One of the 3 modalities of cancer, chemotherapy is a line of treatment that uses drugs to destroy cancer cells. The term literally means ‘treatment of diseases by chemicals’ and is derived from the German word chemotherapie with the prefix chemo meaning chemicals and therapie meaning healing or treatment. Chemotherapy drugs are strong chemicals that target cancer cells at particular stages of the cell cycle. The cell cycle is a process that all cells undergo to create new healthy cells.
Chemotherapy uses drugs that are cytotoxic signifying that they not only kill the malignant cancer cells but also impact the healthy cells of the body. Chemotherapy drugs are either regional, which means they target a particular area of the body, or systemic, which means they enter the bloodstream and reach the cancer that has metastasised.
The treatment’s main goal is to obstruct the cell reproduction process that takes place at various stages of the cell cycle. It is used to reduce the size of a tumor before receiving additional treatments like radiation therapy or surgery. It is also employed to eliminate any remaining cancer cells following other treatments. Combination chemotherapy began to take on importance once micrometastases and cancer recurrence following surgery and radiation therapy were discovered.
Chemotherapy has a greater impact on cancer cells because they undergo this process more quickly than healthy cells. Chemotherapy can harm healthy cells as well during their regular cell cycle because it permeates the entire body. This is why chemotherapy can cause severe side effects such as hair loss, nausea and bleeding and bruising.
Different Chemotherapy Terms
- Curative chemotherapy – Curative treatment means that the aim of chemotherapy is to completely eradicate any measurable trace of the disease. Chemotherapy, when used as a stand alone form of treatment, is able to achieve this only in a few cancer types such as some leukemias, lymphomas and some germ cell tumors. When referring to the use of curative chemotherapy in cases of Hodgkin’s lymphoma, testicular cancer, and acute lymphocytic leukemia, chemotherapy may show positive results. This description also includes the use of chemotherapy as adjuvant treatment after surgery for lung, colorectal, or localized breast cancer.
- Neoadjuvant chemotherapy – Neoadjuvant therapy has four main rationales. Firstly, it should render an otherwise inoperable tumors operable or, secondly, allow more conservative surgery. Thirdly, starting systemic treatment preoperatively was hoped to lead to improved overall survival in patients with locally advanced cancers, who are at high risk of having distant disease. Finally, unlike adjuvant chemotherapy given in the absence of any measurable disease, neoadjuvant chemotherapy gives us the opportunity to observe the tumor shrink both palpably and on imaging, enabling a rapid assessment of clinical response. This could help test responses in vivo to new drug regimens, which could then be used as adjuvant therapies.
- Adjuvant chemotherapy – Treatment used following primary therapy to eradicate any residual cancer cells and lower the risk of cancer recurrence is referred to as adjuvant chemotherapy. If a tumor is removed after surgery, there is always a good chance that a small number of cancer cells may have spread into the lymphatic system or the bloodstream. However, the number of these cells may be so small that they may be undetectable. These are referred to as micrometastasis and administering chemotherapy after surgery will reduce the chances of these cells forming recurrent tumors or metastases in the future.
- Combination Chemotherapy – In many cases, chemotherapy is used concurrently, which means in combination with other lines of treatment such as radiation. This is usually done to make cells more sensitive to radiation and thereby increase the success rate of both radiation therapy and chemotherapy.
How is Chemotherapy Administered ?
Chemotherapy is generally administered orally or through intravenous methods . This can be done with the help of a peripheral intravenous cannula.
This method is preferable for patients with veins that are difficult to cannulate and for those who are going to receive rounds of treatment. These central access devices include peripherally inserted central catheter, or commonly known as ‘PICC’ lines, which are inserted into the peripheral vein and advanced up so that the tip of the line sits just above the right atrium of the heart.
A PICC line is a long, thin, hollow, flexible tube. It is injected into one of the arm’s big veins, above the elbow’s bend, by a nurse or physician. Once the tip is in a sizable vein directly above the heart, it is meant to be continually threaded along the vein.
The PICC line may consist of two or three tiny tubes at times. Within the body, these are united as a single tube, and outside the body, they split into two or three lines. This enables you to receive multiple therapies concurrently.
A Portacath is a similar device except that it does not come out of the skin and instead ends in a small chamber buried underneath the skin and into which the drugs can be inserted. When a patient is meant to receive treatment, the nurse or the physician inserts a needle into the chamber to administer injections or to attach a drip. The portacath remains in place as long as the patient requires medical attention.
In some cases, chemotherapy is administered through infusions into the cerebral spinal fluid that surrounds the spinal cord and is known as intrathecal chemotherapy. Intrathecal chemo is used most often to treat cancers that involve the brain or spinal cord or have a high risk of spreading there.
Chemotherapy Drugs for Different Phases of the Cell Cycle
Chemotherapy drugs can be categorized according to the different phases they target during the cell cycle. Antimetabolites are drugs that interfere with the DNA replication process which occurs during the S phase of the cell cycle.
Antimetabolites change the action of enzymes necessary for protein synthesis and cell metabolism by taking the role of natural chemicals as building blocks in DNA molecules.
Stated differently, they imitate the nutrients required for cellular growth, leading the cell to mistakenly absorb them and ultimately starve to death. The presence of antimetabolites prevents the cells from carrying out vital functions ensuring that the cells are unable to grow and survive.
Taxanes and Vinca Alkaloids block the function of microtubules, which are vital to the process of cell division during the M phase. These medications work specifically by preventing cancer cells from dividing into two separate cells. Examples of plant alkaloids used in chemotherapy are actinomycin D, doxorubicin, and mitomycin.
Some drugs are able to exert their action irrespective of the phase and include alkylating agents as well as antitumor antibiotics. These are referred to as non cell cycle specific drugs.
By directly interfering with DNA, alkylating chemicals can stop a cell from dividing by producing aberrant base pairing, DNA strand breakage, or cross-linking of DNA strands. Alkylating drugs kill cells at different and many phases of the cell cycle, which is why they are typically regarded as cell cycle phase nonspecific drugs.
Alkylating drugs are useful in treating slow-growing malignancies, even though they can be utilized for most forms of cancer. Rapidly proliferating cells are less responsive to alkylating chemicals. Alkylating agents include thiotepa, busulfan, cyclophosphamide, and chlorambucil.
Antibiotics with antitumor properties are also not cycle-specific drugs. Their mechanism of action involves binding to DNA to stop the synthesis of RNA (ribonucleic acid), an essential stage in the production of proteins that are vital for cell viability.
They’re not the same as antibiotics which are meant to treat infections caused by bacteria. Instead, these medications uncoil the genetic strands that comprise DNA, which stops the cell from proliferating. Antitumor antibiotics include bleomycin, mitoxantrone, and doxorubicin.
Drug Resistance
Another key factor in chemotherapy is the development of drug resistance. Many cancers show a good response when they are initially exposed to chemotherapy but later become less and less sensitive. Cancer cells and tumors in general are genetically heterogeneous i.e. a cancer is constantly mutating.
Drug resistance may develop prior to the drug therapy or after various rounds of the therapy. The phenomenon of multidrug resistance occurs after developing resistance to a single chemotherapy drug and then gradually to other anticancer agents that may be structurally similar but have a different mechanism of action. Some possible reason for chemotherapy drug resistance include –
- Some cancer cells that evade the chemotherapy drug’s mechanism, continue to live on and mutate. These resistant cells then multiply and mutate and may even form tumors and may not be as sensitive to chemotherapy agents.
- Multi drug resistance leads to the expression of efflux pumps that allow the cancer cell to pump the drug out of the cell with the help of a molecule called p-glycoprotein.
- Cancer cells may stop taking the drugs because the protein that transports the drug across the cell stops working.
Due to the phenomenon of drug resistance, chemotherapy drugs are often given in combinations. The reasoning behind administering combination drugs is that they may reduce the incidence of developing resistance to any one drug. A malignancy is frequently more prone to develop resistance to other medications if it develops resistance to one or a class of treatments.
Determining Chemotherapy Doses
Chemotherapy drugs are strong medications that result in severe side effects. Low doses may not bring any positive results while higher doses may bring life threatening side effects. Due to this reason oncologists take several factors into account before deciding the appropriate dose for a patient. The overall dose to be administered depends on a patient’s body surface area. Ask your oncologist about how body surface area is measured to get an idea of the dosage that will be administered to you.
It is also important to note that there are several other factors that your oncologist will take into account while determining chemotherapy doses. Chemotherapy doses may be adjusted and depend on other factors such as –
- The type and subtype of cancer
- The stage of the cancer
- Results of other tests on the tumor such as biomarkers.
- The age of the patient
- The patient’s overall health and current medications
- Any other serious health problems (such as heart, liver or kidney diseases)
- Types of cancer treatments administered in the past.
Benefits of Chemotherapy
Depending on your treatment goals chemotherapy can offer you a plethora of benefits. Some of these benefits include –
- Prevents your cancer from spreading.
- Slows down the growth of your cancer.
- Gets rid of or slows down the growth of cancer that has metastasized.
- Chemotherapy can also be used as palliative care. In such a case, the aim of chemotherapy is to ease symptoms of pain. When the cancer has advanced and cannot possibly be controlled then chemotherapy may be administered to improve the quality of life.
Side Effects of Chemotherapy
Since chemotherapy attacks both cancer cells and healthy cells of the body, they can cause some severe side effects. Due to the cytotoxic nature of these drugs, these drugs can result in severe side effects. Oncologists will consider these side effects before considering your chemotherapy dose. Some of the commonly experienced side effects seen in chemotherapy include –
- Hair Loss.
- Fatigue.
- Mouth and Throat Sores.
- Diarrhea
- Constipation.
- Nausea.
- Vomiting.
Along with this chemotherapy can also result in bone marrow suppression which results in fewer blood cells being made in the bone marrow. While these side effects may be intimidating, it is important to remember that a patient will not experience every single one of these side effects and their severity also varies depending on the dosage, staging and overall health of a patient. Along with this, there are various drugs available for the management of these side effects. A patient should consult their oncologist for the management of these side effects.
Final Note
Chemotherapy is one of the standard lines of treatment for various cancer types. Patients should try and seek their oncologist’s advice and clarify any queries regarding the treatment as it can significantly help them to understand how this line of treatment works.
