world cancer report - iarc

MEDICINAL DRUGS
SUMMARY
> Certain drugs used to treat malignant
tumours, may rarely cause second
primary tumours.
> Drugs with hormonal activity or which
block hormonal effects may increase
risk of some hormonally-responsive cancers,
while reducing the risk of others.
> Drugs like diethylstilbestrol, which causes
vaginal cancer following transplacental
exposure, have been banned, while
use of others, like phenacetin (which
causes urothelial tumours), has been
restricted.
Modern medicine has at its disposal
hundreds of drugs, many of which are
essential for the effective treatment of
an enormous range of human diseases.
A small fraction of such drugs has been
found to have carcinogenicity to humans
as a side-effect. This is most likely for
some drugs that must be given at high
doses or for prolonged periods. Where
safer, non-carcinogenic alternatives
exist, such drugs have been withdrawn
from medical use. In certain cases, as in
the treatment of otherwise fatal diseases
such as disseminated cancer, the
risk of using drugs that present a carcinogenic
hazard is more than offset by
an immediate benefit to the patient.
Drugs that have been found to be carcinogenic
to humans include some antineoplastic
drugs and drug combinations
[1], certain hormones and hormone
antagonists [2,3], some immune suppressants
and a small number of miscellaneous
agents [1,4].
Anti-cancer drugs
Some antineoplastic agents and combined
drug therapies have caused secondary
cancers in patients (Table 2.13).
48 The causes of cancer
These agents have been evaluated by
the IARC Monographs on the Evaluation
of Carcinogenic Risks to Humans as carcinogenic
to humans (IARC Group 1).
Some of them are no longer used in
medicine because more effective and
less hazardous drugs have become
available. Other agents have properties
similar to the known carcinogens, and
are likely to be carcinogenic to humans
(IARC Group 2A) (Table 2.14). These
agents all have in common the ability
either to react chemically with DNA to
produce genetic damage at the cellular
level (e.g. procarbazine), or to interfere
with DNA replication in ways that can
produce genetic damage (e.g. etoposide)
(Medical oncology, p281). The
agents in Table 2.13 that have been
studied in animal experiments all cause
tumours. The potential of many effective
anti-tumour drugs to cause secondary
cancers in treated patients is well recognized.
Medical oncologists have
devoted much effort to optimizing the
doses of these drugs, in order to maximize
the anti-tumour effects while minimizing
risk of secondary cancers.
Hormones
Hormones are potent regulators of bodily
functions and hormonal imbalances
can cause increased risk of certain cancers
(Reproductive factors and hormones,
p76). This can occur when natural
or synthetic hormones are used for
Fig. 2.32 Histopathology of a clear cell carcinoma
of the vagina resulting from prenatal exposure to
diethylstilbestrol.
medical purposes, as in certain contraceptive
preparations and in postmenopausal
hormonal therapies.
Certain drugs have been developed that
counteract the effects of certain hormones
in specific tissues. Some of
these drugs have hormone-like effects
in other tissues, however, and can
increase risk of cancer at these sites.
Tamoxifen, for example, is an antiestrogen
that may be given to women with
estrogen receptor-positive breast
tumours to block estrogen from entering
the breast tissues. It is an effective
drug for prevention of contralateral
breast cancer in breast cancer patients,
but it also increases risk of cancer of
the endometrium [5]. Diethylstilbestrol
is a synthetic estrogen, originally prescribed
to prevent miscarriage, which
caused malformations of the reproductive
organs and is associated with
increased risk of vaginal adenocarcinoma
in daughters exposed to the drug in
utero (Fig. 2.32).
Other drugs and surgical implants
A small number of drugs that were used
in medicine for many years for a variety
of purposes other than antitumour, hormonal
or immunosuppressive therapies
have been found to present a risk of
cancer in humans when used in very
large quantities (e.g. phenacetin, contained
in analgesic mixtures, Fig. 2.33)
or for prolonged periods (e.g. Fowler's
Fig. 2.33 Histopathology of a transitional cell carcinoma
of the urinary tract caused by long-term
abuse of phenacetin-based analgesics.