A Textbook of Clinical Pharmacology and Therapeutics

Polymorph count/mm 3
(a) (b)
10 000
5000
1000
500
targeted (e.g. sunitinib, trastuzumab) therapies seldom cause
myelosuppression.
INFECTION
Infection is a common and life-threatening complication of
chemotherapy. It is often acquired from the patient’s own gastro-intestinal
tract flora. Effective isolation is achieved in purpose-built
laminar-airflow units, but this does not solve the
problem of the patient’s own bacterial flora. Classical signs of
infection – other than pyrexia – are often absent in neutropenic
patients, and constant vigilance is required to detect and treat
septicaemia early. Broad-spectrum antibiotic treatment must
be started empirically in febrile neutropenic patients before the
results of blood and other cultures are available. Combination
therapy with an aminoglycoside active against Pseudomonas
and other Gram-negative organisms (e.g. tobramycin,
netilmicin or amikacin) plus a broad-spectrum ureidopenicillin
(e.g. piperacillin) may be used. Alternatively, monotherapy
with a third- or fourth-generation cephalosporin active
against β-lactamase-producing organisms (e.g. ceftazidime,
cefotaxime or cefipime) can provide suitable empiric coverage.
Therapeutic decisions need to be guided by knowledge of
local organisms, the patient’s previous antimicrobial therapy
and culture results (see Chapter 43). Opportunistic infections
with fungi or protozoa (e.g. Pneumocystis carinii) can occur;
details of the treatment for such infections are to be found in
Chapters 43, 45 and 46.
ALOPECIA
Partial recovery
Secondary fall
100
03 9 15 21 03 9 15 21 27 33 39 45 51 57
Therapy Therapy
Figure 48.3: Patterns of bone marrow recovery following
cytotoxic therapy: (a) rapid (17–21 days) and (b) delayed (initial
fall 8–10 days, secondary nadir at 27–32 days, recovery 42–50
days) (after DE Bergasagel).
Doxorubicin, ifosfamide, parenteral etoposide, camptothecins,
anti-metabolites, vinca alkaloids and taxanes all commonly
cause alopecia. This may be ameliorated in the case of
doxorubicin by cooling the scalp with, for example, ice-cooled
water caps. Some hair loss occurs with many cytotoxic agents.
DRUGS USED IN CANCER CHEMOTHERAPY 371
INFERTILITY AND TERATOGENESIS
Cytotoxic drugs predictably impair fertility and cause fetal
abnormalities. Most women develop amenorrhoea if treated
with cytotoxic drugs. However, many resume normal menstruation
when treatment is stopped and pregnancy is then possible,
especially in younger women who are treated with lower
total doses of cytotoxic drugs. In men, a full course of cytotoxic
drugs usually produces azoospermia. Alkylating agents are
particularly harmful. Recovery can occur after several years.
Sperm storage before chemotherapy can be considered for
males who wish to have children in the future. Reproductively
active men and women must be advised to use appropriate
contraceptive measures during chemotherapy, as a reduction in
fertility with these drugs is not universal and fetal malformations
could ensue. It is best to avoid conception for at least six
months after completion of cytotoxic chemotherapy.
SECOND MALIGNANCY
Up to 3–10% of patients treated for Hodgkin’s disease (particularly
those who received both chemotherapy and radiation
therapy) develop a second malignancy, usually acute nonlymphocytic
leukaemia. This malignancy is also approximately
20 times more likely to develop in patients with
ovarian carcinoma treated with alkylating agents with or
without radiotherapy. This delayed treatment complication is
likely to increase in prevalence as the number of patients who
survive after successful cancer chemotherapy increases.
Key points
Adverse effects of cytotoxic chemotherapy
• Immediate effects:
– nausea and vomiting (e.g. cisplatin,
cyclophosphamide);
– drug extravasation (e.g. vinca alkaloids,
anthracyclines, e.g. doxorubicin).
• Delayed effects:
– bone marrow suppression – all drugs;
– infection;
– alopecia;
– drug-specific organ toxicities (e.g. skin and
pulmonary – bleomycin; cardiotoxicity – doxorubicin);
– psychiatric-cognitive morbidity;
– teratogenesis.
• Late effects:
– gonadal failure/dysfunction;
– leukaemogenesis/myelodysplasia;
– development of secondary cancer.
DRUGS USED IN CANCER CHEMOTHERAPY
These include the following:
1. alkylating agents;
2. antimetabolites;