The document provides information on antineoplastic agents (anticancer drugs). It defines cancer and describes the two types of tumors - malignant and benign. It then discusses the stages of the cell cycle and characteristics of cancer cells. The document covers various classes of antineoplastic agents including alkylating agents, platinum complexes, antimetabolites, microtubule damaging agents, antibiotics, and topoisomerase inhibitors. It provides details on specific drugs like cyclophosphamide, cisplatin, methotrexate, and actinomycin D.

1. ANTINEOPLASTIC AGENTS
As per syllabus prescribed by PCI for D. pharmacy second year.
-Ambareen Fatima Ahmed
Lecturer,
School of Pharmaceutical Science,
Integral University, Lucknow.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

2. • Cancer is defined by American cancer society as, ‘A group of diseases
characterized by uncontrolled growth and the spread of abnormal cells that left
untreated may lead to death.’
• Neoplasia, a term related to this definition is, ‘The uncontrolled growth of new
tissue, the product of which is known as a tumor or neoplasm.’
• Neoplasms are new and diseased form of tissue growth.
• Tumors are of two types, malignant and benign.
1) Malignant tumor has the capability of invading surrounding tissues and
moving to distant locations in the body (Through blood vessels and lymphatic
system).
This process of moving to different parts of the body is known as metastasis.
2) Benign tumors does not invade (enter) nearby tissues or spread to other parts
of the body

3. STAGES OF CELL CYCLE
In eukaryotic cells, the stages of the cell cycle are divided into two
major phases: Interphase and the Mitotic (M) phase.
Interphase is divided into three phases, G1, S, and G2 phase.
During interphase, the cell grows and makes a copy of its DNA.
G1 phase: also called the first gap phase, the cell grows
physically larger, copies organelles, and makes the molecular
building blocks.
S phase. In S phase, the cell synthesizes a complete copy of the
DNA in its nucleus.
G2 phase: Also called the second gap phase, the cell grows
more, makes proteins and organelles, and begins to reorganize its
contents in preparation for mitosis. G2 phase ends when mitosis
begins.
During the mitotic phase, the cell separates its DNA into two sets
and divides its cytoplasm, forming two new cells.
The prefix inter- means between. Thus, interphase takes place
between one mitotic phase and the next.

4. •Two characteristics of cell proliferation are;
1) DNA synthesis and mitosis to produce new cells.
2) Cell differentiation which produce specialized cells.
•These processes are controlled by growth factors
and growth inhibitors.
•Cancer cells show four distinguishing properties
from the normal cells. These are,
i ) Uncontrolled proliferation
ii) De-differentiation and loss of function.
iii) Invasiveness
iv) Metastasis

5. ➢A normal cell turns into a cancer cell because of one or more mutations into its DNA.
➢These mutations can be inherited or acquired through exposure to viruses and carcinogens.
CHEMICALS, VIRUSES,
IRRADIATION, Etc.
ACQUIRED
MUTATIONS
INHERITED
MUTATIONS
ALTERED GENE EXPRESSION
UNCONTROLLED CELL PROLIFERATION,
DE- DIFFERENTIATION.
DECREASED APOPTOSIS
DEVELOPMENT OF PRIMARY TUMOR
INVASION TO NEARBY TISSUE BY
TUMOR CELLS
METASTASIS
DEVELOPMENT OF
SECONDARY TUMOR
Cancer is a genetic disease—that is,
it is caused by changes in genes that
control the way cells function,
especially how they grow and divide.
Genetic changes that cause cancer
can be inherited from parents.
They can also arise during a person’s
lifetime as a result of errors that
occur as cells divide or because of
damage to DNA caused by certain
environmental exposures.
Cancer-causing environmental
exposures include substances, such
as the chemicals in tobacco smoke,
and radiation, such as ultraviolet rays
from the sun. Image source: cancer.gov

6. TREATMENT
• Treatment of cancer generally involves surgical removal followed by radiation and
chemotherapy.
• Chemotherapy refers to drugs that are used to kill cells, which includes both
antibiotics and agents used in the treatment of cancer.
• Drugs used for the treatment of cancer are referred to as anticancer agents or
antineoplastic agents.
• Anticancer drugs either kill cancer cells or modify their growth. But, selectivity of
majority of drugs is limited. Thus, they are one of the most toxic drugs used in
therapy.

7. Cytotoxic drugs
I) Alkylating agents
a) Nitrogen mustards
e.g. Cyclophosphamide, Chlorambucil
b) Ethylene imines
e.g. Thiotepa
c) Alkyl sulfonate
e.g. Busulfan
d) Nitrosoureas
e.g. Carmustine, Lomustine
II) Platinum complex
e.g. Cisplatin, Carboplatin
III) Antimetabolites
a) Folate antagonist
e.g. Methotrexate
b) Purine antagonist
e.g. 6- mercaptopurine
6- thioguanine
Azathioprine
c) Pyrimidine antagonist
e.g. 5- fluorouracil
IV) Microtubule damaging agents
e.g. Vincristine, Vinblastine, Paclitaxel
V) Antibiotics
e.g. Actinomycin D (Dactinomycin)
Daunorubicin, Mitomycin C.
VI) Topoisomerase-1 Inhibitors
e.g. Topotecan
VII) Topoisomerase-2 Inhibitors
e.g. Etoposide
CLASSIFICATION OF ANTINEOPLASTICS

8. Alkylating agents:
MOA: Act by alkylation of DNA, RNA and proteins.
Mostly act by alkylation of DNA. After alkylation, the alkylated site gets cleaved
(breaks) resulting in formation of single strands of nuclear DNA.
1) Cyclophosphamide
Physical properties
1) White crystalline powder 2) Odourless 3) Slight bitter taste
4) Soluble in water 5) Aqueous solutions have acidic pH.
Stability: Unstable at room temperature. Hydrolysis occurs above 30⸰C. Darkens on
exposure to light.
Storage: Stored in well closed, light resistant containers at temperature below 30⸰C.
Use: Treatment of variety of cancers. (Tumors) such as, carcinoma of breast, lungs
and ovary. And in lymphoma, leukaemia and myeloma.
Brand: 1) Endoxan 50 mg tablet
2) Cycloxan 200, 500, 1000 mg injection

9. 2) Chlorambucil
Physical properties
1) White to pale beige crystalline or granular
powder
2) Slight odour.
3) Insoluble in water. The sodium salt is soluble
in water.
Stability: Sensitive to light and heat.
Storage: Stored in well closed, light resistant
containers.
Use: Hodgkin’s lymphoma, and chronic
lymphocytic leukaemia in combination with
prednisone and as a single agent.
Brand: 1) Leukeran 2, 5 mg tab
3) Busulfan
Physical properties:
1) White crystals or powder
2) Soluble in acetone. Practically insoluble
in water but will dissolve slowly as
hydrolysis takes place.
Stability: Stable at room temperature
Storage: Stored in well closed, light
resistant containers.
Use: Chronic myelogenous leukaemia
Brand: 1) Myleran
2) Busuphan 2 mg tab.

10. 4) Cisplatin
Physical properties:
1) Yellow colour crystalline powder
2) Less soluble in water
Stability: Unstable at room temperature
Storage: Stored at temperature 2-8 ⸰C
Use: Testicular and ovarian carcinoma.
Brand: 1) Cisplatin
2) Cisplat
3) Platinex
MOA: It is hydrolysed intracellularly to
produce a highly reactive moiety which causes
cross linking of DNA. The favoured site is N7
of guanine residue. It can also react with –SH
groups of cytoplasmic and nuclear proteins.
Cisplatin is a highly emetic drug. Antiemetics
are routinely administered before infusing it.
5) Methotrexate
Physical properties:
1) Yellow to orange-brown crystalline powder
2) Odourless
3) Practically insoluble in water and in alcohol.
Stability: Stable at room temperature.
Storage: Well closed light resistant containers.
Use: Non-Hodgkin lymphoma, breast, bladder, head and
neck cancers, osteogenic sarcoma, etc. It has prominent
immunosuppressant property useful in rheumatoid
arthritis, psoriasis and many other auto-immune disorders.
Brand: 1) Neotrexate 2.5 mg tab, 50 mg/2 ml inj.
2) Biotrexate 2.5 mg tab, 5, 15, 50 mg/vial inj.
MOA: Tetra-hydro-folic acid is an essential coenzyme
required for one carbon transfer reactions in de novo
purine synthesis and amino acid interconversions. Acts by
inhibiting dihydrofolate reductase (DHFRase)—blocking
the conversion of dihydrofolic acid (DHFA) to
tetrahydrofolic acid (THFA).
10 mg/10 ml,
50 mg/50 ml
vial.

11. 6) 5- Fluorouracil (5-FU)
Physical properties:
1) White crystalline powder
2) Odourless
3) Soluble in water and in alcohol.
4) Insoluble in chloroform, ether and benzene.
Stability: Stable when exposed to air.
Use: 1) Benign tumor of colon, rectum, stomach,
pancreas, liver, urinary bladder, head and neck.
2) Antifungal
3) Treatment of psoriasis.
Brand: 1) Fluracil
2) Five fluro
3) Fivocil
4) A 1% topical solution is also available.
7) Mercaptopurine (6- MP)
Physical properties:
1) Yellow crystalline powder
2) Odourless
3) Insoluble in water.
4) Soluble in alcohol, Dil. Alkali.
Stability: Stable
Use: 6-MP is especially useful in
childhood acute leukaemia,
choriocarcinoma and have been
employed in some solid tumours also.
Brand: 1) Purinethol
2) Empurine
3) 6- MP
250 mg/5 ml
500 mg/ 10 ml 50 mg tablet

12. 8) Azathioprine
➢It is a prodrug. Acts by getting converted to 6- MP.
➢It inhibits nucleotide conversions and de- novo purine synthesis.
➢This leads to inhibition of DNA, RNA and protein synthesis.
Physical properties:
1) Pale yellow crystals.
2) Slightly soluble in ethanol and chloroform.
3) Insoluble in water.
Stability: Stable at room temperature.
Storage: Well closed light resistant containers.
Use: Mostly used in autoimmune disease (Arthritis) and organ transplantation.
Brand: 1) Imuran
2) Transimune
3) Azoprine
50 mg tablets

13. ANTIBIOTICS USED AS ANTINEOPLASTICS
9) Actinomycin D (Dactinomycin)
➢ Very potent antineoplastic drug.
Physical properties:
1) Red crystalline powder / Yellow lyophilised
powder
2) Soluble in alcohol and water.
Stability: Sensitive to light. Should be protected from
heat and moisture. Solutions should not be exposed to
direct sunlight.
Storage: Stored in heat and light resistant container.
Use: 1) Wilms tumor
2) Methotrexate resistant carcinoma.
Brand: Dacmozen (0.5 mg / vial inj.)
MOA: Blocks RNA transcription by interfering with
template function of DNA.
It causes single strand breaks in DNA.
Intercalates between guanine- cytosine base pairs.
10) Daunorubicin (Rubidomycin)
It is an anthracycline antibiotic.
Physical properties:
1) Reddish needles.
2) Soluble in methanol and water.
Stability:
➢Powder used for reconstitution. No
bactericidal agent is added in solution used for
reconstitution. Thus, aseptic techniques are
strictly followed.
➢Reconstituted solution are protected from
sunlight.
➢Daunorubicin is unstable in solution. Its
decomposition is indicated by colour change
from red to blue- purple.
Use: Lymphoblastic leukaemia.
Brand: 1) Daunocin
2) Daunomycin
20 mg/ vial inj.