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Chapter 46
Antineoplastic Drugs Part 2: Cell Cycle
– Nonspecific Drugs and
Miscellaneous Drugs
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
Cancer Drugs:
Antineoplastic Medications

Cell cycle–nonspecific (CCNS) antineoplastic
drugs


Alkylating drugs
Cytotoxic antibiotics
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
2
Alkylating Drugs



Classic alkylators (nitrogen mustards)
Nitrosoureas
Miscellaneous alkylators
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
3
Alkylating Drugs: Mechanism of
Action



Work by preventing cancer cells from
reproducing
Alter the chemical structure of the cells’
deoxyribonucleic acid (DNA)
Bifunctional or polyfunctional
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
4
Organization of DNA and Site of
Action of Alkylating Drugs
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
5
Alkylating Drugs: Indications

Used in combination with other drugs to treat
various types of cancer, such as:

Recurrent ovarian cancer
 Brain tumors
 Lymphomas
 Leukemias
 Breast cancer
 Bladder cancer
 Others
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
6
Alkylating Drugs: Adverse Effects

Dose-limiting adverse effects



Alopecia
Nephrotoxicity, peripheral neuropathy, ototoxicity


Nausea and vomiting, myelosuppression
Hydration can prevent nephrotoxicity
Extravasation causes tissue damage and
necrosis
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
7
Alkylating Drugs: Examples





cisplatin (Platinol)
cyclophosphamide (Cytoxan)
mechlorethamine (Mustine, nitrogen mustard)
carmustine (BiCNU)
Others
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
8
Cytotoxic Antibiotics



Natural substances produced by the mold
Streptomyces
Synthetic substances also used
Used to treat cancer; too toxic to treat infections
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
9
Cytotoxic Antibiotics (cont’d)

Anthracycline antibiotics


daunorubicin, doxorubicin, epirubicin, idarubicin,
valrubicin
Other cytotoxic antibiotics

bleomycin, dactinomycin, mitomycin, mitoxantrone,
plicamycin
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
10
Cytotoxic Antibiotics: Mechanism of
Action


CCNS drugs are active in all phases of the cell
cycle
Act by intercalation, resulting in blockade of DNA
synthesis
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
11
Cytotoxic Antibiotics: Indications


Used in combination chemotherapy regimens
Used to treat a variety of solid tumors and some
hematologic malignancies

Leukemia, ovarian, breast, bone, others
 Squamous cell carcinomas
 AIDS-related Kaposi’s sarcoma (when intolerant to
other treatments)
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
12
Cytotoxic Antibiotics:
Adverse Effects




All can produce bone marrow suppression,
except bleomycin
Hair loss, nausea and vomiting,
myelosuppression
Heart failure (daunorubicin)
Acute left ventricular failure (doxorubicin)
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
13
Cytotoxic Antibiotics:
Adverse Effects (cont’d)



Pulmonary fibrosis and pneumonitis (bleomycin)
Liver, kidney, and cardiovascular toxicities
Many others
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
14
Cytotoxic Antibiotics:
Adverse Effects (cont’d)

Cardiomyopathy is associated with large
amounts of doxorubicin

Routine monitoring of cardiac ejection fraction with
multiple-gated acquisition (MUGA) scans
 Cumulative dose limitations
 Cytoprotective drugs such as dexrazoxane can
decrease the incidence of this devastating toxicity
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
15
Classroom Response Question
Which cytotoxic antibiotic does the nurse identify
as most likely to cause pulmonary fibrosis?
A. plicamycin
B. mitoxantrone
C. mitomycin
D. bleomycin
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
16
Miscellaneous Antineoplastics

bevacizumab (Avastin)




Angiogenesis inhibitor
Blocks blood supply to the growing tumor
Used to treat metastatic colon cancer, rectal cancer in
combination with 5-fluorouracil, non–small cell lung
cancer, and malignant glioblastoma
Many adverse effects, including nephrotoxicity
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
17
Classroom Response Question
Bevacizumab (Avastin) is an angiogenesis inhibitor. Which
statement correctly describes the mechanism of action of
an angiogenesis inhibitor?
A. It inhibits the formation of blood cells.
B. It inhibits the creation of new blood vessels in the tumor
mass.
C. It interferes with the synthesis of DNA in the cancer
tumor.
D. It causes cell death by inhibiting enzymes.
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
18
Miscellaneous Antineoplastics
(cont’d)

hydroxyurea (Hydrea, Droxia)

Action similar to antimetabolites
 Used to treat squamous cell carcinoma and some
leukemias
 Many adverse effects (e.g., edema, drowsiness,
headache, rash, hyperuricemia, nausea, vomiting,
dysuria, myelosuppression, nephrotoxicity, pulmonary
fibrosis)
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
19
Miscellaneous Antineoplastics
(cont’d)

imatinib (Gleevec)





Used to treat chronic myeloid leukemia (CML)
Targeted therapy, but it is NOT a monoclonal antibody
Works by inhibiting an enzyme that is active in the
CML process
Use with other hepatic-metabolized drugs may cause
severe interactions
Many adverse effects and drug interactions
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
20
Miscellaneous Antineoplastics
(cont’d)

mitotane (Lysodren)

Adrenal cytotoxic drug
 Used specifically for inoperable adrenal corticoid
carcinoma
 Oral form only
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
21
Hormonal Drugs


Used to treat a variety of neoplasms in men and
women
Hormonal therapy used to

Oppose effects of hormones
 Block the body’s sex hormone receptors

Used most commonly as adjuvant and palliative
therapy

But may be a drug of first choice for some cancers
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
22
Hormonal Drugs for FemaleSpecific Neoplasms

Aromatase inhibitors


Selective estrogen receptor modulators


megestrol (Megace), medroxyprogesterone
Androgens


tamoxifen, toremifene
Progestins


anastrozole, aminoglutethimide
fluoxymesterone, testolactone
Estrogen receptor antagonist

fulvestrant
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
23
Hormonal Drugs for Male-Specific
Neoplasms

Antiandrogens


Gonadotropin-releasing hormone antagonists


bicalutamide, flutamide, nilutamide
leuprolide, goserelin
Antineoplastic hormone

estramustine
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
24
Radiopharmaceuticals
and Antineoplastics

Porfimer sodium


Used to treat esophageal and bronchial tumors in
combination with laser light therapy
Radiopharmaceuticals


Used to treat a variety of cancers, or symptoms
caused by cancers
Administered by nuclear medicine specialists
• samarium SM 153 lexidronam
• sodium iodide I 131
• sodium phosphate P 32
• Others
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
25
Extravasation



Leaking of an antineoplastic drug into
surrounding tissues during IV administration
Can result in permanent damage to nerves,
tendons, muscles; loss of limbs
Skin grafting or amputation may be necessary
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
26
Extravasation (cont’d)


Prevention is essential
Continuous monitoring of the IV site is essential
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
27
Extravasation (cont’d)





If suspected, stop the infusion immediately and
contact the prescriber, but leave the intravenous
catheter in place
Aspirate any residual drug and/or blood from the
catheter
Consult guidelines or the pharmacist regarding
antidotes, application of hot or cold packs and/or
sterile occlusive dressings, and elevation and rest of
the affected limb
Thoroughly document the extravasation incident
Consult facility protocol and guidelines
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
28
Classroom Response Question
When handling and administering vesicant drugs the
nurse will:
A. double-flush the patient’s bodily secretions in the
commode.
B. use sterile towels to clean up after chemotherapy
spills.
C. mix chemotherapeutic drugs in the patient’s room.
D. teach the patient how to administer parenteral
chemotherapeutic drugs.
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
29
Nursing Implications


Assess baseline blood counts before
administering antineoplastic drugs
Follow specific administration guidelines for
each antineoplastic drug
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
30
Nursing Implications (cont’d)

Alkylating drugs

Monitor for expected effects of bone marrow
suppression
 Expect nausea, vomiting, diarrhea, stomatitis
 Hydration is important to prevent nephrotoxicity
 Report ringing/roaring in the ears—possible
ototoxicity
 Report tingling, numbness, or pain in extremities—
peripheral neuropathies may occur
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
31
Nursing Implications (cont’d)

Cytotoxic antibiotics





Expect bone marrow suppression, nausea, vomiting,
diarrhea, stomatitis
Monitor pulmonary status, since pulmonary fibrosis
may occur
Monitor for nephrotoxicity, liver toxicity
Monitor cardiovascular status
Daunorubicin may turn the urine a reddish color
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
32
Nursing Implications (cont’d)

In general:

Monitor closely for anaphylactic reactions
 Keep epinephrine, antihistamines, and
antiinflammatory drugs on hand
 Monitor closely for complications associated with
bone marrow suppression
• Anemia, thrombocytopenia, neutropenia
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
33
Nursing Implications (cont’d)

Cytoprotective drugs may be used to reduce
toxicities

IV amifostine to reduce renal toxicity associated with
cisplatin
 IV or PO allopurinol to reduce hyperuricemia
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
34
Nursing Implications (cont’d)

Monitor for oncologic emergencies

Infections
 Pulmonary toxicity
 Allergic reactions
 Stomatitis with severe ulcerations
 Bleeding
 Metabolic aberrations
 Bowel irritability with diarrhea
 Renal, liver, cardiac toxicity
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
35