Transcript Chapter 21 outline

Chapter 21:
Antineoplastic Drugs
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Chapter 21 Outline

Antineoplastic Drugs

Use of antineoplastic agents
 Mechanisms of action
 Classification
 Adverse drug effects
 Combinations
 Dental implications
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2
Antineoplastic Drugs


Designed to treat malignancies


Haveles (p. 269)
May also be used for the treatment of diseases
with an inflammatory component
The dental health care worker should be
aware of the timing of treatments and the
effect on bone marrow

Side effects include oral manifestations
cont’d…
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3
Antineoplastic Drugs

Mechanisms involved in the etiology of
cancer include genetics, viruses, deleted or
damaged tumor suppressor genes, specific
oncogenes, and changes in both ribonucleic
acid (RNA) and deoxyribonucleic acid (DNA)
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4
Use of Antineoplastic Agents


Haveles (pp. 269-270) (Box 21-1)
Antineoplastic agents are used clinically to
interfere with neoplastic cells



Suppress growth and attempt to destroy and
prevent the spread of malignant cells
May be used alone or in combination or with
radiation or surgery
Current philosophy involves treating the initial
stages of the disease very aggressively
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5
Mechanisms of Action



Haveles (pp. 270-271) (Fig. 21-1)
Efficacy is based primarily on their ability to
interfere with the metabolism or the
reproductive cycle of tumor cells
Four stages in the cycle

G1: the postmitotic or pre-DNA synthesis phase
 S: period of DNA synthesis
 G2: premitotic or post-DNA synthesis phase
 M: period of mitosis
cont’d…
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6
Mechanisms of Action

Most antineoplastic agents are labeled as

Cell-cycle specific: effective only at certain phases
of cell growth
 Cell-cycle nonspecific: effective at all stages of the
cycle

Resistance is either

De novo: the neoplasm was always resistant
 Acquired resistance: resistance through natural
selection of mutations
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Classification


Haveles (pp. 271-272) (Fig. 21-2; Box 21-2)
Antineoplastic agents are divided into groups,
depending on their mechanism and site of action


Alkylating agents contain alkyl radicals that react with
DNA in all cycles of the cell to prevent reproduction
Antimetabolites attack cells in the S period of
reproduction by interfering with purine or pyrimidine
synthesis
• They are more effective on rapidly proliferating neoplasms
cont’d…
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Classification

Miscellaneous antineoplastics

Plant alkaloids: mitotic inhibitors and arrest cells in
metaphase
 Antibiotics: cell-cycle nonspecific and are effective for
solid tumors
 Hormones: interrupt the cell cycle at the G stage
 Steroids: used to suppress lymphocytes in leukemias
and lymphomas and in combination therapies
 Estrogens: used palliatively in operative breast cancer
 Tamoxifen: used to manage breast cancer
 Cisplatin: cell-cycle nonspecific
 Hydroxyurea: inhibits ribonucleotide reductase, which
interferes with RNA synthesis
 Procarbazine: produces chromosomal breakage
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Adverse Drug Effects











Haveles (pp. 272-274)
Bone marrow suppression
Osteonecrosis
Gastrointestinal (GI) effects
Dermatologic effects
Hepatotoxicity
Neurologic effects
Nephrotoxicity
Immunosuppression
Germ cells
Oral effects
cont’d…
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10
Adverse Drug Effects


Haveles (pp. 272-273) (Table 21-2)
Rapidly growing cells are more susceptible to
inhibition or destruction by antineoplastic
agents

Some normal cells have a faster reproductive
cycle than slowly growing tumor cells
 Because cells of the GI tract, bone marrow, and
hair follicles are among the faster growing normal
cells, early side effects are associated with these
tissues
cont’d…
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Adverse Drug Effects


Bone marrow suppression: inhibition results in
leukopenia or agranulocytosis,
thrombocytopenia, and anemia


Haveles (p. 273)
Symptoms may include susceptibility to infection,
bleeding, and fatigue
Osteonecrosis: a recently recognized adverse
effect of bisphosphonates

94% of all cases of osteonecrosis have been reported
in cancer patients receiving intravenous
bisphosphonates for multiple myeloma or metastatic
carcinoma
cont’d…
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Adverse Drug Effects


GI effects: sloughing of GI mucosa can produce
many symptoms


Haveles (p. 273)
May be expressed as nausea, stomatitis, oral
ulcerations, vomiting, and hemorrhagic diarrhea
Dermatologic effects: cutaneous reactions vary
from mild erythema and maculopapular
eruptions to exfoliative dermatitis and StevensJohnson syndrome

Alopecia is frequent
cont’d…
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Adverse Drug Effects


Hepatotoxicity: liver problems occur primarily
with antimetabolites
Neurologic effects: peripheral neuropathy,
ileus, inappropriate antidiuretic hormone
secretion, and convulsions have been
associated primarily with vincristine or
vinblastine
cont’d…
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Adverse Drug Effects



Nephrotoxicity: renal tubular impairment occurring
secondary to hyperuricemia is caused by rapid cell
destruction and release of nucleotides
Immunosuppression: enhanced susceptibility to
infection or a second malignancy may occur after
treatment
Germ cells: inhibition is frequent, at least
temporarily

Mutations within germ cells may occur
cont’d…
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15
Adverse Drug Effects


Haveles (p. 274) (Box 21-3)
Oral effects: primarily discomfort, sensitivity of
the teeth and gums, mucosal pain and
ulceration, gingival hemorrhage, dryness, and
impaired taste sensation


Infection of oral mucosa from leukopenia and
bleeding from thrombocytopenia can occur
Patients may experience inflammation of the
mouth, xerostomia, or glossitis
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16
Combinations


Haveles (p. 274)
Agents with different mechanisms of action
are often used together to inhibit the
reproduction of neoplastic cells in all phases

Mixtures may act synergistically, leading to
enhanced cytotoxicity with fewer side effects
cont’d…
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Combinations


Haveles (p. 274)
Used in lower doses to treat diseases
associated with inflammation or autoimmune
conditions and transplants


Diseases include rheumatoid arthritis, systemic
lupus erythematosus, pemphigus vulgaris, and
psoriasis
Doses of these agents used to treat diseases with
an autoimmune component are often lower than
the doses used to treat cancer
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Dental Implications


Haveles (p. 274) (Boxes 21-3, 21-4)
The best times for oral hygiene procedures
are when they would coincide with the
presence of the highest level of formed blood
elements

This time frame would be either just before
treatment or on the first few days of treatment
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19
Antineoplastic Agents by Group


Haveles (p. 272) (Box 21-2)
Alkylating agents


Nitrogen mustard
• mechlorethamine (Mustargen)
• cyclophosphamide, chlorambucil (Leukeran)
• melphalan (Alkeran)
• uracil mustard
• ifosfamide (Ifex)
Nitrosoureas
• carmustine (BCNU) (BiCNU)
• lomustine (CCNU) (CeeNU)
• semustine (Methyl-CeeNU)
• streptozocin (Zanosar)
• estramustine (Emcyt)
cont’d…
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20
Antineoplastic Agents by Group


Haveles (p. 272) (Box 21-2)
Alkylating Agents

Miscellaneous
• busulfan (Myleran)
• pipobroman (Vercyte)
• thiotepa
• cisplatin (Platinol)
• carboplatin (Paraplatin)
cont’d…
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21
Antineoplastic Agents by Group


Haveles (p. 272) (Box 21-2)
Antimetabolites



Folic acid analog
• methotrexate (Amethopterin)
Pyrimidine analog
• fluorouracil (5-FU)
• floxuridine (FUDR)
• cytosine arabinoside (ARA-C) (Cytosar-U)
• azacitidine
Purine analog
• mercaptopurine (6-MP) (Purinethol)
• thioguanine (6-TG)
• cladribine (Leustatin)
• fludarabine (Fludara)
• pentostatin (Nipent)
cont’d…
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22
Antineoplastic Agents by Group


Haveles (p. 272) (Box 21-2)
Miscellaneous antineoplastics


Plant alkaloids
• vinblastine (Velban)
• vincristine (Oncovin)
Antibiotics
• dactinomycin (Actinomycin-D, Cosmegen)
• doxorubicin (Adriamycin)
• bleomycin (Blenoxane)
• mitomycin-C (Mutamycin)
• plicamycin (Mithramycin, Mithracin)
• daunorubicin (Cerubidine)
cont’d…
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23
Antineoplastic Agents by Group


Haveles (p. 272) (Box 21-2)
Miscellaneous antineoplastics

Hormones
• Adrenocorticosteroids (prednisone)
• Androgen


testolactone (Teslac)
fluoxymesterone (Halotestin)
• Antiandrogen



flutamide (Eulexin)
nilutamide (Nilandron)
bicalutamide (Casodex)
• Estrogen


diethylstilbestrol
ethinyl estradiol (Estinyl)
cont’d…
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24
Antineoplastic Agents by Group


Haveles (p. 272) (Box 21-2)
Miscellaneous antineoplastics

Hormones
• Antiestrogen




tamoxifen (Nolvadex)
raloxifene (Evista)
fulvestrant (Faslodex)
toremifene (Fareston)
• Aromatase inhibitors



anastrozole (Arimidex)
exemestane (Aromasin)
letrozole (Femara)
cont’d…
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25
Antineoplastic Agents by Group


Haveles (p. 272) (Box 21-2)
Miscellaneous antineoplastics

Hormones
• Progestin


medroxyprogesterone
megestrol (Megace)
• goserelin (Zoladex)
• leuprolide (Lupron)
cont’d…
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26
Antineoplastic Agents by Group


Immune modulators





Haveles (p. 272) (Box 21-2)
levamisole (Ergamisol)
interferon α-n3 (Alferon N)
interferon α-2b (Intron A)
interferon α-2a (Roferon-A)
Podophyllotoxin derivatives


etoposide (VePesid)
teniposide (Vumon)
cont’d…
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27
Antineoplastic Agents by Group


Haveles (p. 272) (Box 21-2)
Aminobisphosphonates

alendronate (Fosamax)
 ibandronate (Boniva)
 pamidronate (Aredia)
 risedronate (Actonel)
 zoledronic acid (Zometa)
cont’d
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28
Antineoplastic Agents by Group


Haveles (p. 272) (Box 21-2)
Other

L-asparaginase (Elspar)
 hydroxyurea (Hydrea)
 procarbazine (Matulane)
 paclitaxel (Taxol)
 altretamine (Hexalen)
 trastuzumab (Herceptin)
 imatinib mesylate (Gleevec)
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29