CHEMOTHERAPEUTIC AGENTS

PHARM.D 4th year(POST BACCULAUREATE).

 DEFINITION
 Cancer is a term used for diseases in which
abnormal cells divide without control and are
able to invade other tissues. Cancer cells can
spread to other parts of the body through the
blood and lymph systems.
 How cancer was developed &
spread?
 Cancerous cells develop from healthy cells in a complex
process called transformation.
 The first step in the process is initiation :

In which a change cells genetic material

(in the DNA and some times in the chromosome
structure) primes the cell to become cancerous.
o Cancer can occur by carcinogens include(chemicals ,
tobacco , viruses , radiation and sunlight) . A genetic
flaw in a cell may make it more susceptible. Even
chronic physical irritations may make a cell more
 The second and final step in the development of
cancer is called promotion.

 Unlike carcinogens promoters does not cause cancer

by them selves. But some carcinogens sufficiently
powerful to be able to cause cancer without the need
of promoters.
 Types of cancers
1) Leukemia's and lymphomas are cancers of blood
and blood forming tissues.
2) Carcinomas are cancers of epithelial cells which are
the cells cover the surface of body ,hormones and
glands.
 Eg: skin ,lungs ,stomach, breast, prostate and
thyroid gland cancer.
 Typically,carcinomas occur more often in older than
in younger people.
3) Sarcomas are cancers of mesodermal cells ,which
are the cells that form muscles and connective
tissue .
 Examples of sarcomas are

leiomyosarcoma (cancer of smooth muscle that is

found in the wall of digestive organs) and
osteosarcoma (bone cancer)
4) Central nervous system cancers - cancers that
begin in the tissues of the brain and spinal cord.
.
CELL CYCLE PHASES
 CHEMOTHERAPEUTIC AGENTS
 Chemotherapy utilizes chemicals that
interfere with the cell division process -
damaging proteins or DNA - so that cancer
cells will commit suicide. These treatments
target any rapidly dividing cells (not
necessarily just cancer cells), but normal cells
usually can recover from any chemical-
induced damage while cancer cells cannot.
 Chemotherapy is generally used to treat cancer that
has spread or metastasized because the medicines
travel throughout the entire body. It is a necessary
treatment for some forms of leukemia and
lymphoma.
 Chemotherapy treatment occurs in cycles so the
body has time to heal between doses.
 However, there are still common side effects such as
hair loss, nausea, fatigue, and vomiting.
Combination therapies often include multiple types
of chemotherapy or chemotherapy combined with
other treatment options.
 CHEMOTHERAPY DRUGS
Examples Mechanism of action Side Effects

Alkylating agents

Cyclophosphamide Form chemical bond with Suppress bone marrow

DNA, causing breaks in DNA Injure lining of stomach
Chlorambucil and errors in replication of Cause hair loss
DNA May decrease fertility
Melphalan Suppress the immune system
May cause leukemia
Antimetabolites
Methotrexate
Same as for alkylating agents
Cytarabine Block synthesis of DNA Do not increase risk of
leukemia
6- Mercaptopurine

5-Fluorouracil
 Examples Mechanism of action Side Effects

Antimitotics
Vincristine

Paclitaxel Same as for alkylating agents

Block division of cancer cells Also can cause nerve damage
Vinorelbine Do not cause leukemia

Docetaxel

Topoisomerase inhibitors Prevent DNA synthesis and Same as for alkylating agents
Doxorubicin repair through blockage of Doxorubicin
enzymes called can cause heart damage
Irinotecan topoisomerases

Platinum derivatives Form bonds with DNA causing Same as for alkylating agents
Cisplatin breaks Also can cause nerve and
kidney damage, hearing loss
Carboplatin

Oxaliplatin
 Examples Mechanism of action Side Effects

Hormonal therapies
Tamoxifen Blocks estrogen action (in Can cause endometrial cancer,
breast cancer) blood clots, hot flashes

Aromatase inhibitors
Bicalutamide Blocks androgen action (in Can cause erectile dysfunction
prostate cancer) (impotence) and diarrhea

Anastrozole Can cause bone loss

Exemestane Block estrogen formation (osteoporosis) and menopausal
Letrozole symptoms

Signaling inhibitors
Blocks signal for cell division in Can cause abnormal liver
Imatinib chronic myelocytic leukemia function test results and fluid
retention
 Examples Mechanism of action Side Effects

Gefitinib Blocks epidermal growth factor Can cause rash, diarrh

receptor
Erlotinib
Monoclonal antibodies
Rituximab Induces cell death through Can cause allergic reaction
binding to cell surface receptor
on lymphocyte-derived tumors
Trastuzumab
Blocks growth factor receptor on Can cause heart failure
breast cancer cells
Gemtuzumab
ozogamicin
Contains a specific antibody that Contains a specific antibody that
attaches to a receptor found on attaches to a receptor found on
leukemic cells and then delivers leukemic cells and then delivers
a toxic dose of its a toxic dose of its
chemotherapeutic component to chemotherapeutic component to
the leukemic cells the leukemic cells

Biologic response modifiers Can cause fever, chills, bone

Interferon-alpha Unknown marrow suppression, thyroid
deficiency, hepatitis
 Examples Mechanism of action Side Effects

Differentiating agents
Tretinoin Induces differentiation and
death of leukemic cells
Arsenic trioxide Induces differentiation and
death of leukemic cells
Can cause severe difficulty
with breathing (respiratory
distress)
Causes abnormal heart
rhythms and a rash

Agents that block blood

vessel formation
(antiangiogenic agents)
Bevacizumab Blocks vascular endothelial Can cause high blood
growth factor (VEGF) pressure, protein loss in
urine, bleeding, clotting,
intestinal perforation.

Serafinib Block VEGF receptor Can cause high blood

Sunitinib pressure and protein loss in
urine
 Combination Chemotherapy
Considerations
 Most cancers are/become refractory to treatment by a single agent,
combinations of anticancer drugs are often used. The following rules
apply to combining drugs in cancer chemotherapy:
1. The drugs each must have some activity against the cancer.
2. The drugs should act via different mechanisms.
3. The drugs should have minimal overlapping toxicity.
4. Cellular resistance to each drug should occur by different mechanisms.

  The first drug combination, made famous by Dr. V. DeVita and others at
NIH, is called MOPP (Mechlorethamine, oncovonin, procarbazine, and
prednisone). MOPP is a curative treatment for Hodgkin's disease and its
development was a major step forward
 CURRENT COMBINATIONS OF THERAPY
 ABVD: Doxorubicin (adriamycin), bleomycin, vinblastine,
dacarbazine –
 Used for: Hodgkin’s disease

 CHOP: Cyclophosphamide, doxorubicin (hydroxydaunorubicin),

vincristine (oncovin), prednisone – Used for: Non-Hodgkin's
lymphoma

 CMF: Cyclophosphamide, methotrexate, fluorouracil – Used for

Breast carcinoma

 IFL: Irinotecan, fluorouracil, leucovorin –

 Used for: Colorectal carcinoma with or without oxaliplatin

 MOPP: Mechlorethamine, vincristine (oncovin), procarbazine,

prednisone –
 Used for: Hodgkin’s disease

 PEB: Cisplatin (platinum), etoposide, bleomycin – Used for Testicular

carcinoma
 DRUG COMBINATIONS FOR MAJOR
CANCERS
 Carcinoma of lung:
› Cisplatin + taxane, or cisplatin + etoposide, or cisplatin +
irinotecan

 Carcinoma of breast:
› Hormonal therapy (Tamoxifen or Anastrozole)
› FAC: Fluorouracil, doxorubicin (adriamycin),
cyclophosphamide
› FEC: Fluorouracil, epirubicin, cyclophosphamide
› CMF: Cyclophosphamide, methotrexate, fluorouracil

 Carcinoma of prostate:
› Hormonal therapy: GnRH agonist plus androgen antagonist
 › Carcinoma of colon:

› IFL: Irinotecan, fluorouracil, leucovorin – with or

without oxaliplatin

› In trials: cisplatin, irinotecan, and a taxane

 Pedicatric Leukemia –

› Acute lymphocytic leukemia. Induction: vincristine plus

prednisone.
› Remission maintenance: mercaptopurine, methotrexate,
and cyclophosphamide in various combinations.

› Acute myelocytic and myelomonocytic leukemia.

Combination chemotherapy: cytarabine and mitoxantrone
COMPLICATIONS OF CHEMOTHERAPY
 SHORT TERM
Fever
Nausea
Infusional reactions
Oral complications
Diarrhea
Anemia
Neuropathy
Alopecia
Rash, Extravasation
Emotional
 Long-term :
› Cardiac
› Secondary Malignancies
› Fatigue
› Neuropathy
› Arthropathy
 References :

 http://www.cancer.gov/cancertopics/what-is-c
ancer
 www.medicalnewstoday.com/info/cancer.../
whatiscancer
 www.merckmanualonline.com .
THANK YOU