CHEMOTHERAPY RESEARCH CASE STUDY
The aim of this paper is to follow a cancer patient named John through his oncology/chemotherapy journey. John is a 54 year old married man with three grown up children. He just had surgery for bowel cancer and has been referred to an oncologist for oxaliplatin and 5-Fluorouracil (Fu) chemotherapy. A course of 6 treatments – 3 weekly has been prescribed. John will have a hickman lin inserted to enable him to have the oxaliplatin in the chemotherapy unit and the 5 Fu attached to a Baxter ambulatory pump, enabling him to be at home with his family. He will return to the unit in 48 hours time to have the pump removed. The line will need to be flushed weekly with a heparin based saline to maintain its patiency.
John is assessed for peripheral sensory neuropathy. Acute onset occurs within hrs to 1–2 days of dosing, resolves within 14 days, and frequently recurs with further dosing (transient paresthesia, dysesthesia and hypothesia of hands, feet, perioral area, or throat). Symptoms may be precipitated or exacerbated by exposure to cold or cold objects. It may also cause jaw spasm, abnormal tongue sensation, dysarthria, eye pain, and a feeling of chest pressure. Persistent (>14 days) causes paresthesias, dysethesias, and hypoesthesias, but may also include deficits in proprioception that may interfere with daily activities (walking, writing, swallowing). Persistent neuropathy may occur without prior acute neuropathy and may improve upon discontinuation of oxaliplatin.
John is assessed for signs of pulmonary fibrosis (non-productive cough, dyspnea, crackles, radiological; infiltrates). Any sign of these may be fatal. Oxaliplatin should be discontinued if pulmonary fibrosis occurs. Patients should be monitored for signs of anaphylaxis (rash, hives, swelling or lips or tongue, sudden cough). Epinephrine, corticosteroids, and antihistamines should be readily available. White blood count is monitored with differential, hemoglobin, platelet count, and blood chemistries (ALT, AST, bilirubin, and creatinine) before each oxaliplatin cycle.
Extravasation may result in local pain and inflammation that may be severe and lead to necrosis. John is premedicated with antiemetics with or without dexamethasone. Prehydration is not required.
Intermittent Infusion is reconstitute by adding 10 ml for the 50 mg vial or 20 ml for the 100 ml vial of sterile water or D5W. It is not advisable to reconstitute with NaCl solution. It must be further diluted with 250–500 ml of D5W. Aluminum needles or administration sets containing aluminum parts were not used as aluminum may cause degradation of platinum compounds. It may be stored in refrigerator for 24 hr or 6 hr at room temperature. The solution is not light-sensitive. Solutions that are discolored or contain particulate matter are not administered. Oxaliplatin is administered simultaneously with leucovorin in separate bags via Y-line over 120 min.
Y-Site Incompatibility: Alkaline solutions, chloride-containing solutions. Infusion line should be flushed with D5W prior to administration of other solutions or medications.
John and his caregivers (his children) are informed of potential for peripheral neuropathy and potentiation by exposure to cold or cold objects. John is advised to avoid cold drinks, use of ice in drinks or as ice packs, and to cover exposed skin prior to exposure to cold temperature or cold objects. John is also cautioned to cover himself with a blanket during infusion, not to breathe deeply when exposed to cold air, wear warm clothing, and cover mouth and nose with a scarf or pull-down ski cap to warm the air that goes to their lungs, not to take things from the freezer or refrigerator without wearing gloves, drink fluids warm or at room temperature. He is also cautioned to always drink through a straw, not to use ice chips for nausea, to be aware that most metals (car doors, mailbox) are cold; to wear gloves to touch, not to run air conditioning at high levels in house or car, and if his hands get cold wash them with warm water. John and his children are advised to inform health care professional of how John did since last treatment before next infusion.
John is instructed to notify health care professional immediately if signs of low blood cell counts (fever, persistent diarrhea, infection) or if persistent vomiting, signs of dehydration, cough or breathing difficulty, thirst, dry mouth, dizziness, decreased urination or signs of allergic reactions occur.
The word cancer elicits dread in nearly everyone. Cancer accounts for considerable mortality and morbidity in both men and women ( 2004). Certain genes controlling growth and interactions with other normal cells are apparently abnormal in structure or regulation in cancer cells. Humans of all ages develop cancer, and a wide variety of organs are affected. The incidence of many cancers increases as the fourth to sixth power of age, so that as people live longer, many more will develop the disease. Apart from individual suffering, the economic burden to society is immense (2000).
Cancer of the large bowel is relatively common in persons older than 50 years. The growth is restricted to the bowel wall for a considerable time before it spreads via the lymphatics. Bloodstream spread via the portal circulation to the liver occurs late. If diagnosis is made early and a partial colectomy is performed, accompanied by removal the lymph vessels and lymph nodes draining the area, then a cure can be anticipated (2000).
Cancer cells are characterized by three properties: (1) diminished or unrestrained control of growth; (2) invasion of local tissues; and (3) spread, or metastasis to other parts of the body. Cells of benign tumors also show diminished control of growth but do not invade local tissue or spread to other parts of the body (2000).
Cancer is caused in all or almost all instances by mutation or by some other abnormal activation of cellular genes that control cell growth and cell mitosis. The abnormal genes are called oncogenes. Cancer tissue competes with normal tissues for nutrients. Because cancer cells continue to proliferate indefinitely, their number multiplying day by day, one can readily understand that the cancer cells soon demand essentially all the nutrition available to the body or to an essential part of the body. As a result, normal tissues gradually suffer nutritive death ( 2000).
An abnormal cell mass that develops when controls of the cell cycle and cell division malfunction is called a neoplasm. However, not all neoplasms are cancerous. Benign neoplasms are strictly local affairs. They tend to be surrounded by a capsule, grow slowly, and seldom kill their hosts if they are removed before they compress vital organs. In contrast, malignant (cancerous) neoplasms are nonencapsulated masses that grow more relentlessly and may become killers. Their cells resemble immature cells, and they invade their surroundings rather than pushing them aside, as reflected in the name cancer from the Latin word for “crab.” Malignant cells also tend to spread via the blood to distant parts of the body, where they form new masses. This last capability is called metastasis (2004).
Genetic aspects of cancer are probably receiving the greatest current attention among genetic abnormalities. Some cancers are caused by oncogenes, genes which are carried in the genomes of cancer cells and are responsible for producing their malignant properties. These genes are derived by somatic mutation from closely related proto-oncogenes, which are normal genes that control their growth. Over 100 oncogenes have been described (2001).
Obviously, the initiation of mitosis and normal cell division depends on the orderly occurrence of events during what has come to be called the cell cycle. There is intense interesting the biochemical machinery that produces mitosis, in part because of the obvious possibility of its relation to cancer. When DNA is damaged, entry into mitosis is inhibited, giving the cell time to repair the DNA; failure to repair damaged DNA leads to cancer. The cell cycle is regulated by proteins called cyclins and cyclin-dependent protein kinases, which phosphorylate other proteins ( 2001).
Cell replication involves not only DNA polymerase but a special reverse transcriptinase that synthesizes the short repeats of DNA that characterize the ends (telomeres) of chromosomes. Cells with high telomerase activity, which includes most cancer cells, can in theory keep multiplying indefinitely (2001).
Cell Division in normal and cancer cells.
The stepwise development of a typical colon cancer is as follows:
1
2
3
Cellular changes
Increased cell division
Growth of polyp
Growth of malignant tumor (carcinoma)
DNA changes
Oncogene activated
Tumor-suppressor gene activated
Second tumor-suppressor gene activated
The treatment of choice for either type of neoplasm is surgical removal. If surgery is not possible – as in cases where the cancer has spread widely or is inoperable – radiation and drugs (chemotherapy) are used. Chemotherapeutic drugs destroy malignant cells (2004).
After major bowel surgery, an outpatient appointment (for approximately six weeks) will be sent to you in the post. Some patients who have surgery for bowel cancer can benefit from additional treatment (called adjuvant therapy) in the form of chemotherapy or radiotherapy and, therefore, might receive an appointment to see the oncologists (who treat patients with cancer).
As previously stated, when chemotherapy or radiotherapy is used in addition to surgery it is known as ‘adjuvant chemotherapy’ or ‘adjuvant radiotherapy’. For example, following surgery you may be given a course of chemotherapy or radiotherapy. This aims to kill any cancer cells which may have spread away from the primary tumor site. This is the kind of therapy that John underwent. Sometimes, adjuvant chemotherapy or radiotherapy is given before surgery to shrink a large tumor so that the operation to remove the tumor is easier for a surgeon to do, and is more likely to be successful.
Cytotoxic therapy regimens are highly toxic to cells, and can result in a range of acute and chronic adverse effects for persons receiving these treatments (1996). A number of these adverse effects are potentially life threatening. The safe and effective delivery of these drugs therefore requires highly complex clinical assessment, technical and problem solving skills.
Cytotoxic agents can be administered in a variety of ways, including: Oral (by mouth), Topical (on the surface of the skin as a cream or lotion), Intravenous (into a vein or IV), Intramuscularly (into a muscle or IM), Subcutaneous (under the skin or SQ), Intra-arterial (into an artery), Intrathecal (into the central nervous system via the cerebrospinal fluid), Intrapleural (into the chest cavity), Intraperitoneal (into the abdominal cavity), Intravesical (into the bladder) and Intralesional (into the tumor) ().
The term parenteral is used to describe drugs given intravenously, intramuscularly, or subcutaneously. The intravenous route is most often used. Intramuscular and subcutaneous injections are used less often because many drugs can be very irritating or even destroy skin or muscle tissues. Giving cytotoxic drugs via an IV route gets the drugs quickly throughout the body. IV therapy may be given through a vein in the arm or hand or through a vascular access device (VAD), using a catheter implanted into a larger vein in the chest, neck, or arm. VAD’s are used in cancer treatment to give several drugs at the same time, for long-term chemotherapy, for continuous infusion therapy, and to give vesicants (drugs that can destroy tissues if an IV infiltrates).
Many cytotoxic agents can cause severe tissue damage if an IV needle or catheter delivers the drug into tissues rather than into the bloodstream. The term extravasation is used when a cytotoxic drug infiltrates into local tissues. Some drugs, known as irritants, can cause local cellular damage. Other drugs, referred to as vesicants, can cause severe tissue damage requiring skin grafting. To avoid infiltration with vesicant drugs, the larger veins of the arm are used for IV administration. Drugs that are classified as vesicants include cisplatin, dactinomycin, daunorubicin, doxorubicin, idarubicin, mechlorethamine, mitomycin-C, mitoxantrone, paclitaxel, vinblastine, vincristine, vindesine, vinorelbine, and 5-fluorouracil. In some instances, locally applied antidotes may help minimize the effects of infiltration ().
Surgery, radiotherapy, and chemotherapeutic agents are the major modalities used to treat patients with cancer, though various biologic therapies are beginning to have a significant impact. The basic problem is to make available drugs (natural products or synthetics) that kill cancer cells effectively but are not excessively toxic to normal cells. The table below lists seven major classes of compounds that have been widely used in the treatment of cancer:
Class of Compound
Example
Site of Action
Treatment Use
Alkylating agents
Melphalan
Alkalytes DNA and other molecules
Myeloma
Antimetabolites
Purine antagonists
Pyrimidine antagonists
Folate antagonists
Mercaptopurine
Fluorouracil
Methotrexate
Converted to a “fraudulent” nucleotide and inhibits purine synthesis
Converted to a “fraudulent” nucleotide and inhibits thymidylate synthetase
Inhibits dihydrofolate reductase
Acute myelocytic leukemia
Colorectal cancer
Choriocarcinoma
Antitumor antibiotics
Doxorubicin
Intercalates in DNA and stabilizes the DNA-topoisomerase II complex
Hodgkin’s disease
Other agents
Cisplatin
Hydroxyurea
Causes strand breakage in DNA
Inhibits ribonucleotide reductase
Carcinoma of the lung
Chronic myelocytic leukemia
Plant compounds
Vinblastine
Binds tubulin and inhibits microtubule formation
Kaposi’s sarcoma
Sex hormones
Estrogens
Block effects of androgens in prostatic tumors
Cancer of the prostate
Corticosteroids
Prednisone
Inhibits proliferation of lymphocytes
Myeloma
Insofar as unrestrained cell division is a feature that typifies many malignant tumors, many of these agents are used because they inhibit DNA synthesis. For this reason, they are also likely to damage normal tissues whose cells divide continuously – e.g. bone marrow (2000)
The growth fraction (percentage of the cells of a tumor that are constantly in cycle) is an important concept in cancer chemotherapy; tumors with a high growth fraction are usually more responsive to cancer chemotherapy than cells that are dormant in the G phase of the cycle. It is useful to classify anti-cancer drugs as cell cycle-specific (CCS) or cell cycle-nonspecific (CCNS). CCS includes fluorouracil and methotrexate, and acts on proliferating cells. CCNS includes alkylating agents and cisplatin, and acts irrespective of the state of proliferation (2000).
Oxaliplatin is used in combination with 5-Fluorouracil and leucovorin in the treatment of metastatic colon or rectal cancer that has progressed despite treatment with first-line agents. It inhibits DNA replication and transcription by incorporating platinum into normal cross-linking (cell cycle nonspecific). It causes death of rapidly replicating cells, particularly malignant ones ( 2004).
Anti-cancer drugs have unpleasant side effects because most target all rapidly dividing cells, including normal ones. The side effects include nausea, vomiting, and loss of hair. X rays also have side effects because, in passing through the body, they kill healthy cells that lie in the path to the cancer cells (2004). Life threatening adverse reactions and side effects of the treatment include pulmonary fibrosis and anaphylaxis/anaphylactoid reactions. The most frequent includes fatigue, diarrhea, nausea, vomiting, anemia and neurotoxicity (2004).
Current cancer treatments – “cut, burn, poison” – are recognized as crude and painful. Promising new methods focus on delivering anticancer drugs precisely to the cancer (via monoclonal antibodies that respond to one type of protein on a cancer cell) and on increasing the immune system’s ability to fend off cancer ( 2004).
Chemotherapy can produce the following actions: risk for deficient fluid volume, imbalanced nutrition-less than body requirements, impaired oral mucous membrane, disturbed body image, and ineffective protection ( 2004).
Risk factors for deficient fluid volume may include gastrointestinal losses (vomiting), interference with adequate intake, losses through abnormal routes (indwelling tubes, wounds) and hypermetabolic state (2004).
Imbalanced nutrition may be related to inability to ingest adequate nutrients, hypermetabolic state, possibly evidenced by weight loss, aversion to eating, reported altered taste sensation, diarrhea and/or constipation (2004).
The impaired oral mucous membrane may be related to side effects of therapeutic agents, dehydration, and malnutrition, possibly evidenced by ulcerations, leukoplakia, decreased salivation, and reports of pain (Doenges & Moorhouse, 2004).
Disturbed body image may be related to anatomical/structural changes; loss of hair and weight, possibly evidenced by negative feelings about body, preoccupation with change, feelings of helplessness/hopelessness, and change in social environment ( 2004).
Ineffective protection may be related to inadequate nutrition, drug therapy/radiation, abnormal blood profile, disease state (cancer), possibly evidenced by impaired healing, deficient immunity, anorexia and fatigue ( 2004).
For cancer of the colon, radiotherapy is not routinely used, but if examination of cells from the removed cancer shows that the cancer has spread to lymph glands, then some form of chemotherapy will normally be given, usually oral 5-fluorouracil. Chemotherapy is very likely to cause side effects, including nausea and hair loss, but the nausea can usually be well controlled by drugs (2005). Cancer pain syndromes can result from the progression of the disease or from efforts to cure or control the disease (2004).
In all these, the senior oncology / colorectal specialist nurses is responsible for co-ordinating care following any operations and/or treatment for bowel cancer. A senior oncology nurse is highly qualified, having specialized training in caring for patients who have bowel disease, and has many years of experience in this field. As well as supporting John and his family through his operation and treatment, the senior oncology nurse provides John and his caregivers with clear written and verbal information; and can also examine John and arrange any tests he might need.
The number of patients suffering from cancer has steadily increased in recent years mainly due to an ageing population. Add to this, an increasing number of chemotherapeutic agents and a multitude of regimes, it therefore becomes imperative to educate the nurse on the care of the chemotherapy patient.
The NHS Cancer Plan, published in September 2000, sets out the first ever comprehensive strategy to tackle the disease. It is the first time any government has drawn up a major program of action linking prevention, diagnosis, treatment, care and research. The NHS Cancer Plan contains a wide range of targets and commitments. The NHS Cancer Plan Progress Report released in March 2005 substantial progress has been made in meeting the Plan’s targets. The thirty-four cancer networks which have been established have achieved important improvements in delivering cancer services across England (2005).
The progress report also mentioned that cancer networks have helped improve cancer services and have achieved some particular successes. These include planning for the introduction of new cancer drugs and developing plans for funding specialist palliative care. In addition to the NHS Cancer Plan, the Department has launched other initiatives to improve cancer services, including a tobacco advertising ban and a strengthening of the partnership between the NHS and the voluntary sector (2005).
The effectiveness of John’s therapy is demonstrated by the decrease in size and spread of his cancer malignancies.
Credit:ivythesis.typepad.com
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