National Cancer Institute:

https://training.seer.cancer.gov/treatment/chemotherapy/

Chemotherapy as a cancer treatment can be traced back to the ancient Egyptians, who used compounds of barley, pigs’ ears, and other ingredients to treat cancers of the stomach and the uterus.

During World War II, it was found that soldiers who were exposed to sulfur mustard suffered from lower white blood cell counts. This discovery led to the use of nitrogen mustard, a similar but less toxic chemical agent, to cure patients with high white blood cells counts (lymphoid leukemia) and lymphomas. Later, more chemical substances were studied and tested, becoming chemotherapeutical drugs for cancer treatment.

Chemotherapy is a distinctively different approach than surgery and radiation therapy to treat cancer. Rather than physically removing a tumor or a part of it, chemotherapy uses chemical agents (anti-cancer or cytotoxic drugs) to interact with cancer cells to eradicate or control the growth of cancer.

Cells divide by going through a cell cycle, following an ordered set of events that include the synthesis of DNA (S-phase), mitosis (M-phase), culminating in cell growth and division into two daughter cells. Normal cells grow and die in a precisely controlled way while cancer occurs when the process becomes abnormal, with cells dividing and forming more cells without control and order.

In chemotherapy, drugs that interfere primarily with DNA synthesis and mitosis (the S and M phases of the cell cycle) are used to destroy cancer cells. Different agents work through many different mechanisms: some damage a cell’s genetic material (DNA); some prevent the cell from dividing.

Since chemotherapeutic drugs cannot distinguish between normal cells and cancer cells, both types of cells are affected by chemotherapy. Toxicity of chemotherapeutic agents to normal cells is the cause of unpleasant side effects. However, the value of chemotherapy lies in the fact that the killing effect of chemotherapeutic agents has a definite selectivity for cancer cells over normal host cells. Normal tissues are able to repair themselves and continue to grow, so the injury caused by chemotherapy is rarely permanent.

Chemotherapy

Chemotherapy is a systemic method of cancer treatment, in contrast with local therapies such as surgery and radiation therapy. The drugs used in chemotherapy are able to reach most parts of the body. Therefore, chemotherapy is likely to be recommended for cancer that has already spread to other areas of the body, for tumors that occur at more than one site, or for tumors that cannot be removed surgically. It is also used when a patient has recurrent disease after initial treatment with surgery or radiation therapy.

Chemotherapy is less mutilating than surgery and helps conserve organ or limb function since anti-cancer drugs are used to act on cancer cells without direct removal of a body part.

For some cancers, chemotherapy alone can destroy all the cancer cells and cure the cancer (primary treatment). As an adjuvant treatment, chemotherapy is given prior to, or after other methods, to increase the effectiveness of cancer treatment. Most often, adjuvant chemotherapy is given after other therapies have destroyed the clinically detectable cancer cells. The purpose of adjuvant chemotherapy is to reduce the risk of recurrence or to prolong survival. If cure is not possible, chemotherapy may be given to minimize the discomfort caused by cancer or slow the progression of the disease to prolong the patient’s life (palliative treatment).

As a primary treatment, chemotherapy is used for some cancers such as Hodgkin’s disease, leukemia, Burkitt’s lymphoma, localized diffuse large cell lymphoma, Wilms’ tumor, small cell lung cancer, and testicular cancer.

Chemotherapy may be given prior to surgical resection or radiation therapy to shrink the tumor and make it easier to resect. This type of chemotherapy is called neo-adjuvant, induction, or preoperative chemotherapy.

As a palliative therapy, chemotherapy can be used to help make the cancer patient’s life as comfortable as possible. In the case of Waldenstrom’s macroglobulinemia, which is generally considered incurable, chemotherapy is administered to relieve symptoms and serious complications such as anemia.

Every cancer is unique, as is every cancer patient; therefore, the oncologist takes great care to tailor the chemotherapy plan to the particular case. The treatment protocol specifies what type of drug(s) should be given, what dosage should be given, how to administer the drug(s), how often the drug(s) should be given, and how long the treatment should last. During chemotherapy, the oncologist, who may change or modify the treatment plan to achieve better results, closely monitors the progress of the cancer patient and the tumor response.

Types of Chemotherapy Drugs

Just like scalpels, lasers, and electric currents are used in surgery, the weapons used to fight cancer in chemotherapy are a host of anti-cancer drugs. How differently these drugs kill cancer cells, or prevent them from dividing, depends on their classification. Drugs in the same class kill cancer cells by the same mechanism: they all attack the same target within the cell.

Depending on the type of cancer and the kind of drug used, chemotherapy drugs may be administered differently. They can be administered orally (oral chemotherapy), or injected into a muscle (intramuscular injection), injected under the skin (subcutaneous injection), or into a vein (intravenous chemotherapy). In special cases, chemotherapy drugs may be injected into the fluid around the spine (intrathecal chemotherapy). Two or more methods of administration may be used at the same time under certain circumstances. No matter what method is used, chemotherapy drugs are absorbed into the blood and carried around the body.

Of all the methods of chemotherapy drug administration mentioned above, intravenous injection is most commonly used. It is the most efficient way to get the medication into the bloodstream. Oral chemotherapy is more convenient and does not require any specialized equipment.

In chemotherapy, cancer patients may be given one or several drugs from the available anti-cancer drugs. Since different chemical agents damage cancer cells in different ways and at different phases in the cell cycle, a combination of drugs is often employed to increase the cancerous cell-killing effectiveness. This is called combination chemotherapy.

Listed below are several major categories (classes) of chemotherapy agents based on their chemical structures and the way they act on cancer cells:

Alkylating agents

Alkylating agents were among the first anti-cancer drugs and are the most commonly used agents in chemotherapy today. Alkylating agents act directly on DNA, causing cross-linking of DNA strands, abnormal base pairing, or DNA strand breaks, thus preventing the cell from dividing. Alkylating agents are generally considered to be cell cycle phase nonspecific, meaning that they kill the cell in various and multiple phases of the cell cycle. Although alkylating agents may be used for most types of cancer, they are generally of greatest value in treating slow-growing cancers. Alkylating agents are not as effective on rapidly growing cells. Examples of alkylating agents include chlorambucil, cyclophosphamide, thiotepa, and busulfan.

Antimetabolites

Antimetabolites replace natural substances as building blocks in DNA molecules, thereby altering the function of enzymes required for cell metabolism and protein synthesis. In other words, they mimic nutrients that the cell needs to grow, tricking the cell into consuming them, so it eventually starves to death.

Antimetabolites are cell cycle specific. Antimetabolites are most effective during the S-phase of cell division because they primarily act upon cells undergoing synthesis of new DNA for formation of new cells. The toxicities associated with these drugs are seen in cells that are growing and dividing quickly. Examples of antimetabolites include purine antagonists, pyrimidine antagonists, and folate antagonists.

Plant alkaloids

Plant alkaloids are antitumor agents derived from plants. These drugs act specifically by blocking the ability of a cancer cell to divide and become two cells. Although they act throughout the cell cycle, some are more effective during the S- and M- phases, making these drugs cell cycle specific. Examples of plant alkaloids used in chemotherapy are actinomycin D, doxorubicin, and mitomycin.

Antitumor antibiotic

Antitumor antibiotics are cell cycle nonspecific. They act by binding with DNA and preventing RNA (ribonucleic acid) synthesis, a key step in the creation of proteins, which are necessary for cell survival. They are not the same as antibiotics used to treat bacterial infections. Rather, these drugs cause the strands of genetic material that make up DNA to uncoil, thereby preventing the cell from reproducing. Doxorubicin, mitoxantrone, and bleomycin are some examples of antitumor antibiotics.

One of the most important decisions for the oncologist is prescribing the right amount of anti-cancer drugs. Although large doses will kill more cells, greater amounts of drugs will produce more severe side effects. However, lowering the dosage to minimize side effects will also reduce the chances of success. The usual practice is to use the maximum safe dose for effectiveness, even at the cost of temporary side effects. The following section will discuss some common side effects caused by anti-cancer drugs and ways to cope with them.