Chapter 52: Antineoplastic Drugs Part 1: Cancer Overview and Cell Cycle–Specific Drugs

Lilley’s Pharmacology for Canadian Health Care Practice, 4^th Canadian Edition

Chapter Summary

OVERVIEW

Cancer is a broad term encompassing a group of diseases characterized by cellular transformation (e.g., genetic mutation), uncontrolled cellular growth, possible invasion into surrounding tissue, and metastasis to other tissues or organs distant from the original body site. Cancerous cells do not possess a growth control mechanism. Lack of cellular differentiation or maturation into specialized, productive cells is another characteristic.
Metastasis refers to the spreading of a cancer from the original site of growth (primary lesion) to a new and remote part of the body (secondary or metastatic lesion).
A benign tumour is a tumour of a uniform size and shape and displays no invasiveness (in terms of infiltrating other tissues) or metastatic properties.
Malignant neoplasms consist of cancer cells that invade (infiltrate) surrounding tissues and metastasize to other tissues and organs.
Tumours are generally classified by tissue of origin: epithelial (carcinoma), connective (sarcoma), lymphatic (lymphoma), and leukocyte (leukemia).

Etiology of Cancer

Causative factors that have been identified include age- and sex-related characteristics, genetic and ethnic factors, oncogenic viruses, environmental and occupational factors, radiation, and immunological factors.

Age- and Gender-Related Differences

The probability that a neoplastic disease will develop generally increases with advancing age.
With the exception of cancers affecting the reproductive system, few cancers exhibit a sex-related difference in incidence.
Few cancers have been confirmed to have a hereditary basis; some types of breast, colon, and stomach cancers are exceptions.
Determination of hormone receptor status and identification of specific gene expression in various types of tumour cells are two advances that help guide therapy tremendously.
Extensive research has indicated that there are cancer-causing (oncogenic) viruses that can affect most mammalian species.
- Epstein-Barr virus is a type of herpesvirus commonly recognized as the cause of infectious mononucleosis. It is also associated with the development of Burkitt lymphoma and nasopharyngeal cancer.
- Infection with human papillomavirus is linked to both cervical and anal cancer.
A mutagen is any substance or physical agent (e.g., radiation) that induces changes in deoxyribonucleic acid (DNA) molecules. Mutations often transform normal cells into cancer cells.

Radiation

Radiation is a well-known and potent carcinogenic agent.
There are two basic types of radiation: (1) ionizing (high energy) and (2) nonionizing (low energy). Both types can be carcinogenic.
Neoplastic cells develop in everyone. However, a healthy person’s immune system recognizes them as abnormal and eliminates them by means of cell-mediated immunity.

Immunological Factors

Neoplastic cells are believed to develop in everyone; however, a healthy person’s immune system recognizes the as abnormal and eliminates them through cell-mediated immunity.
The relationship between cancer and a suppressed immune system has also been noted in cancer patients who are being treated with immunosuppressive drugs after organ transplantation.

Cell Growth Cycle

Normal cells in the body divide (proliferate) in a controlled and organized fashion. A complete cell mitosis cycle from one mitosis to the next is called the generation tie. It is different for all tumours, ranging from hours to days.
The percentage of cells undergoing mitosis at any given time is called the growth fraction of the tumour. The number of cells in the M phase of the cell cycle is called the mitotic index. Chemotherapy is most effective when used in a rapidly dividing or highly proliferative tumours.

Cancer Drug Nomenclature

The more technical term for cancer is malignant neoplasm. Drugs used to treat cancer are therefore known as antineoplastic drugs, but they are also called cancer drugs, anticancer drugs, and, most commonly, cytotoxic chemotherapy or just chemotherapy.
Cancer drugs have a chemical name, a generic name, a trade name, and an investigational or protocol name.
The protocol name is often a code name that consists of a combination of letters and numbers separated by one or more dashes (e.g., STI-571 is the protocol name for imatinib [Gleevec®]).

Drug Therapy

Cancer is normally treated with one or more of three major medical approaches: surgery, radiation therapy, and chemotherapy. The term “chemotherapy” usually refers to the pharmacological treatment of cancer.
Antineoplastic drugs are used to treat malignancies. They may be either cell cycle–specific or cell cycle–nonspecific drugs or may have miscellaneous actions.
Cell cycle–specific drugs kill cancer cells during specific phases of the cell growth cycle. Cell cycle–specific drug classes include antimetabolites, mitotic inhibitors, alkaloid topoisomerase II inhibitors, topoisomerase I inhibitors, and antineoplastic enzymes.
Cell cycle–nonspecific drugs kill cancer cells during any phase of the cell growth cycle.
Several available drugs are classified as cytoprotective and help reduce the toxicity of various antineoplastics.
Regardless of cell cycle characteristics, chemotherapy drugs are more effective on rapidly growing tumours.
Factors that affect the chances of cure and the length of the patient’s survival include the cancer stage at time of diagnosis, the type of cancer and its doubling time, the efficacy of the cancer treatment, the development of drug resistance, and the general health of the patient.
Most cancer drugs have a low therapeutic index, which means that a fine line exists between therapeutic and toxic levels. Clinical experience has shown that a combination of drugs is usually more effective than single-drug therapy. Because drug-resistant cells often develop, exposure to multiple drugs with multiple mechanisms and sites of action will destroy more.
One major drawback to the use of antineoplastic drugs is that nearly all of them cause adverse effects. These toxicities generally stem from the fact that chemotherapy drugs affect rapidly dividing cells—both harmful cancer cells and healthy, normal cells. Three types of rapidly dividing human cells are hair follicle cells, gastrointestinal (GI) cells, and bone marrow cells.
Effects on the GI tract and bone marrow are often dose-limiting adverse effects; that is, the patient can no longer tolerate an increase in dosage that may be necessary to adequately treat the cancer and achieve good disease response.
Targeted drug therapy uses drugs that recognize a specific molecule involved in the growth of cancer cells while mostly sparing healthy cells. One example of such targeted therapy is the newer class of cancer drugs known as monoclonal antibodies.
Relative contraindications for cancer drugs include weakened status of the patient as manifested by indicators such as a very low white blood cell count, an ongoing infectious process, severe compromise in nutritional and hydration status, reduced kidney or liver function, or a decline in organ function in any system that may be further affected by the drug being administered.
In general, most chemotherapy is held when the patient’s absolute neutrophil count is less than 0.05 × 109 (severe neutropenia).
Cancer complicates 1 in 1 000 pregnancies. The choice to use chemotherapy in a pregnant woman is based on risk versus benefit.
More-robust older adult patients are certainly better candidates for cancer treatment, although frail patients often benefit as well, especially in terms of palliative symptom control.

Antimetabolites

Antineoplastic antimetabolites are cell cycle–specific analogues that work by antagonizing the actions of key cellular metabolites.
Antimetabolite antineoplastic drugs are used for the treatment of a variety of solid tumours and some hematological cancers; they may also be used in combination chemotherapy.
Allopurinol and rasburicase are both indicated for the hyperuricemia associated with tumour lysis syndrome and are usually given in anticipation of this condition during various chemotherapy regimens associated with this syndrome.
Antimetabolites can cause hair loss, nausea, vomiting, diarrhea, and myelosuppression.
Metabolic toxicity also includes tumour lysis syndrome, a common postchemotherapy condition often associated with induction chemotherapy for rapidly growing hematological malignancies. It may include hyperphosphatemia, hyperkalemia, and hypocalcemia.
A severe but usually reversible form of dermatological toxicity is known as palmar-plantar dysesthesia or paresthesia. (It is also called “hand–foot syndrome”).
Pemetrexed is a newer folate antagonist with a mechanism of action similar to that of methotrexate. Pralatrexate (Folotyn®) is the newest dihydrofolate reductase inhibitor, specifically indicated for T-cell lymphoma. It is available in Canada through Health Canada’s Special Access Programme.

Mitotic Inhibitors

Mitotic inhibitors include natural products from plants and semisynthetic drugs from plants. Depending on the particular drug, these plant-derived compounds can work in various phases of the cell cycle (late S phase, throughout the G₂ phase, and M phase), but they all work shortly before or during mitosis and thus retard cell division.
Two plant-derived antineoplastic drugs are the taxanes paclitaxel and docetaxel, a semisynthetic taxoid. Docetaxel is pharmacologically similar to paclitaxel.
Mitotic inhibitors are used to treat a variety of solid tumours and some hematological malignancies; they are often used in combination with chemotherapy regimens.
Mitotic inhibitor antineoplastic drugs can cause hair loss, nausea and vomiting, and myelosuppression.
Vincristine and other vinca alkaloids are not given intrathecally. Administering these drugs through the spinal route is almost always fatal, and the death is slow and excruciating.

Alkaloid Topoisomerase II Inhibitors

Etoposide and teniposide are derivatives of epipodophyllotoxin. They exert their cytotoxic effects by inhibiting the enzyme topoisomerase II, which causes breaks in DNA strands. These drugs work during the late S phase and the G₂ phase of the cell cycle.

Topoisomerase I Inhibitors

Topoisomerase I inhibitors are a relatively new class of chemotherapy drugs. The two drugs currently available in this class are topotecan and irinotecan. Both are semisynthetic analogues of the compound camptothecin. The camptothecins inhibit proper DNA function in the S phase by binding to the DNA–topoisomerase I complex.
Topotecan and irinotecan are used primarily to treat ovarian and colorectal cancer.
The main adverse effect of topotecan is bone marrow suppression. Irinotecan’s adverse effects are more severe than those of topotecan. In addition to similar hematological adverse effects, it is associated with severe diarrhea, known as cholinergic diarrhea.

Antineoplastic Enzymes

Two antineoplastic enzymes are commercially available: (1) asparaginase and (2) pegaspargase. They are currently approved exclusively for the treatment of acute lymphocytic leukemia.
Of particular note for the antineoplastic enzymes is the fairly unique adverse effect of impaired pancreatic function. This can lead to hyperglycemia and severe or fatal pancreatitis.

NURSING PROCESS

Assessment

Chemotherapy, or antineoplastic drug therapy, requires very skillful and perceptive nursing care. It is important to act prudently and think critically when making decisions about the nursing care of patients receiving these drugs.
Complete an assessment of cultural, emotional, spiritual, sexual, and financial influences, concerns, and issues.
Perform a pain assessment using objective methods such as an intensity rating scale.
Specific areas of assessment relate to some of the more common adverse effects of chemotherapy on normal, rapidly dividing cells.
One specific assessment consideration associated with the use of the antimetabolite cytarabine is watching for the occurrence of cytarabine syndrome. This usually occurs within 6 to 12 hours after drug administration and is characterized by fever, muscle and bone pain, maculopapular rash, conjunctivitis, and malaise.
In patients receiving mitotic inhibitors (e.g., vinblastine, vincristine) and alkaloid topoisomerase II inhibitors (e.g., etoposide), perform baseline hepatic and renal function tests. Also measure serum uric acid levels, because these levels rise with increased cell death from cancer or its treatment.
Because these drugs have multiple incompatibilities and are irritants (at the intravenous [IV] site and vein) or vesicants (causing cell death with extravasation and necrosis with ulcerations), become familiar with potential solution and drug interactions. Document initial and follow-up assessments of the IV site.
With the use of natural enzyme drugs (e.g., asparaginase, pegaspargase), assess pancreatic function because of the potential for severe or even fatal pancreatitis.
Observe patients for the following characteristics before chemotherapy: (1) genetic markers for oral cancers, (2) genetic determinants of testosterone or estrogen metabolism, and (3) genetically linked enzyme system abnormalities such as those involving specific cytochrome P450 enzymes that metabolically convert nicotine to a carcinogenic substance.

Implementation

For antineoplastic therapy in general, nursing considerations related to reducing fear and anxiety include establishing a therapeutic relationship beginning with trust and empathy.
A variety of interventions may be indicated for the management of stomatitis or excessive oral mucosa dryness and irritation. Instruct the patient to perform oral hygiene before and after eating or as needed to provide cleanliness and comfort. Recommend using a soft-bristle toothbrush or soft-tipped toothette or swab with solutions of diluted warm saline. If dentures are worn, remove and clean them frequently. Advise keeping the lips moist and using sugarless candy or gum to stimulate saliva flow. Stress that spicy, acidic, or hot foods; alcohol; and tobacco must be avoided. Oral antifungal suspensions may be ordered to treat white patches on the oral mucosa.
Educate the patient to enhance comfort during times of nausea and vomiting, including restricting oral intake; removing noxious odours or sights to avoid stimulating the vomiting centre; performing oral hygiene as needed; promoting relaxation through slow, deep breathing and other techniques; consuming small, frequent meals and eating slowly; and consuming clear liquids and a bland diet.

Evaluation

Risk of infection from leukopenia or neutropenia or immunosuppression is one of the more significant adverse effects and requires close attention.
Encourage patients with immune suppression to be aware of environments and persons to avoid, such as individuals who have recently been vaccinated (who may have a subclinical infection) or who have a cold or flu or other symptoms of an infection. Maintain a “low-microbe” diet by washing fresh fruits and vegetables and cooking foods well.
Inform the patient that antineoplastics may also have a negative impact on the reproductive tract, causing destruction of the germinal epithelium of the testes and damage to the ovaries and to a fetus (teratogenesis).
GI adverse effects usually occur on about the fourth day, which may require preplanning for special pharmacological interventions (e.g., antiemetics, antispasmodics, and analgesics) and nonpharmacological measures (dietary changes, oral care).
Therapeutic responses may manifest as clinical improvement, decrease in tumour size, and decrease in metastatic spread.