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P A R T 2
Chemotherapeutic agents
Therapeutic actions and indications
The mitotic inhibitors interfere with the ability of a
cell to divide; they block or alter DNA synthesis, thus
causing cell death. They work in the M phase of the cell
cycle. These drugs are used for the treatment of a variety
of tumours and leukaemias. See Table 14.4 for usual
indications for each of these agents.
Pharmacokinetics
Generally, these drugs are given intravenously because
they are not well absorbed from the GI tract. They are
metabolised in the liver and excreted primarily in the
faeces, making them safer for use in people with renal
impairment than the antineoplastics that are cleared
through the kidney.
Contraindications and cautions
These drugs should not be used during pregnancy or
breastfeeding
because of the potential risk to the fetus or
neonate
. Use caution when giving these drugs to anyone
with a known allergy to the drug or related drugs. Care
is necessary for individuals with the following condi
tions: bone marrow suppression,
which is often the
index for redosing and dosing levels
; renal or hepatic
dysfunction,
which could interfere with the metabolism
or excretion of these drugs and often indicates a need
to change the dose
; and known GI ulcerations or ulcer
ative diseases,
which may be exacerbated by the effects
of these drugs.
Adverse effects
Adverse effects frequently encountered with the use of
mitotic inhibitors include bone marrow suppression,
with leucopenia, thrombocytopenia, anaemia and pan
cytopenia, secondary to the effects of the drugs on the
rapidly multiplying cells of the bone marrow. GI effects
include nausea, vomiting, anorexia, diarrhoea and
mucous membrane deterioration. As with the other
antineoplastic agents, effects of the mitotic inhibitors
may include possible hepatic or renal toxicity, depend
ing on the exact mechanism of action. Alopecia may
also occur. These drugs also cause necrosis and celluli
tis if extravasation occurs, so it is necessary to regularly
monitor injection sites and take appropriate action as
needed.
Clinically important drug–drug interactions
Mitotic inhibitors that are known to be toxic to the liver
or the CNS should be used with care with any other
TABLE 14.4
DRUGS IN FOCUS Mitotic inhibitors (continued)
Drug name
Dosage/route
Usual indications
vincristine (generic)
Adult: 1.4 mg/m
2
IV at weekly intervals
Treatment of acute leukaemia, various
lymphomas and sarcomas
Special considerations:
extensive CNS
effects are common; GI toxicity, local
irritation at injection IV site and hair
loss commonly occur; syndrome of
inappropriate secretion of antidiuretic
hormone (SIADH) has been reported—
monitor urine output and arrange for fluid
restriction and diuretics as needed
vinorelbine (Navelbine)
30 mg/m
2
IV once weekly, based on
granulocyte count or 60–80 mg/m
2
PO
once weekly
First-line treatment of unresectable
advanced non–small cell lung cancer;
stage IV non–small-cell once weekly lung
cancer and stage III non–small cell lung
cancer with cisplatin
Special considerations:
GI and CNS
toxicity are common; total loss of hair,
local reaction at injection site and bone
marrow depression also occur; prepare a
calendar with return dates for the series of
injections; avoid extravasation but arrange
for hyaluronidase infusion if it occurs;
antiemetics may be helpful if reaction is
severe
Safe medication administration
Special care needs to be taken when administering these
drugs. The care provider should avoid any skin, eye or
mucous membrane contact with the drug. This type of
contact can cause serious reactions and toxicity.
