The Use of Chemotherapy in Cancer - Research Proposal Example

Running Head Chemotherapy The Use of Chemotherapy in Cancer Cancer ranks as the second leading cause of mortality next to heart disease. It happens when the normal cycle of cell growth is disrupted, which gives rise to undifferentiated cells of abnormal morphology. Cancer treatments come in several forms. It may be through surgery, radiation therapy, biological therapy, or through the use of a drug or combination of drugs which act synergistically to get rid of the cancer cells, a process known as chemotherapy. Dating back to the 17th century, the use of chemotherapy has proven to be of great benefit to patients who opt to undergo this treatment. Chemotherapy continues to improve throughout the years. In this paper, the author examines chemotherapy by looking not only at its history, but at its current developments and its future use. Incidence of Cancer In 2004, a total of one hundred fifty three thousand three hundred ninety-seven (153,397) individuals died of cancer in the United Kingdom; 22% of which is caused by lung cancer, 11% by bowel cancer, 8% by breast cancer, 7% by prostate cancer and the rest (52%) by other forms of cancer. Among all other forms, lung cancer and breast cancer still rank as the most common forms of cancer in males and females, respectively. Trends in the incidence of cancer in the UK is an indication of the success of the campaigns against the disease as the figures show a decreasing mortality rate despite the increase in the incidence of the disease (Cancer Research UK Information Resource Centre, 2006). In the United States on the other hand, the National Center for Health Statistics has in 2003 named malignant neoplasms, or cancer as the second leading cause of death following diseases of the heart. This is despite the fact that there has been a decline in cancer death rates from 1993-2002, as reported by the National Cancer Institute on the 2005 Update of Cancer Trends Progress Report. This paper is aimed at exploring the facts on the efficacy and the future of chemotherapy in the quest for cure for cancer. The National Cancer Institute defined cancer as a group of many related diseases. It starts when the process of cell differentiation takes on an abnormal pattern. Healthy cells usually grow and divide when the body needs them, and the death of some cells would be the signal for the production of new ones. When this pattern is disrupted and cells grow when they shouldn’t and they don’t die when they should, they form a mass of tissue called a growth or a tumor. Tumors can either be benign and do not spread to other nearby tissues, or they can be malignant or cancerous and metastasize or spread to the other parts of the body. Treatment for malignant cancers can be in the form of chemotherapy, radiation therapy, biological therapy, hormone therapy, surgery, cryosurgery or a combination of these. History of Chemotherapy Contrary to what most people know, chemotherapy is a general term used to refer to any drug that is used to treat any disease, rather than treating cancer alone. Other names used to refer to cancer chemotherapy are antineoplastic (anticancer) therapy, and cytotoxic (cell-killing) therapy (Chemotherapy Principles, 2005). The ability of chemotherapeutic drugs to go into the systemic circulation is what sets it apart from the other types of treatment making it a top choice in treating cancer. Its beginnings can be traced to as far back as the 17th century. During that time, cancer has already been identified to start as a lesion that grows by destroying other surrounding cells. A compilation of the available treatments was published in 1712 which included 2 drops of Tinctura vitriolata, and a solution of alkali such as camphor, chalk, gold, silver and salts of lead that correct the accumulation of malignant acids. One particular prescription proved to be quite beneficial at that time. It was made up of 1 scruple crab’s eye, 1 scruple red coral, 15 grains of salt of tartar, 12 drops of oils of cloves, 12 drops of oil of cumin and 5 grains of opium. The mixture was fermented to powder and divided into seven doses, given at one dose a day. By the 1800s, the use of pure chemicals as therapeutic agents had slowly been introduced. Some of the known remedies included pate of arsenic, nitrate of mercury, and solution of conium as published by Recamier in 1829. An increased interest in chemotherapy arose in the second half of the 19th century when Louis Pasteur, Robert Koch and Joseph Lister, who were pioneers in pathobiology, bacteriology and chemotherapy of infectious diseases, demonstrated that microorganisms that cause infectious diseases can be killed through chemotherapy. Meanwhile, Paul Ehrlich, a contemporary of Lister and a disciple of Koch, discovered that methylene blue can be absorbed by certain parts of a cell while leaving other parts unstained. He applied his staining methods to distinguish between lymphoid and myeloid cells in the bone marrow and later coined the term myeloid leukemia. This was followed by his discovery of the arsenical compound salvarsan as an effective agent against syphilis and trypanosomiasis. He later won a Nobel Prize which he shared with Metchnikoff in 1908 for his work on serum therapy and cellular immunity. It was also during this time when he very much into the field of immunology and the chemical effect of paramidobenzol, phenylarsenoxyl, diamidoarsenobenzol, and pyocyanase on carcinomas and sarcomas. His application of the old Paracelsian idea of specific remedies for specific diseases led him to the idea that cancerous cells can be damaged by chemicals without harm to the healthy host tissues. He then summarized his observations in a book known to be the first book in chemotherapy. In 1921, trypsin and amylopsin were introduced in the United States as new treatments for cancer. In 1925, it was discovered that the injection of urathan in rabbits and rats decreased circulating lymphocytes. The arousal of national interest on cancer was then expressed in 1937 when the National Cancer Act was passed by the Congress. The discovery of the first drug used for chemotherapy was quite accidental. Mustard gas, which was used as a tool in chemical warfare in World War I was found to have caused low levels of lymphocytes in people who were accidentally exposed to it. This observation led to the introduction of nitrogen mustard in 1942 as a chemical agent to treat lymphomas and leukemias. Further, it was found that inostol and folic acid, which are naturally occurring substances, inhibited the growth of breast cancer in mice leading scientists to think of their suitability for chemotherapy in humans. By the end of the Second World War in 1946, the American Association for Control of Cancer was reorganized into what we now know as the American Cancer Society. In 1948, the remission of acute leukemia in children was achieved with the use of folic acid antagonists. With these developments, the period of modern chemotherapy emerged in the 1950s, and in 1956, methotrexate was announced to be an effective agent against choriocarcinoma of the uterus in humans (2000 Years of chemotherapy of tumors, 2005). The Current Use of Chemotherapy The American Cancer Society was established in 1946 to help cancer patients cope with the disease. They initiated programs and campaigns to promote awareness among cancer patients, but to their families as well in their belief that cancer does not affect the patient alone, but also all the people surrounding the patient such as his/her family and loved ones. Today the American Cancer Society hosts a comprehensive site for all those who want to learn more about the disease. The following discussion is taken from the discussions on chemotherapy by the ACS (Chemotherapy Principles, 2005). The study of how chemotherapy works requires a basic knowledge of the stages of cell development. These stages include the G0 or the resting stage, G1 or RNA and protein synthesis stage, the S phase or the DNA synthesis stage, G2 or the construction of mitotic apparatus stage and the M phase or the mitosis stage. The resting stage is the latent phase of the cell cycle. It can last for hours or even years in some cells. Cells in this phase readily go to the second stage once stimulated. The second stage (G1) lasts for 18-30 hours. Here the cells manufacture more proteins and get ready to divide. The S phase marks the replication of the genetic material known as the deoxyribonucleic acid or DNA, so that the daughter cells would each have the same amount of genetic material. This phase lasts for about 18-20 hours. The G2 phase happens just before the cell starts to divide and lasts for 2-10 hours. The M phase marks the actual division of the cell, producing 2 daughter cells with the same genetic make-up. It is important that the physician knows the stages of cell development because chemotherapeutic drugs work only on actively dividing cells and may act only on specific stages of the cell cycle. A knowledge of the cell cycle would therefore guide an oncologist on how these drugs should be administered, how often they should be administered and what drugs could be co-administered with another. Because chemotherapeutic drugs work on actively dividing cells, they inadvertently hit the normal functioning cells as well, as they are unable to tell the difference between cancer and healthy cells. This event is what causes the adverse reactions associated with chemotherapy. Below is an illustration of how cancer cells in the epithelial tissues would look like: Epithelial tissues cover the human body and line its internal cavities of major organs like the skin, breast, pancreas, intestines, lung, prostate and thyroid gland. Cancer of the epithelial tissues, called carcinoma, can easily spread throughout the body via the lymphatic system (Cancer picture, 2005). Chemotherapy treatment generally has three possible goals. These may be 1) to cure the disease which involves the complete eradication of the cancer cells, 2) to control the disease from growing and spreading to the other parts of the body thereby extending and improving the life of the patient, and 3) palliation, or the use of chemotherapy to relieve the symptoms associated with the disease and improve the quality of life of the patient without necessarily prolonging it. This is true for advanced-stage cancers. Chemotherapy can also be given alongside the other treatments like surgery or radiation therapy. It may be used as a neoadjuvant therapy or as an adjuvant therapy. As a neoadjuvant therapy, chemotherapy works by reducing the size of the tumor cells in order to decrease the need for an extensive type of surgery or radiation therapy. As an adjuvant therapy, chemotherapy works as means to get rid of stray tumor cells which are still present but are not visible under diagnostic tests like CT scans. There are several types of drugs used in chemotherapy. These are 1) alkylating agents, 2) Nitrosoureas, 3) Antimetabolites, 4) Anthracyclines, 5) Topoisomerase II inhibitors, 6) Mitotic inhibitors, and 7) Corticosteroid hormones. Alkylating agents prevent the further replication of the DNA to prevent the reproduction of the cancer cells. These agents are not stage-specific, hence could be given at any time during the treatment. These drugs are active against chronic leukemias, non-Hodgkin lymphoma, Hodgkin disease, multiple myeloma, and lung, breast, ovarian, and certain other cancers. Some examples of alkylating agents include busulfan, cisplatin, carboplatin, chlorambucil, cyclophosphamide, ifosfamide, dacarbazine (DTIC), mechlorethamine (nitrogen mustard), melphalan, and temozolomide. Nitrosoureas, like alkylating agents, interfere with the enzymes that help repair DNA. These drugs are usually used to treat brain tumors as they are the only type of drugs that are able to cross the blood-brain barrier. They may also be used to treat non-Hodgkin lymphomas, multiple myeloma, and malignant melanoma. Examples of nitrosoureas include carmustine (BCNU) and lomustine (CCNU). Antimetabolites work during the S phase and interfere with the DNA and RNA growth. They are commonly used to treat leukemias, tumors of the breast, ovary and the gastrointestinal tract and other cancers. Examples of these drugs are 5-fluorouracil, capecitabine, 6-mercaptopurine, methotrexate, gemcitabine, cytarabine (ara-C), fludarabine, and pemetrexed. Anthracyclines work in all phases of the cell cycle and work by interfering with the enzymes during DNA replication making them widely used for a variety of cancers. A major concern though, when giving these drugs is its effect on the cardiac muscle. Examples include daunorubicin, doxorubicin (Adriamycin), epirubicin, idarubicin, and mitoxantrone. Topoisomerase II inhibitors act on topoisomerase II which is important in DNA replication. They are used to treat certain leukemias, and gastrointestinal, ovarian, lung and other cancers. Some examples would be topotecan, irinotecan, etooside (VP-16), and teniposide. Mitotic inhibitors inhibit the enzymes involved in the production of proteins needed for the reproduction of the cell. These drugs are made up of plant alkaloids and other compounds derived from other natural products. They work during the M phase of the cell cycle. Examples include taxanes such as paclitaxel and docetaxel and the vinca alkaloids such as vinblastine, vincristine, and vinorelbine.Corticosteroid hormones like prednisone and dexamethasone are used in combination with other chemotherapy drugs to increase their effectiveness in killing or slowing down the growth of cancer cells. Some other examples of chemotherapy drugs that do not fall under any classification due to their slightly different mode of action are L-asparaginase, dactinomycin, thalidomide, and tretinoin. In choosing which chemothrapy drug is best for a patient, it is important to consider several factors such as the type of cancer, the stage of the cancer, age, general state of health, other health problems like liver and kidney diseases and other types of anticancer treatments given in the past. It is also important to take note of the other drugs that the patient might be taking concomitantly with chemotherapeutic drugs to prevent any untoward interaction that these drugs may have on each other. Precaution must also be taken when taking vitamins alongside chemotherapy drugs as the antioxidant effect of certain vitamins may interfere with the chemotherapy drugs’ action on producing ions which disrupt DNA production of cancer cells. Chemotherapy is a non-selective process. In its effort to eradicate cancer cells, it inadvertently damages also the healthy cells of an individual, especially rapidly-dividing ones like the cells of the bone marrow, hair follicles, and cells in the digestive and reproductive tract. These healthy cells are supposed to be a part of the individual’s normal physiology and destruction of these would also mean the disruption of the body’s processes. Some of the adverse events brought about by chemotherapy are suppressed immune system due to the decreased WBC count, anemia which is caused by the drop in the RBC count, thrombocytopenia due to the drop in platelet count, nausea and vomiting, hair loss, appetite and weight loss, taste changes, sores in the mouth and throat, constipation, diarrhea, fatigue, heart damage, nervous system changes, changes in thinking and memory, lung damage, changes in reproduction and sexuality, and liver and kidney damage. The numerous adverse events caused by chemotherapy have prodded scientists to find some other cancer treatments which would kill cancer cells while sparing the normal ones. Currently, researches on the use of virus-specific bacteriophages on cancer treatment are underway. Scientists believe that this would address the problem of the severe damages caused by chemotherapy, but would just be as efficacious in getting rid of the cancer cells. Future of Chemotherapy Chemotherapy, along with other agents, is continuously proving to be effective in treating various types of cancer. Further research into these types of treatments demonstrates that new uses and new formulations of chemotherapy are showing high potentials for effectively curing and controlling cancer. New combinations of chemotherapy drugs as well as new delivery techniques are areas currently being looked into as pathways for improving the quality of life of cancer patients. There are new classes of chemotherapy drugs and combinations of such medicines being developed. These come in the form of antibodies, as well as what are referred to as "targeted therapies", and these drugs are proven to have anti-cancer effects. These so-called targeted therapies are specifically developed to focus on and attack a particular target on cancer cells. They may have lesser side effects than standard chemotherapy drugs, and there is a possibility that the former may eventually be used along with the latter. Some drugs such as imatinib mesylate (Gleevec) have already been given approval for use against certain cancers. There are studies that seem to show how targeted therapies may be given with lesser side effects, with the added factor of making them more effective. This is done by attaching drugs to monoclonal antibodies, which are special types of proteins that can be designed to lead chemotherapy medicines directly to the affected area or tumor. If chemotherapy drugs are not attached to these antibodies, the latter can also be used as immunotherapy drugs that serve to strengthen the body’s immunity against cancer cells. Researches into new ways of administering the drugs are being conducted. The efficacy of using smaller amounts of medicine over longer periods of time, in contrast to administering them continuously with special pumps, are being looked into and studied. Liposomal therapy is a type of treatment that involves using chemotherapy drugs that have been enclosed inside liposomes. These synthetic fat globules help the drug make its way into the cancer cells more selectively, with the benefit of decreasing possible side effects such as alopecia, nausea and vomiting. Some examples of liposomal medicines already in use are DaunoXome (the encapsulated form of daunorubicin) and Doxil (the encapsulated form of doxorubicin). Chemoprotective agents are also currently being developed. These agents serve to protect the patient against specific side effects of certain chemotherapy drugs. For example, dexrazoxane can help prevent damage to the heart, amifostine can help protect the kidneys, and mesna serves to protect the bladder. Chemotherapy can be administered in combination with new developmental agents to help overcome drug resistance. Cancer cells, because of their capacity to develop ways to force the drugs out of the cells, often become resistant to chemotherapy. These new agents render the pumps inactive in order to allow the chemotherapy to remain in the cancer cells longer, consequently, making the treatment more effective. The Efficacy of Treatment in Different Types of Cancer Statistics show that the mortality rate among cancer patients is continuously falling, despite the increasing incidence of the disease. This seems to indicate the effectiveness of cancer treatments and programs currently being employed. While there are no available current data on researches as to the efficacy of chemotherapy alone as a cancer treatment, it is safe to assume that several factors contribute to the success of cancer treatments. Early detection is the foremost factor in curbing the mortality rate. Detection, coupled with advancements made on drugs and programs for efficient administering of medicines, contribute notably as well. Chemotherapy undoubtedly figures significantly in the survival rate, and the combination treatments that are advanced along with chemotherapy make the latter much more efficient today. Below is a chart from Cancer Research UK (February, 2006) that shows the changes in percentages of European cancer mortality: It can be noted that advancements in the area of cancer research are proving considerably effective, as evidenced by the increasing options regarding treatment. Increased options translate into more appropriate modes of treatment, hence making such treatments more efficient. Chemotherapy, as one of the major treatments currently available, is one such treatment that has undergone improvements and now shows even greater promise in successfully treating cancer. It will not come as a surprise then, given the positive trends in research and development, that in the next few years cancer treatments will provide even more hope for those who suffer needlessly from cancer. References Chemotherapy principles. (2005). Retrieved Apr. 8, 2006, from Making Treatment Decisions Web site: http://www.cancer.org/docroot/eto/eto_1_3_chemotherapy_principles.asp. 2000 years of chemotherapy of tumors. (2005). Retrieved Apr. 8, 2006, from A note from history Web site: http://www.aboutcancer.com/chemotherapy_history.htm. Cancer picture. (2005). Retrieved Apr. 8, 2006, from Cancer Information and Support International Web site: http://www.cancer-info.com/canpic.htm. Cancer Research UK Information Resource Centre (2006). CancerStats, retrieved April 10, 2006 http//:info.cancerresearchuk.org/cancerstats Read More