200
P A R T 2
Chemotherapeutic agents
ANTIMETABOLITES
Antimetabolites (see Table 14.2) are drugs that have
chemical structures similar to those of various natural
metabolites that are necessary for the growth and
division of rapidly growing neoplastic cells and normal
cells. Antimetabolites include azacitidine (
Vidaza
),
capecitabine (
Xeloda
), cladribine (
Leustatin, Litak,
Movectro
), clofarabine (
Evoltra
), colaspase (
Leunase
),
cytarabine (generic), fludarabine (
Farine, Fludara
),
fluorouracil (
Efudix
), gemcitabine (
Gemcite, Gemzar
),
mercaptopurine (
Puri-Nethol
), methotrexate (
Metho-
blastin
), pemetrexed (
Alimta
), raltitrexed (
Tomudex
)
and thioguanine (
Lanvis
).
Therapeutic actions and indications
Antimetabolites inhibit DNA production in cells that
depend on certain natural metabolites to produce
their DNA. They replace these needed metabolites and
thereby prevent normal cellular function. Many of these
agents inhibit thymidylate synthetase, DNA polymerase
or folic acid reductase, all of which are needed for DNA
synthesis. They are considered to be S phase specific in
the cell cycle. They are most effective in rapidly dividing
cells, preventing cell replication and leading to cell death
(see Figure 14.5). The antimetabolites are indicated for
the treatment of various leukaemias and some GI and
basal cell cancers (see Table 14.2 for usual indications
for each agent). Use of these drugs has been somewhat
limited because neoplastic cells rapidly develop resist
ance to these agents. For this reason, these drugs are
usually administered as part of a combination therapy.
one and 8 mg dexamethasone PO on days two to four,
and 32 mg ondansetron IV on day one only.
• Two benzodiazepines—alprazolam (
Xanax
), 0.5 mg
PO four times a day, and lorazepam (
Ativan
), 2 to
6 mg/day PO—seem to be effective in directly
blocking the CTZ to relieve nausea and vomiting
caused by cancer chemotherapy; they are especially
effective when combined with a corticosteroid.
• Haloperidol (
Haldol
), 0.5 to 2.0 mg PO four times
a day, or 2 to 25 mg intramuscularly (IM) or IV, is
a dopaminergic blocker that also is believed to have
direct CTZ effects.
• Metoclopramide (
Maxolon
), 2 mg/kg IV over at least
30 minutes, calms the activity of the GI tract; it is
especially effective if combined with a corticosteroid,
an antihistamine, and a centrally acting blocker such
as haloperidol or lorazepam.
• Prochlorperazine (
Stemetil
), 5 to 10 mg PO three to
four times a day, or 5 to 10 mg IM, is a phenothiazine
that has been found to have strong antiemetic action
in the CNS; it can be given by a variety of routes.
Nausea and vomiting are unavoidable aspects of
many chemotherapeutic regimens. However, treating the
person as the chemotherapy begins, using combination
regimens, and providing plenty of supportive and
comforting care can help to alleviate some of the distress
associated with these adverse effects.
■■
BOX 14.5
Antiemetics and cancer chemotherapy
(continued)
TABLE 14.2
DRUGS IN FOCUS Antimetabolites
Drug name
Dosage/route
Usual indications
azacitidine (Vidaza)
Dosage: 75 mg/m
2
per day SC for 7 days q
4 weeks
Treatment of myelodysplastic syndrome
Special considerations:
premedicate
for nausea; monitor for bone marrow
suppression; avoid pregnancy or fathering
children while on drug
capecitabine (Xeloda)
2,500 mg/m
2
per day PO in two divided doses
for 2 weeks, then 1 week of rest, for three
cycles
Dukes C colon cancer: 1250 mg/m
2
PO b.d.
for 2 weeks, then 1 week of rest for a total of
eight 3-week cycles
Treatment of metastatic breast cancer with
resistance to paclitaxel or anthracyclines;
treatment of metastatic colorectal cancer
as first-line therapy treatment of breast
cancer with docetaxel in people with
metastatic disease; postsurgery Dukes C
colon cancer
Special considerations:
severe diarrhoea
can occur—monitor hydration and
nutrition; monitor for bone marrow
suppression
cladribine (Leustatin, Litak,
Movectro)
0.09 mg/kg per day IV for 7 consecutive days
Treatment of active hairy cell leukaemia
Special considerations:
severe bone
marrow depression can occur—monitor
person closely and reduce dose as
needed; fever is common, especially
early in treatment
