Chemotherapy uses cytotoxic drugs to treat cancer by interfering with cancer cell replication and metabolism. There are several classes of chemotherapy drugs including alkylating agents, antimetabolites, antitumor antibiotics, mitotic inhibitors, hormones and antagonists, and miscellaneous agents. Chemotherapy can be used adjuvantly after surgery or neoadjuvantly before surgery or radiation to destroy micrometastases or reduce tumor size. Common side effects include nausea, vomiting, bone marrow depression, alopecia, and organ toxicity.

2. Chemotherapy
Chemotherapy involves the use of cytotoxic
medications to cure cancer or decrease tumor
size or to prevent or treat suspected
metastases.
It interfering with the ability of the malignant
cell to synthesize vital enzymes and
chemicals.

3. • Chemotherapy disrupts the cell cycle in
various phases by interrupting cell
metabolism and replication.
• Based on the chemical makeup and
biological activity, different drugs used for
cancer treatment act in specific phases and
sub phases of the cell cycle.

4. Adjuvant & Neoadjuvant
chemotherapy
• Adjuvant chemotherapy:
– Chemotherapy given after surgery or irradiation
to destroy micrometastasis & prevent
development of secondary neoplasm.
• Neo-adjuvant chemotherapy:
– Chemotherapy given before surgery or
radiotherapy in order to diminish the volume of
large primary neoplasm

5. • Nausea & Vomiting
• Bone marrow depression
• Alopecia
• Gonads: Oligospermia, impotence, ↓ ovulation
• Foetus: Abortion, foetal death, teratogenicity
• Carcinogenicity
• Hyperuricemia
• Immunosupression: Fludarabine
General toxicity of cytotoxic drugs

6. Classes of chemotherapy drugs
Chemotherapeutic agents can be classified
either by the effects of the agent on the cell or
by the pharmacological properties of the
agent.
• Chemotherapeutic agents can be divided
into
– Cell cycle-specific
– Cell cycle - nonspecific agents.

7. Cell cycle-specific
• These are the agents effective at a specific
phase (e.g. S and M phases) in the cell cycle
to prevent cell replication by damaging
cellular DNA and blocking production of
protein necessary for DNA and RNA
synthesis.

8. Cell cycle-nonspecific
• These are the agents effective throughout all
the phases of the cell cycle, including the
resting phase.

10. Chemotherapeutic agents are classified based
on pharmacological properties of the agent.
The classifications include
a. Alkylating agents
b. Antimetabolites
c. Antitumour antibiotics
d. Mitotic inhibitors
e. Hormones and hormone antagonists
f. Miscellaneous agents

11. Alkylating agents
• Alkylating agents are not phase specific and
basically act on preformed nucleic acids by
creating defects in tumor DNA. They cause
crosslinking of DNA strands and interfere with
replication and transcription.
• It acts with proliferating and non proliferating
cells those in G0 phase.

12. The several subclasses of alkylating agents include
– Nitrogen Mustards
• Meclorethamine, Melphalan, Chlorambucil,
cyclophosphamide, ifosfamide
– Ethyleneimine : Thiotepa
– Alkyl Sulfonate: Busulfan
– Nitrosureas
• Carmustine,lomustine, streptozocin
– Triazines
• Dacarbazine, temozolamide

13. Antimetabolites
• Antimetabolites are phase specific, working
best in the S phase and having little effect in
G0. It interfere with nucleic acid synthesis by
displacing metabolites at the regulatory site
of a key enzyme.

14. Classifications of antimetabolites
• Folate Antagonists
– Methotrexate
• Purine Antagonists
– 6 Mercaptopurine, 6 Thioguanine, Azathioprine
• Pyrimidine antagonists
– 5 Fluorouracil, cytarabine, gemcitabine

15. Antitumour antibiotics
• Antitumour antibiotics derived from natural
sources that are generally too toxic to be
used as anti - bacterial agents.
• They are not phase specific and act in
several ways: they disrupt DNA replication
and RNA transcription; create free radicals,
which generate breaks in DNA and other
forms of damage; and interfere with DNA
repair.

16. • These antibiotics include
– Actinomycin D
– Doxorubicin
– Bleomycin
– Mitomycin-C
– Mithramycin.

17. Mitotic inhibitors
• Mitotic inhibitors are drugs that act to prevent cell division
during the M phase. Mitotic inhibitors include the plant
alkaloids and taxoids.
– Plant alkaloids consist of medications extracted from
plant sources (periwinkle plant) : Vinca alkaloids (e.g.
vincristine and vinblastine) and etoposide.
– The taxoids act during the
G2 phase to inhibit cell division.
Example:
• Paclitaxel
• Docetaxel

18. Hormones and antagonists
• The main hormones used in cancer therapy
are the corticosteroids which are phase
specific (G1).
• These act by binding to specific intracellular
receptors, repressing transcription of mRNA
and thereby altering cellular function and
growth.

19. Hormone antagonists
• Hormone antagonists work with hormone-
binding tumors. They block the hormone’s
receptor site on the tumor and prevent it
from receiving normal hormonal growth
stimulation.
• Examples of Hormone, Hormone antagonists
are

20. • Corticosteroids
– Prednisolone
• Estrogens
– Ethinyl Estradiol
• Selective Oestrogen
Receptor Modulator (SERM)
– Tamoxifene
– Toremifene
• Selective Oestrogen
Receptor Degrader (SERD)
– Fulvestrant
• Aromatase Inhibitors
– Letrozole
– Anastrazole
– Exemestane
• Progestins
– Hydroxyprogesterone
• Anti-androgens
– Flutamide
– Bicalutamide
• 5- reductase Inhibitors
– Finasteride
– Dutasteride
• GnRH analogs
– Naferelin
– Goserelin
– Leuoprolide
Natural Products

21. • Enzymes
• L-asparginase
• Epipodophyllotoxins
–Etoposide, tenoposide
• Camptothecin analogs
–Topotecan, irinotecan
• Biological response modifiers
– Interferons
– Interleukins

22. Miscellaneous agents
• Several miscellaneous agents act at different
phases in the cell cycle.
–Cisplatin
–Carboplatin
–Hydroxurea
–Procarbazine
–Mitotane
–Imatinib

23. Newer anticancer drugs
• Inhibitors of growth factors receptors
– Imatinib: CML (BCR-ABL gene)
– Gefitinib: Non small cell cancer of lungs (EGFR)
– Nilotinib : CML (Tyrosine kinase inhibitor)
– Dasatinib : CML (Tyrosine kinase inhibitor)
– Lapatinib : metastatic breast cancer (HER2/neu)
– Sunitinib : renal cell carcinoma (VEGF)
– Sorafinib : renal cell carcinoma (VEGF)

24. • Monoclonal antibodies
– Trastuzumab : breast cancer (HER2/neu)
– Bevacizumab: metastatic colon cancer (VEGF)
– Rituximab : non hodgkins lymphoma (CD-20)
– Panitumumab : metastatic colon cancer (EGFR)
– Alemtuzumab : CLL (CD 52 antigen)
– Iodine tositumonab : Non hodgkins (CD-20)