chemotherapy is to:
- kill as many cancer cells as possible without causing too much damage to healthy cells or side effects (toxicity)
- increase the chances of killing cancer cells, regardless of where they are in the cell cycle
- lower the chances that cancer cells will develop mutations that make them resistant to certain drugs
Cancer cells may not be sensitive to one or more chemotherapy drugs. These cancer cells are referred to as resistant.
A cancer cell may be resistant to a chemotherapy drug from the beginning (called primary or natural resistance). It may also respond to a drug for a while and then stop responding (called secondary or acquired resistance).
Cancer cells are more likely to be resistant to a single drug. They are less likely to be resistant to 2 or more chemotherapy drugs used at the same time. A combination of chemotherapy drugs reduces the chance of cancer cells developing a resistance to the treatment.
If cancer cells develop resistance to one chemotherapy drug, they may also develop resistance to other drugs in the same drug family.
Some cancer cells develop resistance to drugs from several drug families. This is called multidrug resistance (MDR). MDR is a particular challenge for planning and adjusting treatment.
P-glycoprotein (P-gp) is a protein on the surface of cancer cells. P-gp acts like a pump that controls how chemotherapy drugs pass in and out of the cells. Cancer cells that make a large amount of (overexpress) this protein may block the drugs, making chemotherapy ineffective. MDR is often associated with an overexpression of P-glycoprotein.
Cancer cells respond to chemotherapy differently. Some types of cancer respond better or are more sensitive to chemotherapy than others. How well cancer cells respond to chemotherapy is called chemosensitivity.
Chemosensitivity depends on several factors, including the:
- rate of growth of the cancer cells
- Chemotherapy is most effective against cancer cells that are actively dividing.
- drug dose
- Doctors try to give a dose that will have the best possible response, while not causing serious side effects.
- If the dose is too low, it may affect cancer cells but not effectively treat the cancer.
- drug’s ability to reach cancer cells
- Cancer cells that overexpress P-glycoprotein (P-gp) may block drugs so they can’t enter the cells.
- A protective barrier between the blood and brain tissue stops potentially harmful substances from entering the brain. Many chemotherapy drugs do not cross this blood-brain barrier.
Chemotherapy is prescribed by a medical oncologistmedical oncologistA doctor who specializes in diagnosing and treating cancers using chemotherapy, biological therapy, hormonal therapy and supportive therapy.. This doctor chooses the drugs and determines the dose, schedule and length of treatment. Chemotherapy regimens depend on the:
- type of cancer
- stagestageA description of the extent of cancer in the body, including the size of the tumour, whether there are cancer cells in the lymph nodes and whether the disease has spread from its original site to other parts of the body. of the cancer
- person’s age
- person’s overall health
- types of cancer treatment given or planned
Chemotherapy drugs may not kill all the cancer cells the first time they are given. Some cancer cells will survive and continue to grow. Chemotherapy is given according to a plan or schedule designed to kill as many cancer cells as possible. Chemotherapy treatment is often repeated and is usually given at regular intervals called cycles. Each cycle of chemotherapy is usually followed by a rest period (such as several days or weeks) when no treatment is given. The rest period allows normal cells to recover.
The length, timing and number of cycles of chemotherapy a person receives depend on the combination of drugs used and the type of cancer. The medical oncologist usually sets the schedule when treatment starts. The schedule may also be determined later, based on how quickly the tumour responds to the drugs. The total course of a chemotherapy treatment is usually about 6 months, but it can range from 3–12 months.
Doctors calculate chemotherapy doses in different ways, depending on the drug or drugs to be given. Overall dose is usually based on the person’s body surface area (BSA), which is calculated using height and weight and expressed in metres squared. For a few drugs, the dose is based only on the person’s weight in kilograms.
The bodies of children and some adults process drugs differently and they may have different levels of sensitivity. After taking the BSA into account, the doctor may change dosages for children and some adults. Dosages of some drugs may be adjusted for people who:
- are elderly
- are undernourished or malnourished
- are obese
- are taking or have taken other medicines
- are receiving or have already received radiation therapy
- have low blood cell counts
- have liver or kidney disease
Chemotherapy is given at high enough doses to effectively destroy the cancer cells and cure or control the cancer, while limiting side effects as much as possible.
Very high doses of drugs can cause severe side effects, which may limit the amount of drug that can be given (called a dose-limiting factor). Sometimes the doctor will have to adjust the chemotherapy regimen to allow the person time to recover from the side effects.
Chemotherapy may be used again if cancer recurs (comes back). For some drugs, there is a limit to how much can be given (called the maximum lifetime dose) because they can affect organs, such as the heart or lungs. Once a person receives the maximum lifetime dose, the drug cannot be used again. For example, anthracycline drugs, such as doxorubicin (Adriamycin) or daunorubicin (Cerubidine), may increase the risk of heart damage and bleomycin (Blenoxane) may increase the risk of lung damage.
I’m extremely grateful to the Canadian Cancer Society for funding my research with an Innovation Grant.
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