C h a p t e r 7
Neoplasia
151
used. Drugs used in combinations are individually
effective against the tumor and synergistic with each
other. The maximum possible drug doses usually are
used to ensure the maximum cell kill within the range
of toxicity tolerated by the host for each drug. Routes
of administration and dosage schedules are carefully
designed to ensure optimal delivery of the active forms
of the drugs to the tumor during the sensitive phase of
the cell cycle.
Chemotherapy Side Effects.
Unfortunately, chemo-
therapeutic drugs affect both cancer cells and the rapidly
proliferating cells of normal tissue, producing undesir-
able side effects. Some side effects appear immediately
or after a few days (acute), some within a few weeks
(intermediate), and others months to years after chemo-
therapy administration (long term).
Most chemotherapeutic drugs suppress bone marrow
function and formation of blood cells, leading to anemia,
neutropenia, and thrombocytopenia. With neutropenia,
there is risk for developing serious infections, whereas
thrombocytopenia increases the risk for bleeding. The
availability of hematopoietic growth factors (e.g., gran-
ulocyte colony-stimulating factor [G-CSF]); erythropoi-
etin, which stimulates red blood production; and IL-11,
which stimulates platelet production) has shortened the
period of myelosuppression, thereby reducing the need
for hospitalizations due to infection and decreasing the
need for blood products.
Anorexia, nausea, and vomiting are common prob-
lems associated with cancer chemotherapy.
58
The severity
of the vomiting is related to the emetic potential of the
particular drug. These symptoms can occur within min-
utes or hours of drug administration and are thought to
be due to stimulation of the chemoreceptor trigger zone
in the medulla that stimulates vomiting (see Chapter 28).
The chemoreceptor trigger zone responds to the level
of chemicals circulating in the blood. The acute symp-
toms usually subside within 24 to 48 hours and often
can be relieved by antiemetic drugs. The pharmacologic
approaches to prevent chemotherapy-induced nausea and
vomiting have greatly improved over several decades. The
development of serotonin (5-HT
3
) receptor antagonists
has facilitated the use of highly emetic chemotherapy
drugs by more effectively reducing the nausea and vomit-
ing induced by these drugs.
Alopecia or hair loss results from impaired prolifera-
tion of the hair follicles and is a side effect of a number
of cancer drugs; it usually is temporary, and the hair
tends to regrow when treatment is stopped. The rap-
idly proliferating structures of the reproductive system
are particularly sensitive to the action of cancer drugs.
Women may experience changes in menstrual flow or
have amenorrhea. Men may have a decreased sperm
count (i.e., oligospermia) or absence of sperm (i.e., azo-
ospermia). Many chemotherapeutic agents also may
have teratogenic or mutagenic effects leading to fetal
abnormalities.
58
Chemotherapy drugs are toxic to all cells. Because they
are potentially mutagenic, carcinogenic, and teratogenic,
special care is required when handling or administering
the drugs. Drugs, drug containers, and administration
equipment require special disposal as hazardous waste.
60
Hormone and AntihormoneTherapy
Hormonal therapy consists of administration of drugs
designed to deprive the cancer cells of the hormonal sig-
nals that otherwise would stimulate them to divide. It is
used for cancers that are responsive to or dependent on
hormones for growth and have specific hormone recep-
tors.
61
Among the tumors that are known to be respon-
sive to hormonal manipulation are those of the breast,
prostate, and endometrium. Other cancers, such as
Kaposi sarcoma and renal, liver, ovarian, and pancreatic
cancer, are also responsive to hormonal manipulation,
but to a lesser degree.
The therapeutic options for altering the hormonal
environment in the woman with breast cancer or the
man with prostate cancer include surgical and phar-
macologic measures. Surgery involves the removal
of the organ responsible for the hormone produc-
tion that is stimulating the target tissue (e.g., ovaries
in women or testes in men). Pharmacologic methods
focus largely on reducing circulating hormone levels
or changing the hormone receptors so that they no
longer respond to the hormone. Pharmacologic sup-
pression of circulating hormone levels can be effected
through pituitary desensitization, as with the admin-
istration of androgens, or through the administration
of
gonadotropin-releasing hormone
(GnRH) analogs
that act at the level of the hypothalamus to inhibit
gonadotropin production and release. Another class of
drugs, the
aromatase inhibitors
, is used to treat breast
cancer; these drugs act by interrupting the biochemi-
cal processes that convert the adrenal androgen andro-
stenedione to estrone.
62
Hormone receptor function can be altered by the
administration of pharmacologic doses of exogenous
hormones that act by producing a decrease in hormone
receptors or by antihormone drugs (antiestrogens and
antiandrogens) that bind to hormone receptors, mak-
ing them inaccessible to hormone stimulation. Initially,
patients often respond favorably to hormonal treat-
ments, but eventually the cancer becomes resistant to
hormonal manipulation, and other approaches must be
sought to control the disease.
Biotherapy
Biotherapy involves the use of immunotherapy and
biologic response modifiers as a means of changing a
person’s immune response and modifying tumor cell
biology. It involves the use of monoclonal antibodies,
cytokines, and adjuvants.
63
Monoclonal Antibodies.
Recent advances in the ability
to manipulate the genes of immunoglobulins have resulted
in the development of a wide array of monoclonal antibod-
ies directed against tumor-specific antigens as well as sig-
naling molecules.
64
These include
chimeric
human-murine
(mouse) antibodies with human constant region and
murine-variable regions (see Chapter 15, Figure 15-10),
