Antineoplastic Agents: Nursing Pharmacology Study Guide for Nurses

Antineoplastic Agents: Generic and Brand Names

• 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 (Emyct)
  • exemestane (Aromasin)
  • flutamide
  • 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 Inhibitors
    • 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, behind heart disease (CDC), and treatment is usually multidisciplinary, prolonged, and debilitating. It can develop at any age. The process starts when abnormally dividing cells proliferate and pass genetic abnormalities to daughter cells, eventually forming a tumor or neoplasm with characteristics unlike the original tissue. Anaplasia is the loss of cellular differentiation and organization; autonomy is the ability to grow without the homeostatic restrictions that normally regulate cell growth. Uncontrolled growth invades nearby healthy tissue, and metastasis is the spread from the original site to form new tumors elsewhere.

Cancers split into two groups: solid tumors and hematological malignancies. Solid tumors divide further into carcinomas (originating in epithelial cells) and sarcomas (originating in the mesenchyme, made of embryonic connective tissue cells). The goal of chemotherapy is to shrink the neoplasm enough for the immune system to handle it.

Alkylating Agents

Alkylating agents are non-cell-cycle-specific. They hit cells even in the resting phase, which makes them the agents of choice for slow-growing cancers.

Therapeutic Action

They react chemically with portions of RNA, DNA, or other cellular proteins to produce cytotoxic effects, and they are most potent when bound to cellular DNA. The oldest drugs in the class are the nitrogen mustards.

Indications

Slow-growing cancers: lymphomas, leukemias, myelomas, some ovarian, testicular, and breast cancers, and pancreatic cancers.

Age-group points that apply across antineoplastics:

• Children. Treatment follows established protocols, and combination therapy is stressed to wipe out as many mutant cells as possible. Check dosing carefully because of toxicity risk, and build nutrition and hydration into the care plan. Let children keep exploring and learning; they need extra support and comfort, since body-image problems, low energy, and infection risk can isolate them. Monitor bone marrow activity closely and adjust the dose accordingly.
• Adults. They face body-image and activity changes and often fear the diagnosis, so a strong support system matters. Antineoplastics are contraindicated in pregnancy and lactation; provide education, support, and referrals. Women of childbearing age should use barrier contraceptives while on these drugs.
• Older adults. More susceptible to GI and CNS adverse effects, especially with hepatic and renal dysfunction. Focus on protection from infection and injury.

Contraindications and Cautions

• Pregnancy and lactation. Severe effects on the fetus and neonate.
• Known allergy. Prevents hypersensitivity reactions.
• Bone marrow suppression. Sets the index for redosing and dose levels.
• Suppressed renal or hepatic function. Interferes with metabolism and excretion.

Adverse Effects

• GI: nausea, vomiting, anorexia, diarrhea, mucous membrane deterioration, hepatic toxicity
• GU: renal toxicity, potentially toxic rise in uric acid
• Hematological: bone marrow suppression
• Alopecia

Antimetabolites

Antimetabolites have chemical structures similar to the natural metabolites that rapidly growing neoplastic and normal cells need to grow and divide.

Therapeutic Action

They inhibit DNA production in cells that depend on certain natural metabolites, replacing those metabolites and blocking normal cell function. They inhibit thymidylate synthase, DNA polymerase, or folic acid reductase, all needed for DNA synthesis. Being S-phase specific, they are most effective in rapidly dividing cells, preventing replication and causing cell death.

Indications

Various leukemias and some GI and basal cell cancers. Use is somewhat limited because neoplastic cells rapidly develop resistance, so they are usually given as part of combination therapy.

Contraindications and Cautions

• Known allergy. Prevents hypersensitivity reactions.
• Pregnancy and lactation. Severe effects on the fetus and neonate.
• Bone marrow suppression. Index for redosing and dose levels.
• Renal and hepatic dysfunction. Interferes with metabolism and excretion.
• Known GI ulceration or ulcerative disease. Worsened by drug effects.

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 used to rescue normal cells from the adverse effects of methotrexate therapy in osteosarcoma treatment.

Antineoplastic Antibiotics

This group is selective for bacterial cells but also toxic to human cells, and it targets rapidly multiplying cells.

Therapeutic Action

They either break up DNA links or prevent DNA synthesis. By inserting between base pairs in the DNA chain, they create a mutant DNA molecule that leads to cell death.

Indications

Various cancers, especially rapidly dividing ones. Their adverse effects limit their usefulness in patients with pre-existing disease or who are debilitated.

Contraindications and Cautions

• Known allergy. Prevents hypersensitivity reactions.
• Pregnancy and lactation. Severe effects on the fetus and neonate.
• Bone marrow suppression. Index for redosing and dose levels.
• Renal and hepatic dysfunction. Interferes with metabolism and excretion.
• Known GI ulceration or ulcerative disease. Worsened by drug effects.
• Pulmonary problems. Worsened by bleomycin or mitomycin.
• Cardiac problems. Worsened by idarubicin or mitoxantrone.

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

Mitotic inhibitors kill cells as mitosis begins. They are cell-cycle-specific agents that inhibit DNA synthesis.

Therapeutic Action

They interfere with cell division by blocking or altering the M phase of the cell cycle.

Indications

A variety of tumors and leukemias.

Contraindications and Cautions

• Known allergy. Prevents hypersensitivity reactions.
• Pregnancy and lactation. Severe effects on the fetus and neonate.
• Bone marrow suppression. Index for redosing and dose levels.
• Renal and hepatic dysfunction. Interferes with metabolism and excretion.
• Known GI ulceration or ulcerative disease. Worsened by drug effects.

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
• Necrosis and cellulitis if extravasation occurs

Hormones and Hormone Modulators

Some cancers are sensitive to estrogen stimulation: estrogen-receptor sites on the tumor react with circulating estrogen, driving the tumor cells to grow and divide. Hormones and hormone modulators block or interfere with these receptor sites to stop growth and cause cell death. Some block the release of gonadotropic hormones in responsive breast or prostate cancer; others block androgen-receptor sites directly.

Therapeutic Action

They block the stimulation of cancer cells that are sensitive to a given hormone.

Indications

• Breast cancer in postmenopausal women or other women without ovarian function.
• Prostate cancers sensitive to hormone manipulation.

Contraindications and Cautions

• Known allergy. Prevents hypersensitivity reactions.
• Hypercalcemia. Contraindicates toremifene, which can raise serum calcium.
• Pregnancy and lactation. Severe effects on the fetus and neonate.
• Bone marrow suppression. Index for redosing and dose levels.
• Renal and hepatic dysfunction. Interferes with metabolism and excretion.
• Known GI ulceration or ulcerative disease. Worsened by drug effects.

Adverse Effects

• Menopause-associated: hot flashes, vaginal spotting, vaginal dryness, moodiness, depression
• Hematological: bone marrow suppression
• GI: hepatic toxicity
• GU: renal toxicity
• Hypercalcemia, as calcium pulls out of the bones without estrogen activity to promote calcium deposition

Cancer Cell-Specific Agents

These agents target cancer cells and spare healthy ones, so patients avoid most of the adverse effects of traditional chemotherapy. Three groups: protein tyrosine kinase inhibitors, epidermal growth factor inhibitor, and proteasome inhibitor.

Therapeutic Action

• Protein tyrosine kinase inhibitors act on specific enzymes that certain tumor cells need to build protein. Blocking those enzymes halts tumor cell growth and division.
• Epidermal growth factor inhibitors act on EGF receptors, found on both normal and cancerous cells but more abundant on cancer cells.
• Proteasome inhibitors inhibit the proteasome, a large protein complex that maintains cell homeostasis and protein production.

Indications

• Imatinib, the first protein tyrosine kinase inhibitor approved by the FDA (in 2001), is given orally for chronic myelocytic leukemia (CML). It selectively inhibits the Bcr-Abl tyrosine kinase created by the Philadelphia chromosome abnormality in CML, and it reshaped CML from a frequently fatal disease into one most patients now live with long-term (National Cancer Institute).
• Bortezomib treats multiple myeloma in patients whose disease has progressed after two standard therapies.

Contraindications and Cautions

• Pregnancy. Every drug in this class is pregnancy category D.
• Women of childbearing age. Must use barrier contraceptives while taking these drugs.
• Lactation. Enters breast milk; use only when benefits outweigh the risks.
• Hepatic dysfunction. Increased toxicity risk with imatinib and pazopanib.
• Risk for prolonged QT interval (hypokalemia, hypomagnesemia, or other QT-prolonging drugs). Contraindicates nilotinib.
• Known allergy. Prevents hypersensitivity reactions.

Adverse Effects

• Imatinib: GI upset, muscle cramps, heart failure, fluid retention, skin rash. The severe effects of traditional 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, liver impairment, hair color change.
• Lapatinib: diarrhea, liver impairment, altered heart function.
• Erlotinib and bortezomib: cardiovascular events, pulmonary toxicity.
• Bortezomib: peripheral neuropathy, liver and kidney impairment.

Interactions

• Any drug with potential for hepatic or renal toxicity.
• Drugs metabolized in the liver are adversely affected (for example, oral anticoagulants).
• Antineoplastic antibiotics can increase the toxicity of drugs toxic to the heart and lungs.
• Echinacea: increased hepatotoxicity risk with antineoplastics.
• Ginkgo: inhibits blood clotting, a problem after surgery or with bleeding neoplasms.
• Saw palmetto: increases the effects of estrogen hormones and hormone modulators; have patients on those drugs avoid this herb.
• St. John's wort: greatly increases photosensitivity, a problem after radiation therapy or with other photosensitizing drugs, and can reduce the effectiveness of some antineoplastics.

Pharmacokinetics

Alkylating Agents

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

Antimetabolites

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

Antineoplastic Antibiotics

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

Mitotic Inhibitors

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

Hormones and Hormone Modulators

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

Cancer Cell-Specific Agents

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

Nursing Considerations

Assessment. Screen for cautions and contraindications (drug allergies, hepatorenal impairment, bone marrow suppression, pregnancy and lactation). Do a full physical (other medications, orientation and reflexes, vital signs, bowel sounds) for baseline data. Monitor labs: CBC with differential for bone marrow suppression and toxic effects and to set dosing, plus liver and renal function tests for dose adjustment and toxicity.

Nursing diagnoses. Acute pain related to GI, CNS, and skin effects; disturbed body image related to alopecia, skin effects, and impaired fertility; anxiety related to diagnosis; risk for infection related to bone marrow suppression.

Interventions. Draw blood tests before, periodically during, and for at least 3 weeks after therapy to track bone marrow function and guide dose changes or discontinuation. Give medication per the scheduled protocol and in combination as indicated. Keep the patient well hydrated to lower renal toxicity risk. Protect the patient from infection and limit invasive procedures when bone marrow suppression blunts immune and inflammatory responses. Offer small, frequent meals, frequent mouth care, and dietary consultation for severe GI effects. Arrange proper head covering in temperature extremes when alopecia occurs, since a wig, scarf, or hat helps maintain body temperature. Plan rest periods, since fatigue and weakness are common.

Evaluation. Monitor response (alleviation of the cancer, palliation of signs and symptoms) and adverse effects (bone marrow suppression, GI toxicity, neurotoxicity, alopecia, renal or hepatic dysfunction). Confirm the patient can name the drug, its indication, and adverse effects, and check compliance.

Frequently Asked Questions

Why do antineoplastic drugs cause so many side effects?

Most antineoplastics kill cells that divide rapidly, and they cannot fully tell cancer cells from healthy ones that also divide fast: bone marrow, GI lining, and hair follicles. That overlap is why bone marrow suppression, nausea and mouth sores, and alopecia show up across nearly every class.

What is the most dangerous toxicity nurses monitor for?

Bone marrow suppression is the central concern, because it lowers white cells, red cells, and platelets, raising the risk of infection, anemia, and bleeding. Blood counts are drawn before, during, and for at least three weeks after therapy to guide dosing, and the patient is protected from infection and invasive procedures during the nadir.

What is leucovorin rescue?

Leucovorin is an active form of folic acid given to "rescue" normal cells from high-dose methotrexate, an antimetabolite used in cancers such as osteosarcoma. It lets healthy cells recover while the methotrexate keeps acting on tumor cells.

How are cell-cycle-specific and non-cell-cycle-specific drugs different?

Cell-cycle-specific agents (antimetabolites, mitotic inhibitors) act during a particular phase of division, so they hit fast-growing tumors hardest. Non-cell-cycle-specific agents (alkylating agents) damage cells even at rest, which makes them useful against slower-growing cancers.

How do targeted agents like imatinib differ from traditional chemotherapy?

Targeted agents act on specific molecules cancer cells depend on, such as the Bcr-Abl tyrosine kinase in CML, so they largely spare healthy tissue and avoid the severe bone marrow suppression, alopecia, and GI toxicity of traditional chemotherapy. Imatinib, the first FDA-approved tyrosine kinase inhibitor (2001), is the classic example (National Cancer Institute).

Why must patients of childbearing potential use contraception on these drugs?

Antineoplastics are contraindicated in pregnancy and lactation because they cause severe harm to a fetus or neonate. Patients who can become pregnant should use reliable barrier contraception while on therapy, and the team should provide education, support, and referrals.