How Does Chemotherapy Work?
Understanding how normal, healthy cells grow and divide is essential to understanding how chemotherapy works. All living things are composed of cells. Cells grow, divide, and die in a regulated fashion. The cell cycle is the process that normal and abnormal cells go through to grow and reproduce.
Five phases comprise the cell cycle:
- G0 phase—The resting phase (the cell has not started to divide). This step can last a few hours, a few days, a few years, or a lifetime. When the cell is signaled to reproduce, it moves to the next phase, G1.
- G1 phase—The cell readies to divide by manufacturing proteins necessary for reproduction. This phase lasts about 18-30 hours.
- S phase—The cell’s complement of genes made of DNA is copied so that when the cell divides, the new cell will have a copy of the genetic information. This phase lasts from 18-20 hours.
- G2 phase—Further protein synthesis occurs; this phase lasts from 2-10 hours.
- M phase—The cell splits into 2 new cells. This phase lasts about 30-60 minutes.
Normal, healthy cells go through the cell cycle in a regulated manner—as some cells are dividing and creating new cells, other cells are dying. Abnormal cells divide and reproduce uncontrollably, creating a mass of cells known as a tumor.
The cell cycle is important to chemotherapy because chemotherapeutic drugs target and disrupt different phases of the cell cycle. Most chemotherapy drugs act on reproducing cells (not those in the G0 phase). Because cancer cells actively reproduce, they are primarily targeted by chemotherapeutic drugs. However, healthy cells reproduce as well, so they too are affected by chemotherapy. This is what causes side effects. When chemotherapy is given, the doctor must find a balance between destroying the cancer cells and sparing the normal cells.
What Is Chemotherapy Used For?
Chemotherapy is given for the following reasons:
- Cure—The goal is to cure the cancer so that is disappears (is killed off) and does not return.
- Control—If cure is not possible, chemotherapy aims to control the growth and spread of the cancer.
- Palliation—If cure and control are not possible, chemotherapy is given to relieve symptoms caused by the cancer.
Chemotherapy is used to treat many different types of cancer. The type, location, and stage of the cancer as well as your general health will largely determine if chemotherapy is appropriate and which agents ought to be used. For example, adjuvant chemotherapy is considered standard treatment for breast, colon, and rectal cancers. Neoadjuvant chemotherapy has been used effectively in breast,
laryngeal, and locally advanced non-small cell lung cancers.
Brain tumors are more difficult to treat with chemotherapy because of the shielding effect of blood-brain barrier (BBB), the tumor's location inside the skull, and the lack of adequate lymphatic drainage.
What Are the Types of Chemotherapy?
Cell Cycle Phase-specific
Cell Cycle Phase-nonspecific
Chemotherapeutic drugs are classified by their pharmacologic action and their interference with cellular reproduction. They are divided into cell cycle phase-specific and cell cycle phase-nonspecific.
Cell cycle phase-specific
drugs act on cells undergoing division. Therefore they affect cells in phases G1, S, G2, or M, but not G0. Because these drugs exert their cytotoxic effects during the cell cycle, they are most effective against actively growing tumors. They are given in minimal concentrations using continuous dosing methods. Examples include the following:
- Vinca plant alkaloids
- Miscellaneous agents, such as asparaginase and dacarbazine
Cell cycle phase-nonspecific
drugs act on cells either in dividing or resting states. Because these drugs are active in all phases of the cell cycle, they may be effective in large tumors that have fewer active cells. Cell cycle phase-nonspecific drugs are usually given as a single injection. Examples include the following:
- Alkylating agents
- Antitumor antibiotics
- Hormone and steroid drugs
- Miscellaneous agents, such as procarbazine
Chemotherapy can be administered via several routes. The most common method is through an IV. Usually, a thin needle is inserted into a vein on the hand or lower arm at the onset of the treatment session and is removed at the conclusion.
Chemotherapy can also be delivered by IV through catheters, ports, and pumps. A catheter is a soft, thin, flexible tube that is placed in a large vein in the body. It remains in place as long as necessary. Sometimes the catheter is attached to a port, which is a small round plastic or metal disc placed under the skin. The port stays in place as long as necessary. A pump can be used to control how fast the drugs go into the catheter or port. An external pump remains outside the body, while an internal pump is surgically placed just under the skin.
Common IV delivery methods include:
- Central venous catheter (CVC)—Placed in a large vein, most commonly in the chest.
- Peripherally inserted central catheter (PICC)—Inserted into a vein in the arm and threaded to deeper, central veins.
- Intrathecal—Chemotherapeutic drugs are delivered directly into the cerebrospinal fluid that surrounds the spinal cord.
- Intracavitary catheter (IC)—Placed in the abdomen, pelvis, or chest.
Chemotherapy can also be delivered in methods other than IV. These include:
- Oral—The drug is given in pill, capsule, or liquid form and swallowed.
Injection—The drug is given using a needle or syringe in one of several ways:
- Intramuscularly (IM)—into the muscle
- Subcutaneously (SQ or SC)—under the skin and into the fat tissue
- Intralesionally (IL)—directly into the cancerous area of the skin
- Topical—The drug is applied to the surface of the skin.
What Adverse Effects Can Occur With Chemotherapy?
Because chemotherapy can kill healthy cells along with cancer cells, many side effects are associated with this form of treatment. The most common side effects occur in areas where healthy cells rapidly divide. These include:
- Blood cells
- Hair follicle cells
- Skin cells
- Reproductive and digestive tract cells
You may experience no side effects or just a few. The kind of side effects and how severe they are will depend on the type and dose of chemotherapy and how your body reacts. Some of the more common side effects are described below.
Fatigue, feeling tired and lacking energy, is the most common symptom experienced by people receiving chemotherapy. Fatigue from chemotherapy feels different from the fatigue that you may experience from everyday life. Chemotherapy fatigue can appear suddenly. Some people have described it as a total lack of energy, feeling drained or wiped out. The fatigue can last days, weeks, or months, but it usually goes away gradually as your body responds to treatment.
There are some things you can do to help cope with fatigue:
- Plan time to rest throughout the day.
- Take several short naps or breaks, rather than one long one.
- Try easier or shorter versions of activities you enjoy.
- Take short walks or do light exercise (with your doctor’s approval).
- Allow others to help you with daily responsibilities.
and avoid caffeine and alcohol.
- Focus on maintaining as normal a lifestyle as is possible. Continue to do what you enjoy doing, but rest as needed.
Nausea and Vomiting
Nausea and vomiting are common side effects of several chemotherapeutic agents. Chemotherapeutic drugs irritate the lining of the stomach and the first section of the small intestine (duodenum), which stimulates certain nerves that lead to the vomiting center of the brain.
Although everyone is different, certain drugs are more likely to cause vomiting than others.
Emetic Chemotherapeutic Drugs
(in high doses)
(in high doses)
(in high doses)
(in high doses)
Many things can influence the likelihood and severity of nausea and vomiting:
- Prior experience with motion sickness
- Previous bad experiences with nausea and vomiting
- Younger age
- Heavy alcohol intake
- Women of menstrual age
There are some things that can be done to help control the nausea and vomiting associated with chemotherapy:
- Drink liquids at least 1 hour before or after meals, instead of with your meal.
- Eat and drink slowly.
- Eat several small meals throughout the day, instead of a few larger meals.
- Breathe deeply and slowly when feeling nauseated.
- Avoid sweet, fried, greasy, or fatty foods.
- Rest, but do not lie flat for at least 2 hours after a meal.
- Try ginger tablets or ginger ale. Ginger has been reported to reduce feelings of nausea.
- Wear loose-fitting clothes.
Antiemetics have been developed to help control the nausea and vomiting associated with chemotherapy, many of which can be extremely effective:
- Serotonin-receptor antagonists, such as ondansetron and granisetron, to reduce nerve activity
- Neurokinin-1 antagonists, such as aprepitant or metoclopramide, to reduce nerve activity
- Steroids, such as dexamethasone or prednisone, to suppress immune response
- Benzodiazepines, such as lorazepam, which have sedative effects
Talk with your doctor to see if one or a combination of these antiemetic medications is right for you.
Chemotherapeutic drugs can cause painful side effects as well. They can damage nerves, most often in the fingers and toes, which leads to burning, numbness, tingling, or shooting pain. Some drugs also cause mouth sores, head and muscle aches, and joint pain and stomach pain. Because not everyone who undergoes chemotherapy experiences pain, it is important to let your doctor know if you feel pain. Steps can be taken to relieve it. There are many different medications and methods to help control pain.
Pain is often measured on a scale from 0-10 (with 0 as no pain). Keep a journal to know the timing, location, and type of pain. Write down any steps taken and if it made the pain better or worse.
The goal of pain control is to prevent pain that can be prevented and to control pain that cannot be prevented. Talk with your doctor to determine what method or methods will work best for you.
Hair loss is a notorious side effect of chemotherapy, but not all chemotherapeutic drugs cause hair loss. Talk with your doctor to see if the regimen you are on may cause hair loss.
Hair loss usually occurs between 10 and 21 days after drug administration. It may happen suddenly and in large amounts or hair may fall out gradually. Hair loss is temporary and hair should grow back after treatment is stopped.
To care for the scalp and hair:
- Use a mild shampoo.
- Use a soft hair brush.
- Use low heat when drying your hair.
- Have your hair cut short—a shorter style will make your hair look fuller and thicker.
- Use a sunscreen, sunscreen, hat, or scarf to protect your scalp from the sun.
- Avoid perming, dying, or relaxing your hair.
- Keep your head covered in the winter to prevent heat loss.
Although not life-threatening, hair loss can be very upsetting. Many people buy a wig or hairpiece, or use hats or scarves, to cover their head. If you buy a wig because of cancer treatment, it is a tax-deductible expense and may be covered in part by health insurance. Shop for these items before any hair falls out to get the best match.
Bone Marrow Suppression
One of the most common side effects of chemotherapy is bone marrow suppression, also known as myelosuppression. Bone marrow is the tissue inside of some bones, such as the sternum (breastbone), hip, femur (thigh), and humerus (upper arm), which produces white blood cells, red blood cells, and platelets. Because cells in the bone marrow tissue grow and divide rapidly, they are susceptible to the effects of chemotherapy.
Blood cell counts do not drop immediately after starting chemotherapy because the drugs do not kill cells already in the blood stream. Chemotherapeutic drugs, instead, prevent bone marrow from forming new blood cells. Each type of blood cell has an average life span, which has an impact on when each type of blood cell reaches its lowest levels, called the nadir. The average life spans are:
- White blood cells—6 hours
- Red blood cells—120 days
- Platelets—10 days
Low White Blood Cell (WBC) Counts
Blood normally has between 4,000 and 10,000 WBCs per cubic millimeter. When your white blood cell count falls, it is known as neutropenia
. The main function of white blood cells is to help the body resist infection. Because the white blood cells play such an important role in your health, your doctor will monitor your white blood cell level carefully.
If your WBC count falls, you will not automatically get an infection. But, it is important to watch for signs and symptoms of a possible infection:
- Shaking chills
- Sore throat
- Shortness of breath
- A new cough
- Nasal congestion
- Burning sensation during urination
- Redness, swelling, and warmth at site of an injury
Naturally occurring hematopoietic growth factors stimulate the production of different types of blood cells. These growth factors can be produced in a laboratory and are available as drugs. The 2 growth factors that stimulate production of white blood cells are granulocyte-macrophage colony stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF). They are frequently given the day after you start chemotherapy and for up to 2 weeks.
There are things you can do to decrease your risk of infection:
Wash your hands often
during the day—Always before you eat, after going to the bathroom, and after touching animals.
Stay away from people who have illnesses that you can catch, like a
- Try to avoid crowds.
Stay away from children who have recently received "live virus" vaccines, like chickenpox or oral
- Maintain proper oral health.
- Do not eat raw fish, seafood, meat, or eggs.
- Clean cuts and scrapes right away and daily until healed.
Report any signs of infection to your doctor immediately.
Low Red Blood Cell (RBC) Counts
A low level of red blood cells is called anemia. Blood normally has between 4 and 6 million red blood cells per cubic millimeter. Red blood cells carry oxygen to all parts of your body. If your red blood cell count drops, you may experience the following:
- Lightheadedness or fainting
- Shortness of breath
- Heart palpitations or a sensation of irregular heartbeats
- Chest pain
- Nausea and vomiting
If you are anemic, the following suggestions may help you feel less tired:
- Get plenty of rest. Sleep more at night and take naps during the day.
- Limit your activities.
- Ask for help when you need it.
- Eat a well-balanced diet.
- When sitting, get up slowly. When lying down, sit first and then stand.
Erythropoietin is a naturally occurring growth factor that stimulates red blood cell production. The drug forms are called erythropoiesis-stimulating agents (ESAs). ESAs are usually given 3 times per week by injection under the skin, until red blood cell counts rises.
Low Platelet Counts
A low platelet count is called thrombocytopenia. The normal range for platelet counts is between 150,000 and 450,000 per cubic millimeter. Platelets are the blood cells that help stop bleeding by making your blood clot. Signs that your platelet count is low include the following:
- Easy bruising
- Heavy or longer menstrual periods
- Bleeding longer than usual after minor cuts or scrapes
- Bleeding gums or nose bleeds
- Developing large bruises (ecchymoses) and multiple small bruises (petechiae)
Very low platelet counts can lead to serious internal bleeding. If your platelet counts fall below a specific number, you may be given platelet transfusions. Oprelvekin, a platelet growth factor, can be given if you have severe thrombocytopenia.
Lack of Appetite
Many chemotherapy drugs cause a decrease in or complete loss of appetite. Each person is different and there is no way to predict how chemotherapy will affect you. But, appetite loss and weight loss can range from mild to severe and may lead to malnutrition. The decrease in appetite is usually temporary. Your appetite should return after chemotherapy has stopped, but it may take several weeks.
In those with certain types or advanced cancers that are resistant to treatment, cachexia is possible. Cachexia, or wasting, is a significant loss of weight and muscle mass, which can occur without loss of appetite or decreased intake of calories. Treating the cancer is the most effective way to overcome cachexia. Dietary changes or medications have little effect on regaining lost weight.
Because chemotherapy can alter your sensation of taste, the therapy can affect the way some foods taste and smell to you, adding to your poor appetite and weight loss. Your taste and smell should return to normal several weeks after chemotherapy has ended.
In order for your body to fight the cancer and cope with chemotherapy, it is important that you get proper nutrition. If you are experiencing loss of appetite, talk with your doctor—there are medications that can help.
There are some things you can do to boost nutrition:
- Eat several small meals throughout the day, instead of a few larger meals.
- Avoid drinking fluids with meals to prevent from feeling full.
- Eat foods high in protein, such as eggs, peanut butter, nuts, dairy products, tuna, and beans.
- Make eating more pleasurable; eat with friends in a relaxing environment.
- Breakfast may be the most tolerable meal of the day; try to include at least one-third of your calories in this meal.
- Monitor and record your weight weekly.
Central Nervous Systems Problems
Some chemotherapy drugs can affect your central nervous system. These side effects can occur soon after chemotherapy or years later:
- Stiff neck
- Nausea and vomiting
- Lethargy or sleepiness
Mouth, Gum, and Throat Problems
Some chemotherapeutic drugs can cause sores and inflammation in the mouth, known as stomatitis. Changes in the throat (pharyngitis) or esophagus (esophagitis) can also occur. Mucositis is the term used to refer to inflammation of the lining of the mouth, throat, and esophagus.
There are some things you can do to help keep your mouth, gums, and throat healthy:
- If possible, see your dentist several weeks before you start chemotherapy. You may need to have your teeth cleaned and to take care of any problems such as cavities, gum abscesses, gum disease, or poorly fitting dentures. Talk with your doctor before undergoing any dental procedure.
- Ask your dentist to show you the best ways to brush and floss your teeth during chemotherapy.
- Brush your teeth and gums after every meal. Use a soft toothbrush and a gentle touch; brushing too hard can damage soft mouth tissues.
- Rinse with warm salt water after meals and before bedtime.
- Rinse your toothbrush well after each use and store it in a dry place.
- Avoid mouthwashes that contain any amount of alcohol.
- If you develop sores in your mouth, talk to your doctor. Medications may soothe discomfort.
If you do experience mouth sores, try the following to help manage them:
- Eat foods cold or at room temperature. Hot or warm foods can irritate a tender mouth and throat.
- Eat soft, soothing foods, such as ice cream, milkshakes, baby food, soft fruits (bananas and applesauce), mashed potatoes, cooked cereals, soft-boiled or scrambled eggs, yogurt, cottage cheese, macaroni and cheese, and puddings.
- Puree cooked foods in the blender to make them smoother and easier to eat.
- Avoid irritating, acidic foods and juices, such as tomato and citrus juice, spicy or salty foods, and rough or coarse foods such as raw vegetables, granola, popcorn, and toast.
Reproduction and Sexual Problems
Chemotherapy can cause reproductive and sexual problems. Whether or not you experience these changes will depend on a few factors:
- Your age when treated
- Dose and duration of the chemotherapy
- Which chemotherapy drugs are given
Everyone responds to treatment differently. Side effects may or may not affect you. Don't feel embarrassed to talk with your doctor about your concerns regarding sexual and reproductive side effects.
Some reproductive and sexual changes a woman may experience include the following:
- Temporary or permanent damage to the ovaries
- Disruption or stoppage of the menstrual cycle
Symptoms of early
menopause, such as hot flashes, vaginal dryness, and tightness during intercourse
- Irritation and dryness of the lining of the vagina
- Vaginal infections
Men undergoing chemotherapy should use condoms because of the changes in or damage to sperm cells, which can create pregnancy or birth complications.
Other reproductive and sexual changes a man may experience include the following:
- Decrease in sexual desire
- Difficulty getting and maintaining an erection
Some side effects can lead to infertility
in both men and women. If you and your partner are planning a family, talk to the doctor before you start treatment. There are resources and treatments available to preserve fertility while undergoing chemotherapy so you can have your family after. Some options may also be available for children or adolescents depending on their stage of development.