Kee: Pharmacology, 8th Edition

Chapter 37: Anticancer Drugs

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Cancer is a group of diseases in which abnormal cells grow out of control and may spread
to other areas of the body. Although some cancers are inherited, most develop when
genes in a normal cell become damaged or lost (mutation). More than one mutation is
required before a malignancy can develop. Therefore the development of cancer is a
multistep process that may take years to complete.
Pharmaceuticals are often used to destroy cancer cells and are called by different names,
including anticancer drugs, cancer chemotherapeutic agents, antineoplastic drugs, or
cytotoxic therapy. Chemotherapy may be used as the sole treatment of cancer or in
conjunction with other modalities (e.g., radiation, surgery, biologic response modifiers).
Combination chemotherapy has proved to be effective in curing some cancers.
If cancer can no longer be controlled, chemotherapy may be used to relieve diseaserelated symptoms or improve quality of life. This is called palliative treatment.
Cancer is a genetic disease. Genetic defects may occur in a variety of ways, including
deletion, translocation, duplication, inversion, or insertion of genetic material. When
these defects cannot be effectively repaired, cells exhibit abnormal characteristics and
unregulated growth.
Proto-oncogenes are normal genes that are involved in the controlled growth, division,
and apoptosis of cells.
An oncogene is a mutation in a proto-oncogene. An abnormal oncogene can affect
cellular growth-control proteins and trigger unregulated cell division.
Tumor-suppressor (TS) genes signal a cell to cease multiplying and act to stop the action
of oncogenes. If TS genes become lost or dysfunctional, cells could reproduce
uncontrollably.
A number of viruses are associated with the development of cancer.
Bacteria can play a role in the development of cancer.
Environmental factors associated with the development of cancer include tobacco use,
diet, infectious agents, chemicals, excessive sun exposure, and radiation.
Anticancer drugs cause cell death by interfering with cell replication and are classified
according to their action on the cell. Cell cyclenonspecific (CCNS) drugs act during any
phase of the cell cycle, including the G0 phase. Cell cyclespecific (CCS) drugs exert
their influence during a specific phase or phases of the cell cycle.
Growth fraction and doubling time are two factors that play a major role in the response
of cancer cells to anticancer drugs. Anticancer drugs are more effective against neoplastic
cells that have a high growth fraction.
Anticancer drugs are not selective, so both cancer cells and normal cells are affected. The
side effects of chemotherapy are largely related to the toxic effects on normal cells.
Chemotherapy administration is guided by specific protocols that were developed based
on the results of controlled research studies. Chemotherapy is usually given in cycles to
improve the likelihood that cancer cells will be destroyed and that normal cells can
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recover.
Chemotherapy is most effective when it is able to kill cells in all phases of the cell cycle.
Anticancer drugs exert adverse effects on rapidly growing normal cells (e.g., skin, hair).
These drugs can also affect cells in the gastrointestinal (GI) tract, mucous membranes,
bone marrow, and the reproductive system.
Patients receiving highly potent drugs at home may need to be closely monitored for
severe adverse reactions or to assure adequate hydration.
One of the largest groups of anticancer drugs is the alkylating compounds. Alkylating
agents cause cross-linking of DNA strands, abnormal base pairing, or DNA strand breaks,
thus preventing the cell from dividing. Drugs in this group belong to the CCNS category
and kill cells in various and multiple phases of the cell cycle. However, they are most
effective against cells in the G0 phase.
The side effects for alkylating drugs include nausea, vomiting, hemorrhagic cystitis,
alopecia, anemia, leukopenia, thrombocytopenia, bone marrow suppression, secondary
malignancies, and sterility.
Antimetabolites resemble natural metabolites that synthesize, recycle, and break down
organic compounds for use by the body. However, antimetabolites disrupt metabolic
processes and can inhibit enzyme synthesis. They are classified as CCS and exert their
effects in the S phase (DNA synthesis and metabolism) of the cell cycle.
The general side effects of antimetabolite drugs include bone marrow suppression,
stomatitis, nausea, vomiting, alopecia, and hepatic and renal dysfunction.
Antitumor antibiotics inhibit protein and RNA synthesis and bind DNA, causing
fragmentation.
Adverse reactions to the antitumor antibiotics are similar to other antineoplastics and
include alopecia, nausea, vomiting, stomatitis, and myelosuppression. Antitumor
antibiotics are capable of causing vesication.
Plant alkaloids are derived from natural products that are CCS and block cell division at
the M phase of the cell cycle.
Adverse reactions to plant alkaloids include leukopenia, hypersensitivity reactions,
partial-to-complete alopecia, constipation, nausea, vomiting, diarrhea, and phlebitis. The
plant alkaloids damage peripheral nerve fibers and may cause reversible or irreversible
neurotoxicity.
A more recent change in the delivery of chemotherapy involves the use of anticancer
drugs that have been packaged inside synthetic fat globules called liposomes. The fatty
coating helps the chemotherapy drug remain in the system longer, decreases side effects,
and increases the duration of therapeutic effects.
Although hormones are not considered true chemotherapeutic agents, several classes of
hormonal agents are used in the treatment of cancer. These include corticosteroids, sex
hormones, antiestrogens, aromatase inhibitors, gonadotropin-releasing hormone
analogues, and antiandrogens.
Corticosteroids are anti-inflammatory agents that suppress the inflammatory process that
is associated with tumor growth.
Cortisone derivatives taken internally produce many adverse side effects, including fluid
retention, potassium loss, increased risk of infection, increase in blood sugar, increased

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fat distribution, muscle weakness, increased bleeding tendency, and euphoria.

The sex hormones or hormone-like agents are used to slow the growth of hormonedependent tumors.
Adverse reactions to progestins include fluid retention and thrombotic disorders. If
androgen therapy is used over a long period of time, masculine secondary sexual
characteristics, such as body hair growth, lowering of the voice, and muscle growth, will
occur. Side effects associated with antiestrogens include hot flashes, irregular menses,
fatigue, headaches, nausea, and vomiting. Men who take antiestrogens may experience
headaches, impotence, and a decreased interest in sexual activity.
Luteinizing hormone-releasing hormone (LH-RH) agonists suppress the secretion of
follicle-stimulating hormone and luteinizing hormone from the pituitary gland.
Antiandrogens work by binding to androgen receptors and blocking the effects of
dihydrotestosterone on the prostate cancer cells.
The aromatase inhibitors block the peripheral conversion of androgens to estrogens, thus
suppressing the postmenopausal synthesis of estrogen and slowing tumor growth.
Vaccines used to prevent cancer include the hepatitis B vaccine, given to prevent
infection with the hepatitis B virus, which can cause liver cancer. Two recombinant
vaccines, Gardasil and Cervarix, are given to girls and young women to prevent human
papillomavirus (HPV) infections that can cause cervical cancer. Cervarix is used for boys
and young men to prevent HPV types 6 and 11, which can cause genital warts.

Copyright 2015, 2012, 2009, 2006, 2003, 2000, 1997, 1993 by Saunders, an imprint of Elsevier Inc.