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Chemotherapy

Uses

Chemotherapy or anticancer agents are the primary treatment for cancers such as leukemia, lymphoma and breast.

These medications are used to cure cancer, keep cancer from spreading, to slow cancer’s growth and to kill cancer cells that have spread to other part of the body. Chemotherapy may be used alone for some types of cancer or in combination with other treatments such as radiotherapy or surgery.

Mechanism of Action

Chemotherapy are toxic to cancer cells. They all work by interfering with the ability of cancer cells to divide and reproduce themselves

Types of Chemotherapy

Chemotherapy can be divided into several groups based on factors such as how they work, their chemical structure, and their relationship to another drug. Because some drugs act in more than one way, they may belong to more than one group.

1. Alkylating agents

Alkylating agents directly damage DNA to prevent the cancer cell from reproducing. Alkylating agents are used to treat many different cancers, including leukemia, lymphoma, Hodgkin disease, multiple myeloma, and sarcoma, as well as cancers of the lung, breast, and ovary.

There are different classes of alkylating agents, including:

  • Nitrogen mustards: such as mechlorethamine (nitrogen mustard), chlorambucil, cyclophosphamide, ifosfamide, and melphalan
  • Nitrosoureas: which include streptozocin, carmustine and lomustine
  • Alkyl sulfonates: busulfan
  • Triazines: dacarbazine and temozolomide
  • Ethylenimines: thiotepa and altretamine (hexamethylmelamine)

The platinum drugs (cisplatin, carboplatin, and oxalaplatin) are sometimes grouped with alkylating agents because they kill cells in a similar way.

2. Antimetabolites

Antimetabolites are a class of drugs that interfere with DNA and RNA growth by substituting the normal building blocks of RNA and DNA

They are commonly used to treat leukemia’s, cancers of the breast, ovary, and the intestinal tract, as well as other types of cancer.

Examples of antimetabolites include:

  • 5-fluorouracil
  • 6-mercaptopurine
  • Capecitabine
  • Cladribine
  • Clofarabine
  • Cytarabine
  • Fludarabine
  • Gemcitabine
  • Hydroxyurea
  • Methotrexate
  • Pemetrexed
  • Thioguanine

3. Anti-tumor antibiotics

Anthracyclines

Anthracyclines are anti-tumor antibiotics that interfere with enzymes involved in DNA replication. They are widely used for a variety of cancers. Examples of anthracyclines include:

  • Daunorubicin
  • Doxorubicin
  • Epirubicin
  • Idarubicin

Other anti-tumor antibiotics

Anti-tumor antibiotics that are not anthracyclines include:

  • Actinomycin-D
  • Bleomycin
  • Mitomycin-C
  • Mitoxantrone

4. Topoisomerase inhibitors

These drugs interfere with enzymes called topoisomerases, which help separate the strands of DNA so they can be copied. They are used to treat certain leukemias, as well as lung, ovarian, gastrointestinal, and other cancers.

Examples of topoisomerase I inhibitors include topotecan and irinotecan.

Examples of topoisomerase II inhibitors include etoposide and teniposide. Mitoxantrone also inhibits topoisomerase II.

5. Mitotic inhibitors

Mitotic inhibitors are often plant alkaloids and other compounds derived from natural products. They can stop mitosis or inhibit enzymes from making proteins needed for cell reproduction.

They are used to treat many different types of cancer including breast, lung, myelomas, lymphomas, and leukemias. These drugs are known for their potential to cause peripheral nerve damage, which can be a dose-limiting side effect.

Examples of mitotic inhibitors include:

  • Taxanes: paclitaxel and docetaxel
  • Vinca alkaloids: vinblastine, vincristine, and vinorelbine.

6. Miscellaneous chemotherapy drugs

Some chemotherapy drugs act in slightly different ways and do not fit well into any of the other categories.

Examples include drugs like L-asparaginase, which is an enzyme.

7. Hormone therapy

Drugs in this category are sex hormones, or hormone-like drugs, that change the action or production of female or male hormones. These cancer treatment hormones do not work in the same ways as standard chemotherapy drugs, but rather by preventing the cancer cell from using the hormone it needs to grow, or by preventing the body from making the hormones.

Examples include:

  • The anti-estrogens: fulvestrant, tamoxifen, and toremifene
  • Aromatase inhibitors: anastrozole, exemestane, and letrozole
  • Progestins:megestrol acetate
  • Estrogens
  • Anti-androgens: bicalutamide, flutamide, and nilutamde
  • Gonadotropin-releasing hormone (GnRH), also known as luteinizing hormone-releasing hormone (LHRH) agonists or analogs: leuprolide and goserelin.

Route of Administration

The medicines usually need to get into the bloodstream to get to all areas of the body to reach any cancerous cell which may be present.

Intravenous chemotherapy

To get straight into the bloodstream, many chemotherapy are given by injection directly into a vein (intravenous)

Chemotherapy given by mouth

Some chemotherapy medicines can be taken as tablets or liquids by mouth and are absorbed into the bloodstream from the gut.

Other methods

Anticancer agents usually do not get into the brain or spinal cord very well from the bloodstream. So, to treat some cancers of the brain or spinal cord, chemotherapy may be injected into the fluid which surrounds the brain and spinal cord. This is done by a lumbar puncture when a needle is inserted into the space next to the spinal cord in the lower back.

In certain situations chemotherapy may be given by injection into a muscle, injected into the chest cavity, or even injected directly into a cancerous tumour.

Side-effects of chemotherapy

Anticancer agents are powerful and often cause unwanted side-effects. Chemotherapy work by killing cells which are dividing and so some normal cells are damaged too. However, side-effects vary from chemotherapy to chemotherapy. Even with the same chemotherapy, different people can react differently. Some people develop more severe side-effects than others who take the same chemotherapy.

Tiredness

Tiredness (fatigue) is a common side-effect. It is likely that patients will feel more tired than normal during a course of chemotherapy. Patients may need to cut back on your normal activities, plan regular rests and, if possible, take some regular light exercise. Some people feel overwhelmingly tired and may need to rely on other people to do routine daily chores.

Nausea and vomiting

It can be common to feel sick (nausea) during and after each cycle of treatment. Try to drink plenty of fluids even if you do not feel like it, to prevent dehydration. Sucking ice cubes is one tip to increase fluid intake.

Effects on the blood and immune system

Chemotherapy can affect the bone marrow. The bone marrow is where make red blood cells, white blood cells and platelets are made. Problems which may occur include:

  • Anaemia – This means a low level of red blood cells. If develop anaemia, patients will feel tired and look pale.
  • Serious infection – Patients are more prone to infection if the level of white blood cells goes down too low. This is because he or she has less ability to fight off bacteria, viruses and other germs.
  • Bleeding problems – Platelets help the blood to clot when cuts occur. If the number of platelets in blood goes down patients may bruise easily and bleed for longer than usual after cuts.

Mouth problems

The cells which line the mouth are affected by some chemotherapy. This may lead to a sore mouth, dry mouth or mouth ulcer (mucositis). Routine good mouth care will help to prevent mouth problems from developing or from becoming more serious.

Hair loss

Some chemotherapy medicines damage the hair-making cells. Some or all of hair may fall out. This usually occurs 2-3 weeks after a course of treatment starts. Body hair and eyelashes may also fall out in addition to scalp hair. After the course of treatment has finished, the hair will usually regrow within 4-12 months.

Constipation

This may be helped by eating plenty of foods high in fiber and having lots to drink. A laxative may be needed in some cases.

Diarrhoea

This is a side-effect from some chemotherapy. Patient adviced to increase the amount of drink if develop diarrhoea. If it persists or becomes severe, patients should tell a doctor.

Anti-diarrhoeal medicines may be needed and patient may even need to be admitted to hospital for a drip of fluid if patents become dehydrated due to severe diarrhoea.

Nerve problems

Some chemotherapy can affect nerves. This may lead to a lack of sensation in parts of the body such as the fingers or toes, pins and needles or weakness of muscles. Tell a doctor if any of these symptoms occur.

Fertility

Some anticancer agents can affect fertility in both men and women. It can be temporary or permanent. Some women develop an early menopause when taking some cytotoxic medicines.

Before starting anticancer agents

Depending on the medicines used, patients may have a number of baseline blood tests such as full blood count, liver profile and renal profile to make sure patient is fit for chemotherapy. Some chemotherapy drugs can affect organs such as the heart, lung or the kidneys. You may need tests to measure how well these organs are working before you have chemotherapy. These tests may be repeated during treatment, to check that these organs continue to work well.

Pregnancy and contraception

Although some anticancer agents can reduce fertility, pregnancy is still possible if you are sexually active. However, anticancer agents can damage sperm, ova and an unborn baby. Therefore, it is not advisable to become pregnant if you are a female who is having chemotherapy, or a female partner of a male who is having chemotherapy. If patients are sexually active, they should use reliable contraception.

PBefore starting chemotherapy

Depending on the medicines used, patients may have a number of baseline blood tests such as full blood count, liver profile and renal profile to make sure patient is fit for chemotherapy. Some chemotherapy can affect these organs. These tests may be repeated during treatment, to check that these organs continue to work well.

Reference

  1. Children with Cancer; A Parent’s Guide- National Cancer Society Malaysia
  2. Standford Cancer Center: Understanding Cancer & Treatment.
  3. Handbook of Cancer Chemotherapy. 5th Edition. Lippincott William & Wilkins.
Last reviewed : 25 April 2014
Writer : Rizal Husaini bin Razali
Accreditor : Kamarun Neasa Begam bt. Mohd Kassim