Anticancer Drugs
Anticancer Drugs
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.
Management of cancer
There are three approaches for the
management of cancer:
1. Radiotherapy
2. Surgery
3. Chemotherapy
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
Classification of drugs
• Drugs acting directly on cells (cytotoxic
drugs):
1.Alkylating agents
• Mechlorethamine
• Cyclophosphamide
• Ifosfamide
• Chlorambucil
• Melphalan
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2. Antimetabolities
Methotrexate
6-mercaptopurine
6-thioguanine
Azathioprine
5-fluorouracil
Cytarabine
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3. Vinca alkaloids
Vincristine
Vinblastine
4. Taxanes
Paclitaxel
Docetaxel
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5. Antibiotics
Actinomycin D
Doxorubicin
Daunorubicin
Mitoxantrone
Bleomycins
Mitomycin C
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6. Miscellaneous
Hydroxyurea
Procarbazine
L-asparaginase
Cisplatin
Carboplatin
Imatinib
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• Drugs altering hormonal milieu
1.Glucocorticoids
• Prednisolone
2. Estrogens
• Fosfestrol
• Ethinylestradiol
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3. Selective estrogen receptor modulators
Tamoxifen
Toremifene
4. Aromatase inhibitors
Letrozole
Anastrozole
Exemestane
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5. Antiandrogen
Flutamide
Bicalutamide
6. 5 alpha reductase inhibitors
Finasteride
Dutasteride
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7. GnRH analogues
Nafarelin
Triptorelin
8. Progestins
Hydroxyprogestrone acetate
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
