previous adverse effects to the cytotoxic drug. Doses may
also differ depending on whether a drug is used alone or in
combination.
Because of the complexity of dosage regimens in the
treatment of malignant disease, dose statements have been
omitted from many of the drug entries in this chapter.Cytotoxic drugs: effect on pregnancy and
reproductive function
Most cytotoxic drugs are teratogenic and should not be
administered during pregnancy, especially during thefirst
trimester. Exclude pregnancy before treatment with
cytotoxic drugs. Considerable caution is necessary if a
pregnant woman presents with cancer requiring
chemotherapy, and specialist advice should always be
sought.
Contraceptive advice should be given to men and women
before cytotoxic therapy begins (and should cover the
duration of contraception required after therapy has ended).
Alkylating drugs can have an adverse effect on
gametogenesis, which may be reversible particularly in
females. Regimens that do not contain an alkylating drug or
procarbazine may have less effect on fertility, but those with
an alkylating drug or procarbazine carry the risk of causing
permanent male sterility (there is no effect on potency).
Pretreatment counselling and consideration of sperm
storage may be appropriate. Women are less severely
affected, though the span of reproductive life may be
shortened by the onset of a premature menopause. No
increase in fetal abnormalities or abortion rate has been
recorded in patients who remain fertile after cytotoxic
chemotherapy. Amenorrhoea may occur, which also may be
reversible.Management of cytotoxic drug side-effects
Gastro-intestinal effects
Management of gastrointestinal effects of cytotoxic drugs
includes the use of antacids, H 2 -receptor antagonists, and
proton pump inhibitors to protect the gastric mucosa,
laxatives to treat constipation, and enteral and parenteral
nutritional support.Oral mucositis
Good oral hygiene keeps the mouth clean and moist and
helps to prevent mucositis; prevention is more effective than
treatment of the complication. Good oral hygiene measures
for children over 6 months include brushing teeth with a soft
small brush withfluoride toothpaste 2 – 3 times daily, and
rinsing the mouth frequently. Dailyfluoride supplements
can be used on the advice of the child’s dental team. For
children under 6 months or when it is not possible to brush
teeth, carers should be instructed how to clean the mouth
using an oral sponge moistened with water or with an
antimicrobial solution such as diluted chlorhexidine.
Mucositis related to chemotherapy can be extremely painful
and may, in some circumstances, require opioid analgesia.
Secondary infection with candida is frequent; treatment with
a systemically absorbed antifungal, such asfluconazole
p. 374 , is effective.Nausea and vomiting
Nausea and vomiting cause considerable distress to many
children who receive chemotherapy, and to a lesser extent
abdominal radiotherapy, and may lead to refusal of further
treatment; prophylaxis of nausea and vomiting is therefore
extremely important. Symptoms may be acute (occurring
within 24 hours of treatment), delayed (first occurring more
than 24 hours after treatment), or anticipatory (occurring
prior to subsequent doses). Delayed and anticipatory
symptoms are more difficult to control than acute symptoms
and require different management.
Susceptibility to nausea and vomiting may increase with
repeated exposure to the cytotoxic drug.Drugs may be divided according to their emetogenic
potential and some examples are given below, but the
symptoms vary according to the dose, to other drugs
administered, and to the individual’s susceptibility to
emetogenic stimuli.
Mildly emetogenic treatment—fluorouracil, etoposide
p. 549 , low doses of methotrexate p. 543 , the vinca alkaloids,
and abdominal radiotherapy.
Moderately emetogenic treatment—carboplatin p. 548 ,
doxorubicin hydrochloride p. 539 , intermediate and low
doses of cyclophosphamide p. 535 , mitoxantrone p. 540 ,and
high doses of methotrexate.
Highly emetogenic treatment—cisplatin p. 548 , dacarbazine
p. 536 , and high doses of alkylating drugs.
Anti-emetic drugs, when given regularly, help prevent or
ameliorate emesis associated with chemotherapy in children.
Prevention of acute symptoms: For patients at low risk
of emesis, pretreatment with a 5 HT 3 -receptor antagonist
may be of benefit.
For patients at high risk ofemesisor when other treatment
is inadequate, a 5 HT 3 -receptor antagonist is often highly
effective. The addition of dexamethasone p. 439 and other
anti-emetics may also be required.
Prevention of delayed symptoms: dexamethasone, given
by mouth, is the drug of choice for preventing delayed
symptoms; it is used alone or with metoclopramide
hydrochloride p. 262. Due to the risks of neurological side-
effects, metoclopramide hydrochloride should only be used
in children as a second-line option. The 5 HT 3 -receptor
antagonists may have a role in preventing uncontrolled
symptoms. Aprepitant p. 263 given in combination with a
5 HT 3 -receptor antagonist (with or without dexamethasone)
is licensed for prevention of nausea and vomiting associated
with highly and moderately emetogenic cancer
chemotherapy.
Prevention of anticipatory symptoms: Good symptom
control is the best way to prevent anticipatory symptoms.
Lorazepam p. 222 can be helpful for its amnesiac, sedative,
and anxiolytic effects.
Bone-marrow suppression
All cytotoxic drugs except vincristine sulfate p. 550 and
bleomycin p. 547 cause bone-marrow suppression. This
commonly occurs 7 to 10 days after administration, but is
delayed for certain drugs, such as melphalan p. 537.
Peripheral blood counts must be checked before each
treatment. The duration and severity of neutropenia can be
reduced by the use of granulocyte-colony stimulating
factors; their use should be reserved for children who have
previously experienced severe neutropenia.
Cytotoxic drugs may be contra-indicated in children with
acute infection; any infection should be treated before, or
when starting, cytotoxic drugs.
Infection in a child with neutropenia requires immediate
broad-spectrum antibacterial treatment that covers all likely
pathogens. Appropriate bacteriological investigations
should be conducted as soon as possible. Children taking
cytotoxic drugs who have signs or symptoms of infection (or
their carers) should be advised to seek prompt medical
attention. All children should be investigated and treated
under the supervision of an appropriate oncology or
haematology specialist. Antifungal treatment may be
required in a child with prolonged neutropenia or fever
lasting longer than 4 – 5 days. Chickenpox and measles can be
particularly hazardous in immunocompromised children.
Varicella-zoster immunoglobulin p. 775 is indicated if the
child does not have immunity against varicella and has had
close contact with infectious chickenpox or herpes zoster.
Antiviral prophylaxis can be considered in addition to
varicella-zoster immunoglobulin or as an alternative if
varicella–zoster immunoglobulin is inappropriate. If an
immunocompromised child has come into close contact with532 Cytotoxic responsive malignancy BNFC 2018 – 2019
Immune system and malignant disease8