What is Chemotherapy?

Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more chemotherapeutic agents (anti-cancer drugs) to destroy rapidly growing cells in the body, such as cancer cells which grow and divide faster than other cells in the body. Chemotherapy is primarily used to lower the total number of cancerous cells in the body and shrink tumour size. In the case of advanced stage cancers, chemotherapy may help to relieve pain.

History of Chemotherapy

The use of chemotherapy to treat cancer began at the start of the 20th century. Several attempts were made to narrow down the chemicals that might affect the disease by developing various methods to screen chemicals using transplantable tumours in the rodents. Chemotherapy was first coined as a word in the early 1900s by a German chemist Paul Ehrlich, who defined it as the use of chemicals to treat disease[1].

During World War I, mustard gas was used as a chemical warfare agent. It was discovered that the gas was a potent suppressor of haematopoiesis (blood production). Similarly, nitrogen mustards were studied during World War II after the effects of an accidental spill of sulphur mustards on troops from a bombed ship in Bari Harbour, Italy[2]. This incident led to an observation that both bone marrow and lymph nodes were marked depleted in those who were exposed to mustard gas. It was believed that an agent which could damage the rapidly growing white blood cells might have a similar effect on cancer. The first chemotherapeutic drug developed from this research was Mustine (chlormethine, sold under the brand name of Mustargen). Sidney Farber collaborated with Lederle Laboratories to develop a series of folic acid analogues. These compounds included aminopterin and amethopterin, now known as methotrexate. Farber tested these antifolate compounds in children with leukaemia and in 1948, the results of these tests showed unquestionable remissions[3]. Farber is regarded as the father of modern chemotherapy.

In the mid-1950s, Charles Heidelberger and his colleagues developed a drug that was aimed at non-hematologic cancers[4]. Heidelberger “targeted” a biochemical pathway by attaching a fluorine atom to the 5-position of the uracil pyrimidine base which resulted in the synthesis of fluoropyrimidine 5-fluorouracil (5-FU). This agent was found to have broad-spectrum activity against a range of solid tumours and to this day, remains the cornerstone for the treatment of colorectal cancer. This agent represents the very first example of targeted therapy which has now become a focus in current cancer drug development, although the target, in this case, was a biochemical pathway instead of a molecular pathway.

Methods

• Combined modality chemotherapy is the use of drugs along with other cancer treatments like surgery, radiation therapy, ayurvedic treatment (such as Cancertame), homeotherapy treatment etc
• Combination chemotherapy involves treating a person with a number of different drugs simultaneously. This is one of the most used methods in chemotherapy as it minimises the chances of resistance developing to any one agent. For the treatment of bladder cancer, for example, a combination of Methotrexate, vincristine, doxorubicin, cisplatin is used
• Neoadjuvant chemotherapy is given with an aim to shrink the tumour prior to principal treatment such as radiotherapy or surgery[5] 
• Adjuvant chemotherapy is given after principal treatment. It is an effective treatment if the cancerous cells have spread to other parts of the body

Types of Chemotherapy

1) Alkylating agents are the oldest group of chemotherapeutics in use today. There are several types of alkylating agents used in chemotherapy treatments such as:

• Mustard gas derivatives -  Mechlorethamine, Cyclophosphamide, Chlorambucil, Melphalan, and Ifosfamide
• Ethylenimines - Thiotepa and Hexamethylmelamine
• Alkyl sulfonates - Busulfan
• Hydrazines and Triazines - Altretamine, Procarbazine, Dacarbazine and Temozolomide
• Nitrosoureas - Carmustine, Lomustine and Streptozocin.  Nitrosoureas are unique because, unlike most types of chemo treatments, they can cross the blood-brain barrier.  They can be useful in treating brain tumours.
• Metal salts - Carboplatin, Cisplatin, and Oxaliplatin

• Folic acid antagonist - Methotrexate
• Pyrimidine antagonist - 5-Fluorouracil, Floxuridine, Cytarabine, Capecitabine, and Gemcitabine
• Purine antagonist - 6-Mercaptopurine and 6-Thioguanine
• Adenosine deaminase inhibitor - Cladribine, Fludarabine, Nelarabine and Pentostatin

• Topoisomerase I inhibitors - Irinotecan, topotecan
• Topoisomerase II inhibitors - Amsacrine, etoposide, etoposide phosphate, teniposide

• Vinca alkaloids (made from Catharanthus roseus) - Vincristine, Vinblastine and Vinorelbine
• Taxanes (made from Taxus) - Paclitaxel and Docetaxel
• Podophyllotoxins (derived from may apple plant) - Etoposide and Tenisopide
• Camptothecin analogues (derived from camptothecin acuminate) - Irinotecan and Topotecan

Side Effects of Chemotherapy

Chemotherapy can produce adverse side effects that range from mild to severe, depending on the type and extent of the treatment. Some people may experience adverse to a few side effects which vary from person to person and the stage of cancer. Toxicities related to chemotherapy can occur acutely within hours to days, or chronically, after weeks to years[6].

Some common side effects of chemotherapy are:

• Nausea and vomiting
• Hair loss
• Skin changes
• Nail changes
• Fatigue
• Hearing impairment
• Infections
• Bleeding problems
• Anaemia
• Loss of appetite
• Bowel problems
• Cognitive and mental health problems

Luckily, due to advancement in medical research, ayurvedic drugs such as Cancertame when taken along with chemotherapy can minimize such side effects providing for a better integrative treatment for cancer patients.

New Treatment Management Protocols 

The practice of utilizing chemotherapy for the treatment of cancer began in the 1940s and still remains a fundamental treatment for various types of cancer. Given the poisonous origin of chemotherapy, patients receiving these treatments experienced some severe side effects which create a demand for new treatment management protocols. Research over the past 30 years has led to the discovery of medications aimed at reducing the side effects of chemotherapy.

• Targeted therapies became more popular and are one of the major focus of current cancer drug development. Although the very first use of this method was done back in the 1950s, this therapy aims for the specific targets that are specific to cancer cells and do not occur or are rare in healthy cells
• Electrochemotherapy is a combined treatment in which an injection of a chemotherapeutic drug is followed by the application of high-voltage electric pulses to the tumour. This treatment enables the chemotherapeutic drugs, which cannot or hardly go through the membrane of cells, to enter cancer cells
• Hyperthermia therapy is a heat treatment of cancer that can be very effective if combined with chemotherapy. The heat can be applied locally to the tumour site, which will dilate blood vessels to the tumour, allowing the more chemotherapeutic medication to enter the tumour. The tumour cell membrane will become more porous which will further allow more of the chemotherapeutic medicine to enter the tumour cell
• Other medications such as Cancertame can also help to reduce the side effects of chemotherapy by enhancing the immune system of the body, and also helps to fight the growth of cancer by inducing apoptosis (cell death) and inhibiting tumour angiogenesis.

References