2. Introduction
Cancer refers to a malignant neoplasm or new
growth. Cancer cells manifest uncontrolled
proliferation, loss of function due to loss of
capacity to differentiate, invasiveness, and the
ability to metastasize.
Cancer arises as a result of genetic changes in
the cell, the main genetic changes being,
inactivation of tumor suppressor genes and
activation of oncogenes.
3. Management of cancer
There are three approaches for the management
of cancer:
1. Radiotherapy
2. Surgery
3. Chemotherapy
4. Anticancer drugs
• The anticancer drugs either kill cancer cells or
modify their growth. However selectivity of
majority of drugs is limited and they are one of
the most toxic drugs used in therapy.
• In malignant diseases, drugs are used with the
aim of:
1. Cure or prolonged remission
2. Palliation
3. Adjuvant chemotherapy
14. General toxicity of cytotoxic
drugs
Bone marrow depression
Lymphoreticular tissue: lymphocytopenia and
inhibition of lymphocyte function.
Oral cavity: the oral mucosa is particularly
susceptible to cytotoxic drugs because of high
epithelial cell turnover.
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GIT: Diarrhea, shedding of mucosa, hemorrhages
occur due to decrease in the rate of renewal of
the mucous lining. Drugs that frequently cause
mucositis are Bleomycins, Actinomycin, and
Methotrexate.
Nausea and vomiting are prominent with many
cytotoxic drugs, this is due to direct stimulation of
CTZ.
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Gonads: Inhibition of gonadal cells causes
oligozoospermia and impotence in males;
inhibition of ovulation and amenorrhea are
common in females.
Fetus: practically all cytotoxic drugs given to
pregnant women profoundly damage the
developing of the fetus.
Hyperuricaemia: this is a secondary to a massive
cell destruction (uric acid is a product of purine
metabolism). Gout and urate stones in the urinary
tract may develop. Allopurinol is protective by
decreasing uric acid synthesis.
17. Mechanism of actions
Alkylating agents and related compounds (e.g.
cyclophosphamide, lomustine, thiotepa, cisplatin):
These groups of drugs act by forming covalent
bonds with DNA and thus impending DNA
replication.
Antimetabolites (e.g. methotrexate, fluorouracil,
mercaptopurine): These drugs blocks or
destabilize pathways in DNA synthesis.
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Cytotoxic antibiotics (e.g. Doxorubucin,
bleomycin, dactinomycin): These drugs inhibit
DNA or RNA synthesis or cause fragmentation to
DNA chains or interfere with RNA polymerase and
thus inhibit transcription.
Plant derivatives (e.g. vincristine): Inhibits mitosis
19. Mechlorethamine
It is the first nitrogen mustard, highly reactive and
local vesicant, can only be given i.v route.
It produces many acute effects like nausea,
vomiting, and haemodynamic changes.
Dose is 0.1mg/kg i.v daily times 4 days, doses
may be repeated at suitable intervals.
It is available 1omg dry powder in vial.
20. Cyclophosphamide
It is inactive, produces few acute effects and is
not locally damaging. Transformation into active
metabolities occurs in the liver and a wide range
of antitumour actions is excerted.
It has prominent immunosuppressant property.
Thus it is one of the most popular anticancer
drugs.
It is less damaging to platelets, but alopecia and
cystitis are prominent.
Dose is 2-3mg/kg/day, 10-15mg/kg i.v, every 7-
10days, i.m use is also possible.
21. Ifosfamide
Ifosfamide has a longer and dose dependent
halflife.
It has found utility in bronchogenic, breast,
testicular, bladder, headache, neck and some
other carcinoma.
Ifosfamide causes less alopecia, and is less
emetogenic than cyclophosphamide.
Dose is available 1g vial, 200mg inj.
22. Chlorambucil
It is very slow acting Alkylating agent specially
active on lymphoid tissue.
It is the drug of choice for long term maintenance
therapy for chronic lymphatic leukemia and some
solid tumors also resolve.
It has some immunosuppressant property.
Dose is 4-10mg daily for 3-6 weeks.
23. Melphalan
It is very effective in multiple myeloma and has
been used in advanced ovarian cancer.
Bone marrow depression is the most important
toxicity.
Infections, diarrhea, and pancreatitis are the
complications.
Dose is 10mg daily for 7 days or 6mg per day for
2-3 weeks.
It is available 2, 5, 50mg for i.v injection.
24. Busulfan
It is highly specific for myeloid elements,
granulocyte precursors being the most sensitive,
followed by those platelets and RBC. It produces
little effect on lymphoid tissue and G.I.T.
Hyperuricaemia is common and pulmonary
fibrosis is a speacific adverse effect. Sterility also
occurs. It is the drug of choice for chronic myeloid
leukemia.
The dose is 2-6mg/day orally.
25. Dacarbazine
It is different from other Alkylating agents in
having primary inhibitory action on RNA and
protein synthesis (others mainly effect DNA).
It is activated in the liver. The most important
indication is malignant melanoma, also used
Hodgkin's disease.
Nausea and vomiting are the prominent side
effects.
The dose is 3.5mg/kg per day i.v for 10 days.
Available 100, 200, 500mg injection.
26. Methotrexate
It is one of the oldest and highly efficacious
antineoplastic drugs, inhibits dihydrofolate
reductase- blocking the conversion of DHF to
THF which is an essential co-enzyme required for
one carbon transfer reactions in purine synthesis.
Methotrexate is absorbed orally. Little is
metabolized and largely excreted in the urine.
Methotrexate is apparently curative in
choriocarcinoma, 15-30mg/day for 5 days orally
or 20-40mg i.m or i.v.
