A Textbook of Clinical Pharmacology and Therapeutics

DRUGSUSED INCANCERCHEMOTHERAPY 371

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 gas-
tro-intestinal tract flora. Effective isolation is achieved in pur-
pose-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,
netilmicinoramikacin) plus a broad-spectrum ureidopeni-
cillin (e.g. piperacillin) may be used. Alternatively, monother-
apy with a third- or fourth-generation cephalosporin active
againstβ-lactamase-producing organisms (e.g. ceftazidime,
cefotaximeorcefipime) can provide suitable empiric cover-
age. 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

Doxorubicin,ifosfamide, parenteral etoposide, camptothe-
cins, anti-metabolites, vinca alkaloids and taxanes all com-
monly cause alopecia. This may be ameliorated in the case of
doxorubicinby cooling the scalp with, for example, ice-cooled
water caps. Some hair loss occurs with many cytotoxic agents.

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 menstru-

ation when treatment is stopped and pregnancy is then pos-

sible, 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 malforma-

tions 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 (particu-

larly those who received both chemotherapy and radiation

therapy) develop a second malignancy, usually acute non-

lymphocytic leukaemia. This malignancy is also approxi-

mately 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.

10 000

5000

500

1000

(^100) 03 9 1521 03 915 21 27 33 39 45 51 57
(a) (b)
Partial recovery
Secondary fall
Polymorph count/mm
3
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).
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;