Taxane Chemotherapy

Treating Cancer with Chemotherapy

Cancer is usually treated with a combination of chemotherapy, surgery and radiation. With surgery, a doctor will make an incision in the body and physically remove tumors, sections of organs, or glands (such as the prostate gland or lymph nodes) which have cancerous cells in them. Radiation uses high energy waves, such as gamma rays or x-rays which are targeted directly at cancerous areas in order to kill them.

Chemotherapy is actually a broad medical term for the administration of a any drug to treat any disease within the body. Conversationally, however, it is almost always used to refer to the chemical treatment of cancer. There are a few reasons why chemotherapy might be used, either on its own or in conjunction with the other therapies used to address cancer. Both radiation and surgery target specific areas of the body, such as the liver, the prostate, or the breast. Drugs administered in chemotherapy, on the other hand, will spread throughout the entire body, targeting cancerous cells in multiple areas. It is therefore commonly used when the cancer is thought to have spread (metastasized) from the primary or original cancerous area to other parts of the body.

Chemotherapy, encompassing hundreds of different drugs developed for the treatment of cancer, can be used to help reduce or cure cancer, or simply to provide pain relief or “palliative” care for a cancer patient if no cure is possible. Most doctors are careful never to imply that a cancer drug will certainly cure a patient's cancer or significantly extend their lives because every case is different. Therefore, most cancer drugs are associated with statistics regarding rate of recovery, life expectancy, and improved quality of life. Single chemotherapy drugs can be used on their own, but doctors often prescribe multiple drugs to manage the aggressive symptoms that chemotherapy can cause and to maximum the treatment's efficiency.

When used in conjunction with other treatments, chemotherapy can do a variety of things. Since cancer involves the uncontrolled division and proliferation of cells in the body, chemotherapy works by slowing or stopping the growth of cancer cells and attacking the cells that divide too quickly. It can therefore help shrink tumors before radiation or surgery is attempted, in a process called “neoadjuvant chemotherapy.” Alternatively, it can be used after surgery or radiation therapy as an additional measure to target any cancerous cells that might remain within the body. This second process is known as “adjuvant chemotherapy.”

Categories of Chemotherapy Drugs

There are six primary categories of chemotherapy drugs, although there are some drugs which do not fall into these groupings.

Alkylating Agents

There are many different categories of this particular group of drugs, but their mechanism of operation is similar. They work by targeting and disrupting DNA, the molecule which encodes information in the cell. This keeps the cell from successfully reproducing.

Antitumor Antibiotics

These drugs, like alkylating agents, attack DNA at the cellular level, but they target cancer cells instead of all fast-growing cells in the body. They are the natural products of a species of soil fungus called Streptomyces. They disrupt the enzymes that are necessary for DNA reproduction.

Antimetabolites

Antimetabolites also target cell division, and work effectively because they are so similar to substances that already exist naturally within the human cell. They actually substitute themselves for the compounds in RNA and DNA necessary for cell division, so the chromosomes (columns of DNA) are damaged while being copied.

Topoisomerase Inhibitors

This class of chemotherapy drug is very specific. It targets specific kind of enzyme which is necessary for cell division, either topoisomerase I or topoisomerase II. This specific enzyme helps to separate DNA into two strands so it can be copied. Without correct topoisomerase enzyme function, the cell cannot replicate.

Mitotic Inhibitors or Plant Alkaloids

These drugs are originally derived from plants such as periwinkle, yew, or the May apple plant, although today many of them are produced synthetically. They function primarily by attacking phases of cell division that are not connected to successful DNA replication (which most other classes target). This tends to kill cells which divide quickly, such as cancer cells. Taxanes are part of this group.

Corticosteroids

Many people may have received steroids outside of chemotherapy use. However, since they are commonly used in tangent with other chemotherapy drugs, they are viewed often as a class of chemotherapy prescriptions. They are a class of hormones or hormone-like substances that can prevent allergic reactions, nausea, and vomiting which is associated with chemotherapy.

Other Drugs

There is a wide variety of other drugs that can be used either in addition to the previous or in place of them, depending on the specific cancer, stage, and location in the body. These include various kinds of immunotherapy, enzyme treatments, and differentiating agents, which work to turn cancer cells back into mature normal cells.

Taxane or Taxoid Treatments

Taxanes or taxoids are a subclass of mitotic inhibitors, meaning that they were originally derived from plants which are part of the genus “Taxus,” a group which includes small trees and shrubs in the yew family. Taxanes and taxoids are generally defined identically, with slight variation depending upon the reference. This class includes two major chemical derivatives.

Paclitaxel

Paclitaxel is the nonproprietary name for the drug which is sold under the trade names Taxol and Abraxane, among others. It is most commonly used to treat a variety of cancers such as Kaposi's sarcoma, breast, ovarian, lung, bladder, prostate, melanoma, esophageal, and other types of solid tumor cancers. This chemical was isolated in 1971. Until 1993, paclitaxel could only be obtained through extraction from the bark of yew trees in the Pacific Northwest. After decades of research, however, a synthetic version is in production which is grown by cell culture.

Docetaxel

Docetaxel, which is sold under the brand name of Taxotere, is also used to treat many kinds of cancer, such as breast cancer, head and neck cancer, stomach cancer, prostate cancer and non small-cell lung cancer. Docetaxel was synthesized and patented in 1986 and approved for medical use nearly ten years later, in 1995.

Early History of Taxanes

In 1962, the National Cancer Institute was in the midst of a program which requested that researchers around the county collect biological samples from different organisms in order to test and evaluate their usefulness in pharmaceutical development. A botanist from the US Department of Agriculture, Arthur Barclay, obtained a sample of a yew tree from a state forest in Washington. By 1967, two researchers in North Carolina, where the sample had been sent, had isolated the active ingredient, which they called taxol. However, the drug was difficult to harvest and isolate, and researchers believed early on that there were preexisting synthetic alternatives that worked just as well in fighting cancer.

Starting in 1978, two different researchers in New York took up the research on taxanes in chemotherapy again, and soon realized that the agent attacked cancer in a completely novel way, by targeting the microtubules of a cell which was completely unprecedented. Chemical companies wanted to take advantage of the drug, but Pacific Northwest yew populations were only estimated to last five years with the rate of predicted extraction. Taxanes are particularly complicated to synthesize because they do not dissolve in water and because they are highly asymmetrical. Taxol contains a whopping 112 atoms which much be synthesized perfectly.

It wasn't until 1994 that taxol was successfully synthesized. After taxol was created, scientists started experimenting with varieties of the drug with small changes. They wanted to see if the drug could be made more effective or produced more economically. The “first notable taxoid” or derivative of taxol was Docetaxel, or Taxotere, which is different that the original at two sites of the compound's structure. Today, there is some debate as to the comparative effectiveness of the two kinds of taxanes. Some people believe their function is nearly identitical, while others note small differences in treatment outcomes.

In Depth: How Taxanes Function within the Body

Paclitaxel and Docetaxel work in the body in similar ways and through a nearly identical mechanism of action. In order to understand how the drug functions, however, it is necessary to review the makeup of a human cell. Within the membrane of a cell, there is the cytoplasm, which includes all the internal “organelles” or components of the cell, such as the nucleus, the mitochondria, and the ribosomes. All of these structures are suspended in a combination of jelly-like substance, called cytosol, and the cytoskeleton, a network of intertwined tubes and filaments.

Three substances which make up the cytoskeleton, the structural integrity of the cell, include microfilaments, intermediate filaments, and microtubules. Taxanes directly affect the functioning of the microtubules. Microtubules and composed of protein and actually have three functions within the body of the cell. They are there for structural support (as part of the cytoskeleton), they help the cell to move and contract, similar to muscle function in larger organisms, and they provide pathways for transmission of chemicals between different organelles within the cell, like a system of highways. Microtubules are also always in flux, meaning that they are being lengthened or shortened in a process known as “polymerization” for adding or “depolymerization” for detracting length.

Since microtubules can grow and shrink, they are essential for the process of cell division and the restructuring of the cell that takes place during that division, or mitosis. Taxanes are chemicals which halt the process of polymerization and depolymerization by stabilizing the ends of the microtubules. This stabilization essentially freezes these dynamic components of the cell and prevents the process of division, which is necessary for the spread and development of cancer.

In addition, taxanes may actually cause cell death, or “apoptosis.” This pre-programmed process of natural cell death is often arrested or inhibited by cancer, meaning that cancer cells will not naturally die as quickly as other cells. Taxanes can help restore the process of cell death in cancer cells. This consequence occurs either as a secondary effect of stabilizing and freezing microtubules, or because the taxane manages to switch off a protein that blocks apoptosis in cancer cells.

Side Effects of Taxane

Because taxanes are designed to indiscriminately halt and sometimes kill cells which grow and divide quickly, their side effects stem from their influence on other kinds of fast-growing cells in the body. That is, since they target a specific stage of the cell division process, they are deadly or “cytotoxic” to a certain extent, for all cells in the body, but they are more toxic or deadly to the kinds of cells that divide quickly, such as tumor cells, bone marrow cells, and hair follicle cells (which is why chemotherapy patients often lose their hair).

Taxanes, like many chemotherapy drugs, therefore generally cause problems with the body's systems that rely on quickly dividing cells. Lack of white blood cells or bone marrow cells affects the body's immune system and makes it less able to fight off diseases and infections. It can also cause side effects as varied and extreme as nausea and vomiting, fever, exhaustion, skin rash, sore throat, chest pain, and pain in the joints, among others.

In addition, there is growing evidence that Taxotere, the alternative formulation of the original taxol substance, can cause permanent hair loss in some cases. This is called Alopecia, and is found in higher incident rates in patients who receive Taxotere than in other chemotherapy drugs. The rate of incidence was not originally publicized as a common side effect of the product, and the drug has therefore come under a great deal of legal and moral scrutiny in the past few years as the effects become more widely recognized.

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