ANTINEOPLASTIC DRUGS

Antineoplastic agents comprise one aspect of chemotherapy. These drugs act on and kill altered human cells. While their action is intended to target abnormal cells, normal cells are also affected. These drugs can work by affecting cell survival or by boosting the immune system in its efforts to combat the abnormal cells.

Table of Common Drugs and Generic Names

Here is a table of commonly encountered antineoplastics, their generic names, and brand names:

Classification	Generic Name	Brand Name
Alkylating Agents	altretamine	Hexalen
	bendamustine	Treanda
	busulfan	Busulfan, Myleran
	carboplatin	Paraplatin
	carmustine	BiCNU, Gliadel
	chlorambucil	Leukeran
	cisplatin	Platinol-AQ
	cyclophosphamide	Cytoxan, Neostar
	dacarbazine	DTIC-Dome
	ifosfamide	Ifex
	lomustine	CeeNu
	mechlorethamine	Mustargen
	melphalan	Alkeran
	oxaliplatin	Eloxatin
	procarbazine	Matulane
	streptozocin	Zanosar
	temozolomide	Temodar
	thiotepa	Thioplex
Antimetabolites	capecitabine	Xeloda
	cladribine	Leustatin
	clofarabine	Clolar
	cytarabine	DepoCyt, Tarabine PFS
	floxuridine	FUDR
	fludarabine	Fludara
	fluorouracil	Adrucil, Carac, Efudex, Fluoroplex
	gemcitabine	Gemzar
	mercaptopurine	Purinethol
	methotrexate	Rheumatrex, Trexall
	pemetrexed	Alimta
	pentostatin	Nipent
	pralatrexate	Folotyn
	thioguanine	Tabloid
Antineoplastic Antibiotics	bleomycin	Blenoxane
	dactinomycin	Cosmegen
	daunorubicin	DaunoXome
	doxorubicin	Adriamycin, Doxil
	epirubicin	Ellence
	idarubicin	Idamycin
	mitomycin	Mutamycin
	mitoxantrone	Novantrone
	valrubicin	Valstar
Mitotic Inhibitors	cabazitaxel	Jevtana
	docetaxel	Taxotere
	etoposide	Toposar, VePesid
	ixabepilone	Ixempra
	paclitaxel	Abraxane, Onxol Taxol
	teniposide	Vumon
	vincristine	Oncovin, Vincasar
	vinorelbine	Navelbine
Hormones and Hormone Modulators	anastrozole	Arimidex
	bicalutamide	Casodex
	degarelix	Degarelix for Injection
	estramustine	Emcyt
	exemestane	Aromasin
	flutamide	(generic)
	fulvestrant	Faslodex
	goserelin	Zoladex
	histrelin	Vantas
	letrozole	Femara
	leuprolide	Lupron, Eligard
	megestrol	Megace
	mitotane	Lysodren
	nilutamide	Nilandron
	tamoxifen	Soltamox
	toremifene	Fareston
	triptorelin pamoate	Trelstar Depot
Cancer Cell-Specific Agents
§  Protein Tyrosine Kinase Inhibitors	everolimus	Afinitor
	gefitinib	Iressa
	imatinib	Gleevec
	lapatinib	Tykerb
	nilotinib	Tasigna
	pazopanib	Votrient
	sorafenib	Nexavar
	sunitinib	Sutent
	temsirolimus	Torisel
§  Epidermal Growth Factor Inhibitor	erlotinib	Tarceva
§  Proteasome Inhibitor	bortezomib	Velcade
Other antineoplastics	arsenic trioxide	Trisenox
	asparaginase	Elspar
	azacitidine	Vidaza
	bexarotene	Targretin
	decitabine	Dacogen
	hydroxyurea	Hydrea
	irinotecan	Camptosar
	nelarabine	Arranon
	pegaspargase	Oncaspar
	porfimer	Photofrin
	sipuleucel-T	Provenge
	talc powder	Sclerosol
	topotecan	Hycamtin
	tretinoin	Vesanoid
	vorinostat	Zolinza

Disease Spotlight: Cancer

§  Cancer is the second leading cause of death in the United States. Treatment is usually multidisciplinary, prolonged, and often debilitating. It can develop at any age.

§  Proliferation of abnormally-dividing cells starts the pathologic process. Genetic abnormalities are passed along daughter cells, eventually producing a tumor or neoplasm that has characteristics quite different from those of the original tissue.

§  Consequently, original cell characteristics are lost. Anaplasia is the loss of cellular differentiation and organization. Autonomy is the ability to grow without usual homeostatic restrictions that regulate cell growth and control.

§  Uncontrolled growth of neoplastic cells will lead to invasion of healthy tissues in the area and metastasis, or traveling from the place of origin to develop new tumors in other areas of the body.

§  Cancers can be divided into two groups: 1) solid tumors; and 2) hematological malignancies. Solid tumors can further be differentiated into carcinomas, or tumors that originate in epithelial cells, and sarcomas, or tumors that originate in the mesenchyme and are made up of embryonic connective tissue cells.

§  The goal of cancer chemotherapy is to decrease the size of neoplasm so that the human immune system can deal with it.

Alkylating Agents

Description

§  Alkylating agents are non-cell cycle specific antineoplastics drugs. They can affect cells even in the resting phase.

§  These are the agents of choice for slow-growing cancers.

Therapeutic Action

The desired and beneficial action of agents for alkylating agents is:

§  Reacting chemically with portions of RNA, DNA, or other cellular proteins to produce their cytotoxic effects.

§  Alkylating agents are most potent when binding with cellular DNA.

§  The oldest drugs in this class are nitrogen mustards.

Indications

Alkylating agents are indicated for the following medical conditions:

§  Treatment of slow-growing cancers, like lymphomas, leukemias, myelomas, some ovarian, testicular, and breast cancers, and pancreatic cancers. 

Here are some important aspects to remember for indication of antineoplastics in different age groups:

Children

§  Treatment of pediatric cancers follow developed antineoplastic protocols and combination therapy is stressed to eliminate as many of the mutant cells as possible. Checking the dosage for children is crucial because of possible drug toxicity. In addition, the nutritional needs and hydration status of children should be included in the considerations for formulating a care plan.

§  Even under therapy, children must be allowed to explore and learn like any other children. They would need extra support and comfort as body image problems, lack of energy, and risk for infection can isolate them. Lastly, bone marrow activity should be monitored carefully and dose should be adjusted carefully.

Adults

§  Adults are also challenged with changes in body image and activities that come with chemotherapy. It is usual for this age group to fear the diagnosis too. Therefore, establishing a good support system is important.

§  Antineoplastic agents are contraindicated to pregnant and nursing women. Education, support, and referrals to appropriate specialists are important. Women of childbearing age should use barrier contraceptives when these drugs are being taken.

Older adults

§  Older patients are more susceptible to GI and CNS adverse effects of antineoplastic therapy, particularly those with hepatic and renal dysfunctions. Precautions are used accordingly. Protection from infection and injury should be the focus of nurses.

Pharmacokinetics

Here are the characteristic interactions of alkylating agents and the body in terms of absorption, distribution, metabolism, and excretion:

Route	Onset	Peak	Duration
Oral	Varies	1 h	15-20 h
T1/2: 60-90 min Metabolism: liver Excretion: kidney (urine)

Contraindications and Cautions

The following are contraindications and cautions for the use of alkylating agents:

§  Pregnancy and lactation. Severe effects to fetus and neonate.

§  Known allergy to drugs. Caution is exercised to prevent hypersensitivity reactions.

§  Bone marrow suppression. The index for redosing and dosing levels

§  Suppressed renal or hepatic function. Interfere with drug metabolism and excretion.

Adverse Effects

Use of alkylating agents may result to these adverse effects:

§  GI: nausea, vomiting, anorexia, diarrhea, and mucous membrane deterioration, hepatic toxicity

§  GU: renal toxicity, potentially toxic increase in uric acid levels

§  Hematological: bone marrow suppression

§  Alopecia or hair loss

Antimetabolites

Description

§  Antimetabolites are drugs that have chemical structures similar to those of various natural metabolites that are necessary for growth and division of rapidly growing neoplastic cells and normal cells.

Therapeutic Action

The desired and beneficial action of antimetabolites is:

§  Inhibiting 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.

§  Inhibit thymidylate synthase, DNA polymerase, or folic acid reductase, all of which are needed for DNA synthesis.

§  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.

Indications

Antimetabolites are indicated for the following medical conditions:

§  Treatment of various leukemias and some GI and basal cell cancers

§  Use has been somewhat limited because neoplastic cells rapidly develop resistance to these agents. Therefore, they are commonly administered as part of combination therapy.

Pharmacokinetics

Here are the characteristic interactions of antimetabolites and the body in terms of absorption, distribution, metabolism, and excretion:

Route	Onset	Peak	Duration
Oral	Varies	1-4 h	–
IV	Rapid	0.5-2 h	–
T1/2: 2-4 h Metabolism: none Excretion: kidney (urine); unchanged

Contraindications and Cautions

The following are contraindications and cautions for the use of antimetabolites:

§  Known allergy to drug. Prevent hypersensitivity reactions

§  Pregnancy and lactation. Severe effects on the fetus and neonate

§  Bone marrow suppression. Index of redosing and dosing levels

§  Renal and hepatic dysfunction. Interfere with drug metabolism and excretion

§  Known GI ulceration or ulcerative diseases. Can be exacerbated by the effects of the drug

Adverse Effects

Use of antimetabolites may result to these adverse effects:

§  CNS: headache, drowsiness, aphasia, fatigue, malaise, dizziness

§  Respiratory: pulmonary toxicity, interstitial pneumonitis

§  Hematological: bone marrow suppression

§  GI: nausea, vomiting, anorexia, diarrhea, mucous membrane deterioration, hepatic toxicity

§  GU: renal toxicity

§  Leucovorin is an active form of folic acid that is used to rescue normal cells from the adverse effects of methotrexate therapy in the treatment of osteosarcoma.

Antineoplastic Antibiotics

Description

§  This group of drugs is selective for bacterial cells. However, they are also toxic to human cells.

§  They are aimed towards rapidly-multiplying cells.

Therapeutic Action

The desired and beneficial action of antineoplastics antibiotic is:

§  Either breaking up DNA links or preventing DNA synthesis

§  They interfere with cellular DNA synthesis by inserting themselves between base pairs in the DNA chain. This causes a mutant DNA molecule, leading to cell death.

Indications

Antineoplastic antibiotics are indicated for the following medical conditions:

§  Treatment of various types of cancer, particularly those with rapidly-dividing nature.

§  These drugs have potentially adverse effects which limit their usefulness in patients with pre-existing disease and those who are debilitated.

Pharmacokinetics

Here are the characteristic interactions of antineoplastic antibiotics and the body in terms of absorption, distribution, metabolism, and excretion:

Route	Onset	Peak	Duration
IV	Rapid	2 h	24-36 h
T1/2: 12 min, then 3.3 h, then 29.6 h Metabolism: liver Excretion: kidney (urine), liver (bile), colon (feces)

Contraindications and Cautions

The following are contraindications and cautions for the use of antineoplastic antibiotics:

§  Known allergy to drug. Prevent hypersensitivity reactions

§  Pregnancy and lactation. Severe effects on the fetus and neonate

§  Bone marrow suppression. Index of redosing and dosing levels

§  Renal and hepatic dysfunction. Interfere with drug metabolism and excretion

§  Known GI ulceration or ulcerative diseases. Can be exacerbated by the effects of the drug

§  Pulmonary problems. Exacerbated by bleomycin or mitomycin

§  Cardiac problems. Exacerbated by idarubicin or mitoxantrone

Adverse Effects

Use of antineoplastic antibiotics may result to these adverse effects:

§  CNS: headache, drowsiness, aphasia, fatigue, malaise, dizziness

§  Respiratory: pulmonary toxicity, interstitial pneumonitis

§  Hematological: bone marrow suppression

§  GI: nausea, vomiting, anorexia, diarrhea, mucous membrane deterioration, hepatic toxicity

§  GU: renal toxicity

§  Alopecia

Mitotic Inhibitors

Description

§  Drugs that kill cells as the process of mitosis begins.

§  Mitotic inhibitors are cell cycle-specific agents that inhibit DNA synthesis.

Therapeutic Action

The desired and beneficial action of mitotic inhibitors is:

§  Interfering with the ability of the cell to divide by blocking or altering the M phase of the cell cycle.

Indications

Mitotic inhibitors are indicated for the following medical conditions:

§  Treatment of a variety of tumors and leukemias.

Pharmacokinetics

Here are the characteristic interactions of mitotic inhibitors and the body in terms of absorption, distribution, metabolism, and excretion:

Route	Onset	Peak	Duration
IV	Varies	15-30 min	–
T1/2: 5 min, then 2.3 hrs, then 85 hrs Metabolism: liver Excretion: kidney (urine), colon (feces)

Contraindications and Cautions

The following are contraindications and cautions for the use of mitotic inhibitors:

§  Known allergy to drug. Prevent hypersensitivity reactions

§  Pregnancy and lactation. Severe effects on the fetus and neonate

§  Bone marrow suppression. Index of redosing and dosing levels

§  Renal and hepatic dysfunction. Interfere with drug metabolism and excretion

§  Known GI ulceration or ulcerative diseases. Can be exacerbated by the effects of the drug

Adverse Effects

Use of mitotic inhibitors may result to these adverse effects:

§  CNS: headache, drowsiness, aphasia, fatigue, malaise, dizziness

§  Respiratory: pulmonary toxicity, interstitial pneumonitis

§  Hematological: bone marrow suppression

§  GI: nausea, vomiting, anorexia, diarrhea, mucous membrane deterioration, hepatic toxicity

§  GU: renal toxicity

§  Can cause necrosis and cellulitis if extravasation occurs

Hormones and Hormone Modulators

Description

§  Some cancers are sensitive to estrogen stimulation. Estrogen-receptor sites on the tumor react with circulating estrogen, and this reaction stimulates the tumor cells to grow and divide.

§  Hormones and hormone modulators block or interfere with these receptor sites to prevent growth of the cancer and cause cell death.

§  Some hormones are used to block the release of gonadotropic hormones in breast or prostate cancer if the tumors are responsive to gonadotropic hormones. Others may block androgen-receptor sites directly.

Therapeutic Action

The desired and beneficial action of hormones and hormone modulators is:

§  Blocking the stimulation of growing cancer cells that are sensitive to the presence of that hormone.

Indications

Hormones and hormone modulators are indicated for the following medical conditions:

§  Treatment of breast cancer in postmenopausal women or in other women without ovarian function.

§  Treatment of prostatic cancers that are sensitive to hormone manipulation.

Pharmacokinetics

Here are the characteristic interactions of hormones and hormone modulators and the body in terms of absorption, distribution, metabolism, and excretion:

Route	Onset	Peak	Duration
Oral	Varies	4-7 h	–
T1/2: 7-14 days Metabolism: liver Excretion: colon (feces)

Contraindications and Cautions

The following are contraindications and cautions for the use of hormones and hormone modulators:

§  Known allergy to drug. Prevent hypersensitivity reactions

§  Hypercalcemia. Contraindication to the use of toremifene because the drug can increase serum calcium levels.

§  Pregnancy and lactation. Severe effects on the fetus and neonate

§  Bone marrow suppression. Index of redosing and dosing levels

§  Renal and hepatic dysfunction. Interfere with drug metabolism and excretion

§  Known GI ulceration or ulcerative diseases. Can be exacerbated by the effects of the drug

Adverse Effects

Use of hormones and hormone modulators may result to these adverse effects:

§  Menopause-associated effects: hot flashes, vaginal spotting, vaginal dryness, moodiness, and depression

§  Hematological: bone marrow suppression

§  GI: hepatic toxicity

§  GU: renal toxicity

§  Hypercalcemia is encountered as the calcium is pulled out of the bones without estrogen activity to promote calcium deposition.

Cancer Cell-Specific Agents

Description

§  These agents are only specific to cancer cells and spare the healthy cells its devastating effects. Patients do not experience the numerous adverse effects associated with antineoplastic chemotherapy.

§  Three groups of drugs are cancer cell-specific: protein tyrosine kinase inhibitors, epidermal growth factor inhibitor, and proteasome inhibitor.

Therapeutic Action

The desired and beneficial action of cancer cell-specific agents is:

§  Protein tyrosine kinase inhibitors act on specific enzymes that are needed for protein building by specific tumor cells. Blocking of these enzymes inhibits tumor cell growth and division.

§  Epidermal growth factor inhibitors are drugs that act on epidermal growth factor receptors which are found in both normal and cancerous cells but are more abundant on the latter.

§  Proteasome inhibitors are drugs indicated for inhibition of proteasome in human cells, a large protein complex that works to maintain cell homeostasis and protein production.

Indications

Cancer cell-specific agents are indicated for the following medical conditions:

§  Imatinib, the first drug approved protein tyrosine kinase inhibitor, is given orally and is approved to treat chronic myelocytic leukemia (CML). It selectively inhibits the Bcr-Abl tyrosine kinase created by the Philadelphia chromosome abnormality in CML.

§  Bortezomib is used for the treatment of multiple myeloma in patients whose disease had progressed after two standard therapies.

Pharmacokinetics

Here are the characteristic interactions of cancer cell-specific agents and the body in terms of absorption, distribution, metabolism, and excretion:

Route	Onset	Peak	Duration
Oral	Slow	2-4 h	–
T1/2: 18-40 h Metabolism: liver Excretion: colon (feces)

Contraindications and Cautions

The following are contraindications and cautions for the use of cancer cell-specific agents:

§  Pregnancy. All drugs in this class is pregnancy category D.

§  Women of childbearing age. Must be advised to use barrier contraceptives while taking these drugs.

§  Lactation. Can enter breastmilk and use is only justified if benefits outweigh the risks.

§  Hepatic dysfunction. Increased risk of toxicity with imatinib and pazopanib.

§  Risk for prolonged QT intervals (hypokalemia, hypomagnesia, taking drugs that can prolong QT intervals). Contraindicated with nilotinib.

§  Known allergy to the drug. Prevent hypersensitivity reactions.

Adverse Effects

Use of cancer cell-specific agents may result to these adverse effects:

§  Imatinib: GI upset, muscle cramps, heart failure, fluid retention, skin rash. Severe adverse effects of traditional antineoplastic therapy (severe bone marrow depression, alopecia, severe GI effects) do not occur.

§  Gefitinib: potentially severe interstitial lung disease and various eye symptoms

§  Pazopanib: some bone marrow depression, diarrhea, hypertension, and liver impairment, change in hair color

§  Lapatinib: diarrhea, liver impairment, altered heart function

§  Erlotinib and bortezomib: cardiovascular events, pulmonary toxicity

§  Bortezomib: peripheral neuropathy, liver and kidney impairment

Interactions

The following are drug-drug interactions involved in the use of antineoplastic agents:

§  Any drug that has potential for hepatic or renal toxicity

§  Adversely affect drugs metabolized in the liver (e.g. oral anticoagulants)

§  Antineoplastic antibiotics can increase toxicity of drugs that are toxic to the heart and lungs.

§  Echinacea: increased risk of hepatotoxicity with antineoplastics

§  Ginkgo: inhibits blood clotting, which can cause problems after surgery or with bleedingneoplasms

§  Saw palmetto: increase the effects of various estrogen hormones and hormone modulators; advise patients taking such drugs to avoid this herb

§  St. John’s wort: can greatly increase photosensitivity, which can cause problems in patient who have received radiation therapy or are taking drugs that cause other dermatological effects. In addition, it can decrease the effectiveness of some antineoplastic agents.

Nursing Considerations

Here are important nursing considerations when administering antineoplastic agents:

Nursing Assessment

These are the important things the nurse should include in conducting assessment, history taking, and examination:

§  Assess for the mentioned cautions and contraindications (e.g. drug allergies, hepatorenal impairment, bone marrow suppression, pregnancy and lactation, etc.) to prevent any untoward complications.

§  Perform a thorough physical assessment (other medications taken, orientation and reflexes, vital signs, bowel sounds, etc.) to establish baseline data before drug therapy begins, to determine effectiveness of therapy, and to evaluate for occurrence of any adverse effects associated with drug therapy.

§  Monitor result of laboratory tests such as CBC with differential to identify possible bone marrow suppression and toxic drug effects and establish appropriate dosing for the drug; and liver and renal function tests to determine need for possible dose adjustment and identify toxic drug effects.

Nursing Diagnoses

Here are some of the nursing diagnoses that can be formulated in the use of these drugs for therapy:

§  Acute pain related to GI, CNS, and skin effects of the drug

§  Disturbed body image related to alopecia, skin effects, and impaired fertility

§  Anxiety related to diagnosis

§  Risk for infection related to bone marrow suppression

Implementation with Rationale

These are vital nursing interventions done in patients who are taking alkylating agents:

§  Arrange for blood tests before, periodically during, and for at least 3 weeks after therapy to monitor bone marrow function to aid in determining the need for a change in dose or discontinuation of the drug.

§  Administer medication according to scheduled protocol and in combination with other drugs as indicated to improve effectiveness.

§  Ensure that patient is well hydrated to decrease risk of renal toxicity.

§  Protect the patient from infection; limit invasive procedures when bone marrow suppression limits the patient’s immune/inflammatory responses.

§  Provide small, frequent meals, frequent mouth care, and dietary consultation as appropriate to maintain nutrition when GI effects are severe.

§  Arrange for proper head covering at extremes of temperature if alopecia occurs; a wig, scarf, or hat is important for maintaining body temperature.

§  Plan for rest periods because fatigue and weakness are common effects of the drug.

Evaluation

Here are aspects of care that should be evaluated to determine effectiveness of drug therapy:

§  Monitor patient response to therapy (alleviation of cancer being treated, palliation of signs and symptoms of cancer).

§  Monitor for adverse effects (bone marrow suppression, GI toxicity, neurotoxicity, and alopecia, renal or hepatic dysfunction).

§  Evaluate patient understanding on drug therapy by asking patient to name the drug, its indication, and adverse effects to watch for.

§  Monitor patient compliance to drug therapy.

Posted in: Pharmacology