CYTOTOXIC/ ANTINEOPLASTIC DRUGS
Antineoplastic drugs alter human cells in a variety of ways. Their action is intended to target the
abnormal cells that compose the neoplasm or cancer, having a greater impact on them than on
normal cells.
Unfortunately, normal cells also are affected by antineoplastic agents.
CANCER
Cancer is a disease that can strike a person at any age. It remains second only to coronary
disease as the leading cause of death in the United States. Treatment of cancer can be
prolonged and often debilitating. The patient can experience numerous and wide-ranging
complications and effects.
All cancers start with a single cell that is genetically different from the other cells in the
surrounding tissue. This cell divides, passing along its abnormalities to daughter cells, eventually
producing a tumor or neoplasm that has characteristics quite different from those of the
original tissue.
As the abnormal cells continue to divide, they lose more and more of their original cell
characteristics. The cancerous cells exhibit anaplasia—a loss of cellular differentiation and
organization, which leads to a loss of their ability to function normally. They also exhibit
autonomy, growing without the usual homeostatic restrictions that regulate cell growth and
control. This loss of control allows the cells to form a tumor.
Over time, these neoplastic cells grow uncontrollably, invading and damaging healthy tissue in
the area and even undergoing metastasis, or traveling from the place of origin to develop new
tumors in other areas of the body where conditions are favorable for cell growth.
The abnormal cells release enzymes that generate blood vessels (angiogenesis) in the area to
supply both oxygen and nutrients to the cells, thus contributing to their growth. Overall, the
cancerous cells rob the host cells of energy and nutrients and block normal lymph and vascular
vessels as the result of pressure and intrusion on normal cells, leading to a loss of normal
cellular function.
The body’s immune system can damage or destroy some neoplastic cells. T cells, which
recognize the abnormal cells and destroy them; antibodies, which form in response to parts of
the abnormal cell protein; interferons; and tissue necrosis factor all play a role in the body’s
attempt to eliminate the abnormal cells before they become uncontrollable and threaten the
life of the host. Once the neoplasm has grown and enlarged, it may overwhelm the immune
system, which is no longer able to manage the problem.
Causes of Cancer
What causes the cells to mutate and become genetically different is not clearly understood. In
some cases, a genetic predisposition to such a mutation can be found. Breast cancer, for
example, seems to have a definite genetic link.
In other cases, viral infection, constant irritation and cell turnover, and even stress have been
blamed for the ensuing cancer. Stress reactions suppress the activities of the immune system ,
so if a cell is mutating while a person is under prolonged stress, research suggests that the cell
has a better chance of growing into a neoplasm than when the person’s immune system is fully
active. Pipe smokers are at increased risk for development of tongue and mouth cancers
because the heat of the pipe and chemicals in the pipe tobaccos and smoke continuously
destroy normal cells, which must be replaced rapidly, increasing the chances for development
of a mutant cell. People living in areas with carcinogenic or cancer-causing chemicals in the air,
water, or even the ground are at increased risk of developing mutant cells
Antineoplastic drugs can work by affecting cell survival or by boosting the immune system in its
efforts to combat the abnormal cells
Classification
1. alkylating agents
2. antimetabolites
3. antineoplastic antibiotics
4. mitotic inhibitors
5. hormones and hormone modulators,
6. cancer cell–specific agents
7. protein tyrosine
The goal of cancer therapy, much like that of antiinfective therapy, is to limit the offending cells
to the degree that the immune system can then respond without causing too much toxicity to
the host.
However, this is a particularly difficult task when using antineoplastic drugs because, for the
most part, these agents are not specific to mutant cells, and affect normal human cells as well.
Antineoplastic drugs are associated with many adverse effects, with specific adverse effects
occurring with particular drugs. These effects are often unpleasant and debilitating. Some
antineoplastic drugs exert toxic effects on ova and sperm production, affecting the person’s
fertility. These agents are also usually selective for rapidly growing cells, posing a danger to the
developing.
ALKYLATING AGENTS
Because alkylating agents can affect cells even in the resting phase, these drugs are said to be
non–cell cycle specific. They are most useful in the treatment of slow-growing cancers, which
have many cells in the resting phase.
Alkylating agents examples
busulfan
carboplatin
carmustine
chlorambucil
cisplatin
cyclophosphamide
Therapeutic Actions and Indications
Alkylating agents produce their cytotoxic effects by reacting chemically with portions of the
RNA, DNA, or other cellular proteins, being most potent when they bind with cellular DNA.
These drugs are most useful in the treatment of slow-growing cancers such as various
lymphomas, leukemias, myelomas, some ovarian, testicular, and breast and some pancreatic
cancers.
Contraindications and Cautions
Alkylating agents are contraindicated during pregnancy and lactation due to their potential for
severe effects on the fetus and neonate.
Caution is necessary when giving alkylating agents to any individual with a known allergy to any
of them; with bone marrow suppression, which is often the index for redosing and dosing levels;
or with suppressed renal or hepatic function, which may interfere with metabolism or excretion
of these drugs and often indicates a need to change the dose.
Hematological effects include bone marrow suppression, with leukopenia, thrombocytopenia,
anemia, and pancytopenia, secondary to the effects of the drugs on the rapidly multiplying cells
of the bone marrow.
Adverse Effects
GI effects include nausea, vomiting, anorexia, diarrhea, and mucous membrane deterioration,
all of which are related to the drugs’ effects on the rapidly multiplying cells of the GI tract.
Hepatic toxicity and renal toxicity may occur, depending on the exact mechanism of action.
Alopecia, or hair loss, related to effects on the hair follicles, may also occur. All drugs that cause
cell death can cause a potentially toxic increase in uric acid levels.
Allopurinol has been used to help alleviate this problem and in 2004, a new drug, rasburicase,
was introduced to manage uric acid levels in pediatric patients
Dosage
Busulfan (Busulfex, Myleran)
Induction: 4–8 mg/d PO
Maintenance: 1–3 mg/d PO
Injection: 0.8 mg/kg as a 2-h IV infusion q6h for 4 d via a central venous catheter
Treatment of chronic myelogenous leukemia; not effective in blastic phase or without the
Philadelphia chromosome
Special considerations: dosing monitored by effects on bone marrow; always push fluids to
decrease toxic renal effects; alopecia is common
Cisplatin (Platinol-AQ) 20–50 mg/m2/d IV, once every 3 wk used in combination with other
antineoplastic agents Combination therapy for metastatic testicular or ovarian tumors,
advanced bladder cancers
Special considerations: neurotoxic, nephrotoxic, and can cause serious hypersensitivity
reactions
cyclophosphamide (Cytoxan, Neosar) Induction: 40–50 mg/kg/d IV over
2–5 d, or 1–5 mg/kg/d PO
Maintenance: 1–5 mg/kg/d PO, or
10–15 mg/kg IV q7–10d Treatment of lymphoma, myelomas, leukemias, and other cancers
in combination with other drugs
Special considerations: hemorrhagic cystitis is a potentially fatal side effect; alopecia is
common
NURSING CONSIDERATIONS
Evaluation
■ Monitor patient response to the drug (alleviation of cancer being treated, palliation of signs
and symptoms of cancer).
■ Monitor for adverse effects (bone marrow suppression, GI toxicity, neurotoxicity, alopecia,
renal or hepatic dysfunction).
■ Evaluate the effectiveness of the teaching plan (patient can name the drug, dosage, possible
adverse effects to watch for, and specific measures to help avoid adverse effects).
■ Administer medication according to scheduled protocol and in combination with other drugs
as indicated to improve effectiveness.
■ Ensure that the patient is well hydrated to decrease risk of renal toxicity.
■ Protect the patient from exposure to infection; limit invasive procedures when bone marrow
suppression limits the patient’s immune/infl ammatory responses.
■ Provide small, frequent meals, frequent mouth care,and dietary consultation as appropriate
to maintain nutrition when GI effects are severe. Anticipate the need for antiemetics if
necessary
■ Arrange for proper head covering at extremes of temperature if alopecia occurs; a wig, scarf,
or hat is important for maintaining body temperature. If alopecia is an anticipated effect of drug
therapy, advise the patient to obtain a wig or head covering before the condition occurs to
promote self-esteem and a positive body image.
ANTIMETABOLITES
Antimetabolites are drugs that have chemical structures similar to those of various natural
metabolites that are necessary for the growth and division of rapidly growing neoplastic cells
and normal cells.
Antimetabolites include
capecitabine (Xeloda)
cytarabine
floxuridine
fluorouracil
gemcitabine
Mercaptopurine
methotrexate
Therapeutic Actions and Indications
Antimetabolites inhibit DNA production in cells that depend on certain natural metabolites to
produce their DNA. They replace these needed metabolites and thereby prevent normal
cellular function.
They are considered to be S phase specific in the cell cycle. They are most effective in rapidly
dividing cells, preventing cell replication, and leading to cell death
The antimetabolites are indicated for the treatment of various leukemias and some GI and
basal cell cancers.
Use of these drugs has been somewhat limited because neoplastic cells rapidly develop
resistance to these agents. For this reason, these drugs are usually administered as part of a
combination therapy.
Contraindications and Cautions
Antimetabolites are contraindicated for use during pregnancy and lactation because of the
potential for severe effects on the fetus and neonate.
Caution is necessary when administering antimetabolites to any individual with a known allergy
to any of them to prevent hypersensitivity reactions; with bone marrow suppression, which is
often the index for redosing and dosing levels.
Caution is needed in renal or hepatic dysfunction, which might interfere with the metabolism or
excretion of these drugs and often indicates a need to change the dose; and with known
GI ulcerations or ulcerative diseases that might be exacerbated by the effects of these drugs.
Adverse Effect
Hematological effects include bone marrow suppression, with leukopenia, thrombocytopenia,
anemia, and pancytopenia, secondary to the effects of the drugs on the rapidly multiplying
cells. Toxic GI effects include nausea, vomiting, anorexia, diarrhea, and mucous membrane
deterioration, all of which are related to drug effects on the rapidly multiplying cells of the GI
tract. CNS effects include headache, drowsiness, aphasia, fatigue, malaise, and dizziness.
Dosage
Methotrexate
Dose varies with route and disease being treated; 15–30 mg PO or intramuscularly (IM) is
common
Treatment of leukemias, psoriasis, rheumatoid arthritis, and choriocarcinomas
Special considerations: hypersensitivity reactions can be severe; liver toxicity and GI
complications are common; monitor for bone marrow suppression and increased susceptibility
to infections; dose pack available for the oral treatment of psoriasis and rheumatoidarthritis
Fluorouracil
12 mg/kg/d IV on days 1–4, then 6 mg/kg IV on days 6, 8, 10, and 12
Palliative treatment of various GI cancers; topical treatment of basal cell carcinoma and actinic
and solar keratoses
Special considerations: GI toxicity, bone marrow suppression, alopecia, and skin rash are
common; avoid occlusive dressings with topical forms; wash hands thoroughly after coming in
contact with drug
Nursing diagnoses related to drug therapy might include
■ Acute Pain related to GI, CNS, or skin effects of the drug
■ Disturbed Body Image related to alopecia, skin effects, impaired fertility
■ Fear, Anxiety related to diagnosis and treatment
■ Imbalanced Nutrition, less than body requirements
■ Risk for Infection
■ Deficient Knowledge regarding drug therapy
■ Arrange for blood tests to monitor bone marrow function before, periodically during, and for
at least 3 weeks after therapy to arrange to discontinue the drug or reduce the dose as needed
■ Administer medication according to the scheduled protocol and in combination with other
drugs as indicated to improve the effectiveness of drug therapy.
■ Ensure that the patient is well hydrated to decrease the risk of renal toxicity.
■ Provide small, frequent meals, frequent mouth care, and dietary consultation as appropriate
to maintain nutrition when GI effects are severe. Anticipate the use of antiemetics as necessary.
■ Arrange for proper head covering at extremes of temperature if alopecia occurs; a wig, scarf,
or hat is important for maintaining body temperature. If alopecia is an anticipated effect of drug
therapy, advise the patient to obtain a wig or head covering before the condition occurs to
promote self-esteem and a positive body image.
■ Protect the patient from exposure to infections because bone marrow suppression will limit
immune/inflammatory responses.
■ Provide support and encouragement to help the patient cope with the diagnosis and the
effects of drug therapy.
