Know About Chemotherapy

What is chemotherapy?

When we hear the word chemotherapy, it is instantly associated with hair loss, cancer and misery. To make the most of chemo, a thorough understanding of what it is and how it works is necessary.

Normal cells follow the life cycle of birth, maturation, function and death. In cancer cells, to put it in simple terms, they do not follow any specific cycle. They do not perform proper function but more importantly, they do not die.

Natural cell death is called apoptosis. It is very important as it maintains the number of cells that are limited at a certain region and allows new cells to be born in its place.

But, in case of cancer cells, apoptosis is absent, which leads to invasion of cells into local structures and also, far off structure. This obstructs the normal functioning of cells.

Chemotherapy is a chemical treatment which involves destruction of cancer calls. But, along with cancer cells, normal healthy cells get destroyed as well. This is what causes the side effects.

How does chemotherapy work?

Chemotherapeutic drugs work on multiple principles:

• Impair mitosis: mitosis is a type of cell division that occurs in normal cells. A single cell splits into two with two separate pairs of DNA’s and genetic material. Chemo drugs can affect dividing cells at the stage of splitting or DNA synthesis. The impaired cells are destroyed and formation of cancer cell is stopped. But along with these normal, rapidly dividing cells, like the blood cells are also affected.
• Nutrition deprivation: chemo drugs can deprive the cancer cells of their nutritional source, which are through blood vessels, enzymes and hormones.
• Trigger apoptosis: apoptosis is the programmed cell death that is required for removing old cells and making space for healthy new cells. This can be triggered by some chemicals which are released by the chemo drugs.

Tests performed before chemotherapy:

Before chemotherapy, the physician evaluates if the patient is fit enough to handle the side effects of the therapy.

• Liver function tests: liver undergoes a lot of stress whenever a new chemical is added to the body as it metabolizes the drug. If the liver is already in a weak condition, chemotherapy is not advised.
• Complete blood picture: if the total number of red blood cells, white blood cells and platelets are already low, chemotherapy will only make it lower.

Blood tests are continued during the treatment as well to know any adverse conditions.

How are chemotherapeutic drugs administered?

Routes of administration of chemotherapeutic drugs vary greatly on the patient’s cooperation, type of cancer, location of cancer, physical health status, age, capacity to withstand the selected route.

Some of the most common routes of administration are:

1. Oral route: if the patient is fit enough, the drug can be taken as a tablet, pills, capsules or liquid form. This can be administered from home, but the patient will require regular check-ups to ensure its proper functioning. Some capsules with protective coating helps in slow release of the drug. This allows to maintain a longer duration between the doses.
2. Sub lingual tablets: are those which can be placed under the tongue for absorption. This allows rapid absorption through the blood stream and has a quick effect. It is especially useful for anti-nausea medications.

Not all medications can be given this way. This is because sometimes the drug gets destroyed by the stomach acids and turn out to be ineffective. The released drug may also not be absorbable by the stomach and intestinal lining which ends up excreted without being metabolized. Sometimes, the drug may damage the intestinal walls if released in the stomach. Few other forms are as follows-

• Subcutaneous injections: the drugs that are injected between the skin and muscle layer are called subcutaneous injections. They do not go to the level of muscles. They are mostly used as chemotherapy support drugs. They are less likely to bleed when compared to intramuscular injections and hence are used in patients who have platelet deficiency.
• Intramuscular injections: the drug is injected into the muscle past the skin. This method causes bleeding within the muscle. Most chemo drugs cannot be administered in this manner as they may cause damage to the tissue wall.
• Intravenous injections: the chemo drugs are directly infused into the patient’s veins and is carried to the blood stream. It is the quickest source of administration with modifiable dosage time and duration. Various methods of intravenous injections are given:
• Angio-catheter: a temporary catheter until drug is administered.
• PICC lines: these are long plastic catheters that may be placed for a longer duration. It could be used for in-patient treatment or at-home infusions. Fluoroscopy X-rays are done to confirm if the catheter is placed in the right position.
• Tunneled catheters: these are catheters placed sub-cutaneous, at the chest, and inserted into the superior vena cava. They have multiple lumen or entry points. They can be left in the patient’s body for months to years with low risk of infection. Regular changing of dressings is necessary. It is used in extensive therapies like bone marrow transplants.
•  Non-tunneled catheters: these are directly entered into the jugular or subclavian vein to reach the superior vena cava. They are done for emergency or short-term treatments. Infections can spread faster and regular dressings are needed.
• Port-a-cath: this is a more permanent device. It can be left unchanged for 3-5 years. It is inserted directly to the superior vena cava in the right atrium of the heart.
• Intraventricular or intrathecal methods: this is when the medication is to be injected into the cerebro-spinal fluid. There are two methods, lumbar tap and ommaya reservoir.
• Intraperitoneal methods: the drug is directly injected into the abdominal cavity and does not go through the stomach or intestines. This is said to reduce the body’s overall exposure to the drug.
• Intra-arterial methods: in this method, the drug is directly infused to the artery that is feeding the tumour.
• Intravesicular chemotherapy: the chemo drugs are infused to the urinary bladder through a catheter.
• Intrapleural chemotherapy:  the chemo drug is injected into the lung cavity or the pleura. It is primarily used in treatment of lung cancers.
• Implantable chemotherapy treatments: implantable structures are placed into the cavity after surgery for slow release of the drug.
• Topical chemotherapy treatments: the chemotherapy drugs can sometimes be applied on the skin like a cream. It is used in cases of skin cancers.

What are the side effects of chemotherapy?

Chemotherapy destroys not only the cancer cells but also the normal, healthy viable cells.

Some of the common side effects are:

1. Hair loss: this is one of the first things noticed by the patient. Hair loss is not only on the scalp, it is throughout the body. Hair loss is a temporary side effect. Hair grows back normally once the treatment is completed. It can be reduced by wearing a cold cap (except in cases of leukaemia). This does not cause any physical health issues but has an adverse effect on the psychology of the patient.

Nails ca become brittle and flaky as well.

• Nausea and vomiting: almost 65 to 70 %of patients face this problem. Anti-emetics (drugs which prevent vomiting) help to reduce and prevent its re-occurrence when the chemotherapy is completed.
•  Low white blood cell count: due to chemotherapy drugs, the number of white blood cells are depleted. This condition is called neutropenia. This makes the patient more susceptible to infections. The patient must take utmost care to protect himself from infections by maintaining proper hygiene and cleanliness.
• Low platelet count: this condition is known as thrombocytopenia. It is a condition in which the patient has reduced platelets due to destruction by the chemotherapeutic agents. This leads to easy bleeding and bruising. This is especially seen when the patient has bleeding gums and small cuts even by razors. Patient needs to take care to not cause any open wounds that might bleed.
• Low red blood cell count: this is known as anaemia.  Red blood cells carry oxygen to the body. They are rapidly destroyed in the presence of chemo drugs. This reduces the overall oxygen supply to the body and makes the patient dizzy, tired and breathless. Patient is usually advised to take foods rich in iron along with iron supplements and erythropoietin.
• Mucositis: this is the inflammation of mucous membranes. It could affect the mucous membrane of any part of the body. It usually manifests orally as a burning sensation with blisters, redness, and ulcerations. Drugs may be prescribed for the reduction of inflammation.
• Appetite loss: chemotherapy and cancer itself can reduce one’s appetite and metabolism. Patients are asked to eat smaller frequent meals and drink fluids through a straw. Patients who are incapable to physically feed on their own are fed through nasogastric tube to maintain nutrition supply.
• Effect on pregnancy and fertility: patient temporarily loses libido. Many chemotherapy drugs cause deformities in the foetus. Patients are advised to avoid pregnancy during chemotherapy. It can also reduce the fertility in both men and women. 
• Cognitive and mental health problems: patients have previously reported short term memory, reduced attention span, reduced capacity to multitask, depression and mood swings.

What are the types of chemotherapeutic drugs available?

The drugs used for chemo are derived from many natural and synthetic sources. There are four main groups:

1. ALKYLATING AGENTS: these are drugs which have a direct impact on the DNA synthesis and disrupts cell cycle at various stages. Ex: chlorambucil, busulfan.
2. ANTIMETABOLITES: these are chemical substances that have structures similar to that of proteins required for the survival of cancer cells. When the cancer cells absorb them, they do not receive any nutritional value and are made to starve. Ex: purine and pyrimidine antagonist.
3. PLANT ALKALOIDS: substances that block the ability of cells to grow and multiply. Ex: actinomycin, mitomycin.
4. ANTITUMOUR ANTIBIOTICS: these are substances which bind to the DNA and stops synthesis of RNA which further deactivates the reproductive capacity of cells. This will reduce the size of tumours and prevent further growth of tumours. Ex: doxorubicin.

 CHEMOTHERAPY FOR SOME COMMON CANCERS:

1- BREAST CANCER

When is chemotherapy given for breast cancer?

 It can be given either before or after surgery.

• Before surgery: chemotherapy is given to reduce the size of the tumour before surgery to have a conservative surgery instead of a complete mastectomy.

It can also be given to patients who have triple negative breast cancer which will not respond to hormone therapy.

• Post – surgery: chemotherapy can be given after surgical excision to prevent reoccurrence of cancer and to destroy the remnant cancer cells which may be left behind after surgery.
• Secondary breast cancer: chemotherapy can be given before surgery of cancer which has attacked for the second time and may have spread to other parts.

Commonly used drugs for chemotherapy of the breast:

• Anthracyclines, such as doxorubicin (Adriamycin) and epirubicin (Ellence)
• Taxanes, such as paclitaxel (Taxol) and docetaxel (Taxotere)
• 5-fluorouracil (5-FU)
• Cyclophosphamide (Cytoxan)
• Carboplatin (Paraplatin)

How is the chemotherapy given?

Chemotherapy is given in the form of:

• Intravenous injections
• Central venous catheters
• Central venous access devices

Other symptoms in breast cancer chemotherapy:

• Menstrual changes: the patient, if of a younger age group may have changes in the menstrual cycle and may even reach menopause at an early age. This may be permanent. It could also lead to loss of fertility.
• Heart damage: when chemo drugs like doxorubicin is used for prolonged duration or at high doses, it could lead to damage to heart tissue damage. Drugs which are to target HER2 are also to be taken with caution.
• Nerve damage: drugs like vinorelbine, eribulin, and taxanes are known to affect the neural system outside the spinal cord and brain (peripheral nervous system). This can lead to numbness, tingling sensation, burning, or sensitivity to heat and cold. This usually vanishes once the treatment is stopped.
• Hand-foot syndrome: drugs like capecitabine and liposomal doxorubicine cause burning, numbness, redness and tingling of skin. It could progress to blistering or swelling which may turn extremely uncomfortable or even painful. Only steroidal creams can be used for symptomatic treatment.
• Risk of leukaemia: very rarely, chemo drugs may cause bone marrow diseases which might lead to myodysplastic syndrome or even acute myeloid leukaemia. But the benefit from chemotherapy is much higher than the risk of leukaemia.

• LUNG CANCER:

When is chemotherapy given for lung cancer?

Chemotherapy for lung cancer is given either on it’s own or as an adjuvant. This means that chemo drugs are given along with other modes of treatments like radiation therapy. Surgery is not always recommended especially in extensive cases as it is difficult to excise the tumour without causing significant damage to vital cells.

• Neo-adjuvant chemotherapy: this is when chemotherapy is given prior to radiation therapy or surgery. It is done to reduce the size of the tumour.
• Post-surgery chemotherapy: it is done to destroy the remnant cancer cells which may cause remission if left out and could not be excised through surgery.
•  Chemotherapy with radiation therapy: in cases of stage III lung cancer where surgery is not possible, the doctor may recommend chemotherapy with high dose radiation therapy.
• Chemotherapy alone: in stage IV lung cancer, chemotherapy is the main mode of treatment. It is also given for palliative therapy in cases of advanced cases.

Chemotherapy is mainly prescribed in non-small cell lung cancers. The drugs used are:

• Cisplatin
• Carboplatin
• Paclitaxel
• Albumin-bound paclitaxel
• Docetaxel
• Gemcitabine
• Vinorelbine
• Irinotecan
• Etoposide
• Vinblastine
• Pemetrexed

Most of the times, a combination of two or three drugs are used.

Some of the common side effects are hair loss, fatigue, mouth sores, loss of appetite, nausea, vomiting, diarrhoea or constipation, increased risk of infections and easy bruising and bleeding.

2- BONE CANCER

In case of bone cancers, chemotherapy is not very useful. They do not usually respond to chemotherapeutic drugs. Nevertheless, chemotherapy is used as an adjuvant for osteosarcomas and Ewing sarcoma.

 Common drugs used in treatment of bone cancers:

• Doxorubicin
• Cisplatin
• Etoposide
• Ifosfamide
• Cyclophosphamide
• Methotrexate
• Vincristine

The doctor may prescribe a combination of two or three drugs for the treatment.

Specific side effects:

• Cisplatin: this drug may cause peripheral neuropathy. This leads to numbness, tingling sensations, pain and burning sensations. It may cause ototoxicity which results in deafness.
• Ifosfamide and cyclophosphamide: these drugs may damage the urinary bladder lining and cause bloody urine. This is called haemorrhagic cystitis.
• Doxorubicin: this drug is known to cause damage to the heart.
• OVARIAN CANCER:

Chemotherapy for ovarian cancer is mostly an adjuvant therapy with surgery or radiation therapy. It is given as intravenous or intraperitoneal route.

Epithelial ovarian cancer in its initial stage is treated with chemotherapy only.

Some of the chemo drugs used in ovarian cancer treatment are:

• Albumin bound paclitaxel
• Altretamine
• Capecitabine
• Cyclophosphamide
• Etoposide
• Gemcitabine
• Ifosfamide
• Irinotecan
• Liposomal doxorubicin
• Melphalan
• Pemetrexed
• Topotecan

Some of the common side effects of these drugs are hair loss, weight loss, fatigue, hand-foot syndrome, nausea, vomiting, mouth sores.

3- PROSTATE CANCER

When is chemotherapy used in prostate cancer?

Chemotherapy is usually used when:

• Hormone therapy does not have effective results.
• Adjuvant to hormone therapy
• Adjuvant to surgical or radiotherapy

Chemotherapeutic drugs used for prostate cancers:

• Docetaxel
• Cabazitaxel
• Mitoxantrone
• Estramustine

Specific side effects of chemo drugs for prostate cancer:

• Docetaxel and cabazitaxel: these drugs are known to have adverse allergic reactions and peripheral neuropathy.
• Mitroxatrone: this drug, in high doses and rare conditions, is said to cause leukaemia.
• Estramustine: this drug carries an increased risk of clot formation.

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