Anticancer
Chemotherapy, in its most general sense, refers to
treatment of disease by chemicals that kill cells, specifically
those of micro-organisms or
ancer.
In popular usage, it usually refers to
antineoplastic drugs used to treat
ancer
or the combination of these drugs into a
standardized treatment regimen.
In its non-ncological
use, the term may also refer to
antibiotics (antibacterial chemotherapy). In that sense, the
first modern chemotherapeutic agent was
Paul Ehrlich's
arsphenamine, an arsenic compound discovered in 1909 and used to treat
yphilis.
This was later followed by
sulfonamides discovered by
Domagk and
penicillin discovered by
Alexander Fleming.
Other uses of cytostatic chemotherapy agents (including the ones
mentioned below) are the treatment of
autoimmune diseases such as
multiple sclerosis and
rheumatoid arthritis and the suppression of
transplant rejections (see
immunosuppression and
DMARDs).
History
The use of
chemical substances and drugs as
edication
dates back to the ancient
ndian system
of medicine called
yurveda
which uses many metals besides herbs for treatment of a large number of
ailments. More recently,
Persian physician,
Muhammad ibn Zakarīya Rāzi (Rhazes), in the 10th century, introduced the use
of chemicals such as
vitriol, opper,
mercuric and
arsenic alts,
al
ammoniac, old
coria,
halk,
lay,
oral,
earl,
ar,
itumen and
lcohol for
medical purposes.
The first drug used for cancer chemotherapy, however, dates back to the early
20th century, though it was not originally intended for that purpose.
Mustard gas was used as a
chemical warfare agent during
orld War
I and was studied further during
orld
War II. During a military operation in World War II, a group of people were
accidentally exposed to mustard gas and were later found to have very low white
blood cell counts.
It was reasoned that an agent that damaged the rapidly growing white blood cells
might have a similar effect on cancer. Therefore, in the 1940s, several patients
with advanced lymphomas (cancers of certain white blood cells) were given the
drug by vein, rather than by breathing the irritating gas. Their improvement,
although temporary, was remarkable.
That experience led researchers to look for other substances that might have
similar effects against cancer. As a result, many other drugs have been
developed to treat cancer, and drug development since then has exploded into a
multi-billion dollar industry. The targeted-therapy revolution has arrived, but
the principles and limitations of chemotherapy discovered by the early
researchers still apply.
Principles
ancer is
the uncontrolled growth of
cells coupled with
alignant
behavior: invasion and
etastasis.
Cancer is thought to be caused by the interaction between
enetic
susceptibility and environmental toxins.
Broadly, most chemotherapeutic drugs work by impairing
itosis (ell
division), effectively targeting
fast-dividing cells. As these drugs cause damage to cells they are termed
cytotoxic. Some drugs cause cells to undergo
poptosis
(so-called "programmed cell death").
Unfortunately, scientists have yet to identify specific features of malignant
and immune cells that would make them uniquely targetable (barring some recent
examples, such as the
Philadelphia chromosome as targeted by
matinib).
This means that other fast dividing cells such as those responsible for
air growth and for
replacement of the
ntestinal
pithelium
(lining) are also often affected. However, some drugs have a better
side-effect profile than others, enabling
octors
to adjust treatment regimens to the advantage of patients in certain situations.
As chemotherapy affects cell division, tumors with high growth fractions
(such as
acute myelogenous leukemia and the aggressive
ymphomas,
including
Hodgkin's disease) are more sensitive to chemotherapy, as a larger
proportion of the targeted cells are undergoing
ell
division at any time. Malignancies with slower growth rates, such as
indolent lymphomas, tend to respond to chemotherapy much more modestly.
Drugs affect "younger" tumors (i.e. more differentiated) more effectively,
because mechanisms regulating cell growth are usually still preserved. With
succeeding generations of tumor cells, differentiation is typically lost, growth
becomes less regulated, and tumors become less responsive to most
chemotherapeutic agents. Near the center of some solid tumors, cell division has
effectively ceased, making them insensitive to chemotherapy. Another problem
with solid tumors is the fact that the chemotherapeutic agent often does not
reach the core of the tumor. Solutions to this problem include
radiation therapy (both
brachytherapy and
teletherapy) and
urgery.
Over time, cancer cells become more resistant to chemotherapy treatments.
Recently, scientists have identified small pumps on the surface of cancer cells
that actively move chemotherapy from inside the cell to the outside. Research on
p-glycoprotein and other such chemotherapy efflux pumps, is currently
ongoing. Medications to inhibit the function of
p-glycoprotein are undergoing testing as of June, 2007 to enhance the
efficacy of chemotherapy.
Treatment schemes
There are a number of strategies in the administration of chemotherapeutic
drugs used today. Chemotherapy may be given with a curative intent or it may aim
to prolong life or to palliate symptoms.
Combined modality chemotherapy is the use of drugs with other
ancer
treatments, such as
radiation therapy or
urgery. Most
cancers are now treated in this way. Combination chemotherapy is a
similar practice which involves treating a patient with a number of different
drugs simultaneously. The drugs differ in their mechanism and side effects. The
biggest advantage is minimising the chances of resistance developing to any one
agent.
In
neoadjuvant chemotherapy (preoperative treatment) initial
chemotherapy is aimed for shrinking the primary tumour, thereby rendering local
therapy (surgery or radiotherapy) less destructive or more effective.
Adjuvant chemotherapy (postoperative treatment) can be used when
there is little evidence of cancer present, but there is risk of recurrence.
This can help reduce chances of resistance developing if the tumour does
develop. It is also useful in killing any cancerous cells which have spread to
other parts of the body. This is often effective as the newly growing tumours
are fast-dividing, and therefore very susceptible.
Palliative chemotherapy is given without curative intent, but simply
to decrease tumor load and increase life expectancy. For these regimens, a
better toxicity profile is generally expected.
All chemotherapy regimens require that the patient be capable of undergoing
the treatment.
Performance status is often used as a measure to determine whether a patient
can receive chemotherapy, or whether dose reduction is required.
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