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Back to Oncology Procedures
Chemotherapy
Chemotherapy (pronounced keem-o-therapy) is the use of certain drugs
to treat disease, as distinct from other forms of treatment, such as
surgery. Chemotherapy dates at least as far back as the use, by the
Indians of Peru, of cinchona bark in the treatment of fevers, such as
malaria. The first modern chemotheraputic agent was Paul Ehrlich's
arsphenamine, an arsenic compound discovered in 1909 and used to treat
syphilis. This was later followed by sulfonamides discovered by Domagk
and penicillin G discovered by Alexander Fleming.
Please note that today, the term chemotherapy is mostly used for the
drug treatment of cancer, and the rest of this article discusses that
topic. Antibiotics are referred to as antibacterial chemotherapy, but
in medical practice this word is only used in the context of the
treatment of tuberculosis.
Other uses of chemotherapy agents (including the ones mentioned below)
are the treatment of autoimmune disease (DMARDs).
Chemotherapy for cancer
Cancer is the uncontrolled growth of cells due to damage to DNA
(mutations) and, occasionally, due to an inherited propensity to
develop certain tumors.
Broadly, chemotheraputic drugs work by selectively targeting
fast-dividing cells. As these drugs cause damage to cells they are
termed cytotoxic. Some drugs cause cells to commit apoptosis
(effectively cell suicide), but generally chemotheraputic drugs block
some essential feature of the cell division process which makes cells
unable to divide.
Unfortunately, scientists have yet to be able to locate specific
features of cancerous cells that would make them uniquely targetable.
This means that other fast dividing cells such those responsible for
hair growth and replacement of epithelium in the intestine are also
affected. However, some drugs have a better side-effect profile than
others, enabling doctors to adjust treatment regimens to the advantage
of patients in certain situations.
As chemotherapy affects cell division, tumors with a high growth
fractions (such as acute myelogenous leukemia and the
lymphomas,
including Hodgkin's disease) are more sensitive to chemotherapy, as a
larger proportion of the tumor cells are undergoing cell division at
any time.
Chemotherapeutic drugs affect "younger" tumors (i.e. less
differentiated) more effectively, because at a higher grade of
differentiation, the propensity to growth decreases. In 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 brachytherapy and, of course,
surgery.
Types of drugs
The majority of chemotherapeutic drugs can be divided in to: alkylating
agents, anti-metabolites, plant alkaloids, and antitumor agents. As
all of the drugs affects DNA synthesis or function in some way, they
are categorized by their effect on the cell cycle.
Some newer agents cannot be classified. This include the new tyrosine kinase inhibitor imatinib mesylate (Gleevec? or Glivec?), which
directly targets a molecular abnormality in certain types of
cancer
(Chronic myelogenous leukemia,
Gastrointestinal stromal cell
tumors).
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Plant alkaloids
These alkaloids are derived from plants and block cell division by
preventing microtubules being synthesized. These are vital for cell
division and without them it can not occur. The main examples are
vinca alkaloids such as vincristine.
Hormonal therapy
A number of malignancies responds to hormonal therapy.
- Steroids (often dexamethasone) can inhibit tumor growth or the
associated edema (brain tumors.
- Prostate cancer is often sensitive to finasteride, an agent that
blocks the peripheral conversion of testosterone to
5-hydroxy-testosterone.
- Breast cancer is often positive to the estrogen and/or progesterone
receptor. Inhibiting the production (aromatase inhibitors)or action (tamoxifen)
of these hormones can often be used as an adjunct to therapy.
- Some other tumors are also hormone dependent, although the specific
mechanism is still unclear.
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Treatment schemes
There are a number of strategies in the administration of
chemotherapeutic drugs used today. Combined modality chemotherapy is
the use of drugs with other cancer treatments, such as radiation
therapy or surgery. 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
minimizing the chances of resistance developing to any one agent.
Adjuvant Chemotherapy 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 tumor 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
tumors are fast-dividing, and therefore very susceptible.
Delivery
Most chemotherapy is delivered intravenously. Depending on the
patient, the cancer type, the
stage of cancer, the
type of chemotherapy,
and the dosage, IV chemotherapy may be given on either an inpatient or
outpatient basis. A few agents are given orally, such as prednisone
and melphalan. Chemotherapy may be delivered through a central line,
giving more reliable access to the circulatory system while preventing
phlebitis in peripheral veins.
Side-effects
The treatment can be physically exhausting for the patient. Current
chemotherapeutic techniques have a range of
side effects mainly
affecting the fast-dividing cells of the body. Important common
side-effects include (dependent on the agent):
- hair loss
- nausea and vomiting
- diarrhea or constipation
- anemia
- depression of the immune system hence (potentially lethal) infections
and sepsis
- hemorrhage
- secondary neoplasms
- cardiotoxicity
- hepatotoxicity
- nephrotoxicity
Virtually all chemotherapeutic regimens can cause depression of the
immune system, often by paralysing the bone marrow and leading to a
decrease of white blood cells, red blood cells and platelets. The
latter two, when they occur, are improved with blood transfusion.
Neutropenia (a decrease of the neutrophil granulocyte count below 0.5
x 109/litre) can be improved with synthetic G-CSF (granulocyte-colony
stimulating factor, filgrastim, Neupogen?, Neulasta?) or GM-CSF.
In very severe myelosupression, which occurs in some regimens, almost
all the bone marrow stem cells (cells which produce white and red
blood cells) are destroyed, meaning allogenic or autogenic bone marrow
cell transplants are necessary. (In autogenic BMTs, cells are removed
from the patient before the treatment, multiplied and then re-injected
afterwards; in allogenic BMTs the source is a donor.) However, some
patients still develop diseases because of this interference with bone
marrow.
Nausea and vomiting induced by chemotherapy can be alleviated with
antiemetics. Usually metoclopramide or 5 hydroxytryptamine 3 (5-HT3)
receptor antagonists (dolasetron, granisetron, ondansetron) are used.
Some studies and patient groups claim that the use of cannabinoids
derived from marijuana during chemotherapy greatly reduces the
associated nausea and vomiting, and enables the patient to eat.
Chemotherapy may increase the risk of
cardio-vascular disease and
occasionally leads to secondary cancer.
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