Chemo

2. Introduction to chemotherapy
⚫Cancer is a disease characterised by disturbances in
cell survival, proliferation, and differentiation
(maturation of cells so they can carry out specified
functions). Cancer cells have a special ability to rapidly
proliferate (often leading to the production of a
tumour mass) and metastasise (or spread) to distan
TISSUE

3. ⚫Chemotherapy
It is defined as the use of cytotoxic (cell killing) drugs in the
treatment of cancer. Tumour cells are more sensitive than normal
cells to chemotherapeutic drugs because they are rapidly
dividing cells. Chemotherapy treatment disrupts the cell cycle in
an attempt to cause enough changes in the cellular makeup so
that the cell cannot divide, or damages the cellular makeup
enough to cause the cell to die. Some chemotherapeutic agents
are cell cycle specific (meaning they act on cells at a specific stage
of growth and division) while others can be given at any time in a
cells lifeand cause these terminal changes.

4. ⚫Chemotherapy drugs are sometimes given with the
intent to cure your disease. In other instances they
may be used aftersurgery toprevent recurrence or may
be used as a palliative measure tocontrol symptoms
and improve quality of life, rather than actually curing
disease (if this is not possible).

5. ⚫Chemotherapy often requires a combination of a number
of drugs in conjunction with other treatments such as
surgery and radiation therapy. Depending on the type of
drug used, it may be administered by mouth, intravenously
or directly into the affected organ. Chemotherapy regimens
vary greatly and may require several cycles of treatment
with drug‐free periods in between.

6. Chemotherapeutic classes
⚫Thereare fivechemotherapeuticclasses:
⚫Alkylating agents
⚫Anthracyclines
⚫Taxanes
⚫Vincaalkaloids
⚫Anti‐metabolites

7. ⚫Alkylating agents
⚫ Alkylating agents cause cell death by interacting with DNA
during cell synthesis. DNA is the component of cells
containing all the genetic information the cell needs to grow,
divide and function. The DNA is like the blue‐print of living
cells and has a special helical ladder structure. Alkylating
agents work by directly interacting with exposed DNA and
adding alkyl groups. The resulting permanent DNA damage
ultimately results in deathof thecells.
⚫ Cyclophosphamide (cycloblastin, endoxan) was the first
clinically effective cancer chemotherapy agent and is the most
commonly used alkylating agent. As well as its anti‐tumour
effects, it also has immunosuppressant activity as it also
disrupts the function of lymphocytes
⚫

8. ⚫Otheralkylating agents include chlorambucil (leukeran),
carmustine, lomustine and cisplatin.
Side effects of alkylating agents :
. nauseaand vomiting
.anaemia

9. ⚫Anthracyclines
⚫Anthracyclines are cytotoxic (cell killing) antibiotics
that are also non‐cell‐cycle specific chemotherapy
agents. They are probablyamoung the mostcommonly
used cytotoxic drugs. Many antracyclines also have
immunosuppressantactivity.
⚫Doxorubicin (adriamycin) is an example of an
anthracycline medication which is used in avarietyof
cancers including affecting
the breast, endometrium ovary, testicle, thyroid, stom
ach, bladder, liverand lung, soft tissues and several
childhood cancers. Epirubicin and mitozantrone are
otherexamples of anthracycline medications.

10. ⚫Side effects of anthracyclines
⚫Sideeffectsof anthracycline use include:
⚫Myelosuppression (bone marrow suppression) especiallyof
white blood cells, but also of red blood cells and platelets.
These side effects of chemotherapy can be minimised with
red blood cell and platelet transfusions. In addition if you
develop feverduring treatment
⚫Toxicity to the heart which may lead to arrhythmias.
Damage may become permanentafterapproximatelyone
month of treatment especially if you have been previously
exposed to these drugs. It is for this reason thatdoctors are
often reluctant to prescribeanthracyclines if you have been
treated with them in the past;

11. ⚫Severe local reactions, including tissue necrosis
(death) or extravasations (leakage of drug outside the
blood vessels);
⚫Secondary malignancies
⚫Radiation recall: The recurrence of skin damage from
previous radiotherapy
associated with
⚫Alopecia (hair loss): This may be
significanteffects on qualityof life;
⚫Nauseaand vomiting
⚫Oral ulceration

12. ⚫Taxanes
⚫Taxanes are cytotoxic agents that work on a protein called
tubulin found in the cytoplasm of cells. Tubulin is needed
for the production of microtubules which are essential in
cell division. Microtubules help separate chromosomes
(agents carrying our DNA) when cells divide. Taxanes are
generally used when other chemotherapy regimens have
failed. They tend to be effective against ovarian, breast and
lung cancers.
⚫Taxanes currently available in Australia include:
⚫Paclitaxel (Anzatax, Taxol);
⚫Nanoparticle albumin‐bound paclitaxel (Abraxane); and
⚫Docetaxal (Taxotere).
⚫Paclitaxel has been shown to have activity in a broad range
of solid tumours.

13. ⚫Sideeffectsof taxanes
Taxanes cause bone marrow suppression like manyother
chemotherapeutic agents. The most common effect is
neutropaenia, which increases thechance of infection.
Otherside effects include:
Nausea and vomiting: A variety of anti‐emetic (anti‐
nausea) agents are available for patients receiving
chemotherapy to help control and even eliminate
symptoms of nausea. Particularly useful agents are a class
of drugs called 5‐HT3 antagonists such as ondansetron
(Ondaz, Zofran) and granisetron combined with
dexamethasone (steroid). Otheranti‐emetics include
metoclopramide (Maxalon) and domperidone (Motilium);
⚫.

14. ⚫Diarrhoea
⚫Mouth sores;
⚫Jointand muscleaches;
⚫Alopecia (hair loss);
⚫Paraesthesia (abnormal sensation);
⚫Mild allergic reactions (flushing, shortness of
breath, urticaria (hives), rash);
⚫Anaphylactic reactions
⚫Injection site reactions

15. ⚫Vincaalkaloids
⚫Vinca alkaloids act on a specific phase of the cell cycle
called metaphase (M phase). They are another class of anti‐
tubulin agents (along with the taxanes) and work by
binding tubulin and inhibiting the production of
microtubules. This halts cell division and leads to cell
death. Vinca alkaloids are used to treat both
haematological (diseases of blood cells such as leukaemias)
and non‐haematological (solid organ) malignancies.
⚫There are four vinca alkaloids currently available namely
vinblastine, vincristine, vindesine and vinorelbine
(Navelbine).

16. ⚫Side effects of vinca alkaloids
⚫Vinca alkaloidscause a numberof thecommon side effects
seen with chemotherapy such as:
⚫Nauseaand vomiting
⚫Hair loss;
⚫Mouth sores;
⚫Headache;
⚫Constipation.

17. ⚫Anti‐metabolites
⚫Anti‐metabolites are molecules that have very similar
structures to true proteins within cells. They are therefore
taken up by cells which cannot distinguish the drug from
the real protein. Once inside the cell, anti‐metabolites
interact with DNA and RNA like the normal protein would
but due to slight variations in their properties prevent the
cell processes from continuing. Anti‐metabolites therefore
prevent normal proteins from binding in the cell and halt
normal function and division. In other words, they mimic
and interfere with the binding of real proteins. Once again
this leads to programmed cell death
Folateantagonists
⚫Methotrexate is the main folate antagonist. It may be used
in a variety of solid tumours and haematological
malignancies. In addition its immunosuppressant
properties may be utilised in the treatment of non‐
malignant conditions such as rheumatoid
arthritisand psoriasis.

18. ⚫Side effects of folate antagonists :
⚫Methotrexate is very toxic at high doses, particularly to
bone marrow and the digestive tract lining. Symptoms
of toxicity include:
⚫Bone marrow suppression, including bleeding,
anaemiaand increased risk of infection;
⚫Nausea;
⚫Anorexia;
⚫Diarrhoea raging from mild tosevere ulceration and
bleeding.
⚫Methotrexate is often administered with leucovorin,
which is an agentdesigned to reduce the anaemiaand
toxicity to normal cells that often accompanies
methotrexate therapy.

19. ⚫Purineantagonists
⚫Purine antagonists mimic the purines adenine and
guanine, two of the bases that make up DNA. By
mimicking these molecules, purine antagonists block
DNA synthesis and prevent cell division. Examples of
purine antagonists include 6‐mercaptopurine (Puri‐
Nethol), 6‐thioguanine, dacarbazine and fludurabine.
Purine antagonists are used for the treatment of
acute leukaemias.

20. Side effects of purine antagonists :
⚫The side effectsof 6‐mercaptopurine are listed below
which are similar to those seen with many other
chemotherapeuticagents. Theyare rare in children.
⚫Bone marrow suppression, resulting in increased bleeding
and infection risk;
⚫Mouth sores;
⚫Skin rash/acne;
⚫Mild nausea;
⚫Abnormal liver function;
⚫Hair loss.
⚫Anorexia, fever, fatigue/weaknessand facial flushing can
alsooccurwith other purin antagonists than 6‐
mercaptopurine.
⚫

21. ⚫Pyrimidineantagonists
⚫Pyrimidine antagonists mimic the pyrimidines cytosine
and thymine, the other two bases making up nucleotides
and DNA. By mimicking these molecules, pyrimidine
antagonists block DNA synthesis and prevent cell division
in a similar mechanism to purineantagonists.
⚫The pyrimidine antagonists include 5‐fluorouracil (Efudix),
cytarabine, capecitabine (Xeloda) and gemcitabine
(Gemzar). 5‐Flurouracil has a major role in the treatment
of gastrointestinal cancers. Capecitabine is an oral version
of 5‐fluorouracil and is used in the treatment of metastatic
colon cancer and metastatic or resistant breast cancer.
Cytarabine is used to treat leukaemias, and gemcitabine is
used in solid cancers such as ovarian or in combination
with cisplatin to treat non‐small cell lung cancer.
⚫

22. ⚫Side effects of pyrimidine antagonists :
⚫As 5‐fluorouracil is activeagainstdividing cells, italso
kills healthy cells, which contributes to the following
sideeffects:
⚫Nauseaand diarrhoea
⚫Bone marrow depression that may lead toanaemia
⚫Increased tendency to bruise
⚫Mouthsores
⚫Altered pigmentation of the skin