198
P A R T 2
Chemotherapeutic agents
GI effects include nausea, vomiting, anorexia, diarrhoea
and mucous membrane deterioration, all of which are
related to the drugs’ effects on the rapidly multiplying
cells of the GI tract. Hepatic toxicity and renal toxicity
may occur, depending on the exact mechanism of
action.
Alopecia
, or hair loss, related to effects on the
hair follicles, may also occur. All drugs that cause cell
death can cause a potentially toxic increase in uric acid
levels. In 2006, a new drug,
rasburicase
, was introduced
to manage uric acid levels in children (see Box 14.4).
Clinically important drug–drug interactions
Alkylating agents that are known to cause hepatic or
renal toxicity should be used cautiously with any other
drugs that have similar effects. In addition, drugs that
are toxic to the liver may adversely affect drugs that are
metabolised in the liver or that act in the liver (e.g. oral
anticoagulants). Always check for specific drug–drug
interactions for each agent in a drug guide.
Amifostine (
Ethyol
) is a cytoprotective (cell-protecting)
drug that preserves healthy cells from the toxic effects
of cisplatin. It is thought to react to the specific acidity
and vascularity of non-tumour cells to protect them, and
it may also act as a scavenger of free radicals released
by cells that have been exposed to cisplatin. Amifostine
is given at a dose of 910 mg/m
2
four times a day as a
15-minute IV infusion starting within 30 minutes after
starting cisplatin therapy; timing is very important to its
effectiveness. Now approved for use to prevent the renal
toxicity associated with the use of cisplatin in individuals
with advanced ovarian cancer, amifostine is under
investigation as an agent for protecting lung fibroblasts
from the effects of paclitaxel. Because amifostine is
associated with severe nausea and vomiting, concurrent
administration of an antiemetic is recommended. It
also can cause hypotension and individuals should be
monitored closely for this condition.
Mesna (
Uromitexan
) is a cytoprotective agent that
is used to reduce the incidence of haemorrhagic cystitis
caused by ifosfamide or cyclophosphamide. Mesna,
which is known to react chemically with urotoxic
metabolites of ifosfamide, is given intravenously at the
time of the ifosfamide injection at a dose that is 20%
of the ifosfamide dose and is repeated 4 and 8 hours
afterwards. Because mesna has been associated with
nausea and vomiting, an antiemetic may be useful.
■■
BOX 14.3
Drugs that protect cells from alkylating
agents
Rasburicase (
Fasturtec
) was approved in 2006 for the
management of plasma uric acid levels in children with
leukaemia, lymphoma and solid tumour malignancies
who are receiving antineoplastic therapy associated with
tumour lysis and subsequent elevated serum uric acid
levels. It is administered as a single daily IV infusion
of 0.15 to 0.2 mg/kg over 30 minutes for 5 days.
Chemotherapy should be started 4 to 24 hours after
the first dose of rasburicase. Uric acid levels should be
monitored frequently, using prechilled, heparinised vials
that are kept in an ice-water bath. This analysis should
be done within 4 hours of each rasburicase dose.
■■
BOX 14.4
Drug to manage rising uric acid levels
associated with tumour lysis
Prototype summary: Chlorambucil
Indications:
Palliative treatment of chronic
lymphocytic leukaemia, malignant lymphomas
and Hodgkin’s disease.
Actions:
Alkylates cellular DNA, interfering with the
replication of susceptible cells.
Pharmacokinetics:
Route Onset
Peak
Duration
Oral
Varies
1 hour
15–20 hours
T
1/2
:
60 to 90 minutes, metabolised in the liver and
excreted in the urine.
Adverse effects:
Tremors, muscle twitching,
confusion, nausea, hepatotoxicity, bone marrow
suppression, sterility, cancer.
Care considerations for
people receiving alkylating agents
Assessment: History and examination
■
■
Assess for contraindications or cautions: history
of allergy to any of the alkylating agents
to
avoid hypersensitivity reactions
; bone marrow
suppression
to prevent further suppression
; renal
or hepatic dysfunction
that might interfere with
drug metabolism and excretion
; and current status
related to pregnancy or breastfeeding
to prevent
potentially serious adverse effects on the fetus or
breastfeeding baby
.
■
■
Perform a physical assessment
to establish baseline
data for determining the effectiveness of the
drug and the occurrence of any adverse effects
associated with drug therapy
.
■
■
Assess orientation and reflexes
to evaluate any
central nervous system (CNS) effects
; respiratory
rate and adventitious sounds
to monitor the disease
and to evaluate for respiratory or hypersensitivity
effects
; pulse, rhythm and auscultation to monitor
for systemic or cardiovascular effects; and bowel
sounds and mucous membrane status
to monitor
for GI effects
.
