Chemotherapy of cancer

Chemotherapy of malignanCy
Balaji College of pharmaCy
mr.B.ChaKrapani m.pharm
aSSiStant profeSSor
pharmaCology&CliniCalpharmaColgy
Balaji College of pharmaCy
phone no :+91-9618279507
anticancer@rediffmail.com
anantapur.

ClaSSifiCation
1. ALKYLATINGAGENTS :
MECHLOROETHAMINE,
CYCLOPHOSPHAMIDE,
IFOSFAMIDE,
CHLOROAMBUCIL,
MELPHALAN,
THIOTEPA,
BUSULFAN,
CARMUSTINE,
STREPTOZOCOIN,
DACARBAZINE.

2.ANTIMETABOLITES
-FOLATE ANTAGONIST: METHOTREXATE
-PURINE ANTAGONIST: MERCAPTOPURINE,
THIOGUANINE,
PENTOSTAIN,
FLUDARABIINE,
CLADRIBINE.
PYRAMIDINE ANTAGONIST:
5-FLUROURACIL,
FLOXURIDINE,
CYTARBINE,
(CYTOSINE ARABINOSIDE) GEMCITABINE.

3.NATURAL PRODUTS:
ANTIBIOTICS:
ACTINOMYCIN-D(DACTINOMYCIN)
DAUNORUBICIN,
DOXORUBICIN,
BLEOMYCIN,
MITOMYCIN-C,
MITHRAMYCIN.
EPIPODOPHYLLOTOXINS:
ETOPOSIDE,
TENNIPOSIDE.

miSCellaneouS
PROCARBAZINE
MITOTANE
L-ASPARAGINASE
HYDROXYUREA
CISPLATIN
INTERFERON
ALPHA
IMATINIBS

SpeCifiC adverSe effeCtS of Some
antiCanCer drugS
DRUGS SPECIFICADVERSE
EFFECTS
OTHER PROMINENT
ADVERSE EFFECTS
CYCLOPHOSPHAMIDE CYSTITIS STOMATITIS BONE MARROW
DEPRESSION,ALOPECIA,V
OMITING,AMENORRHEA,T
ERATOGENICITY
BUSULFAN PULMONARY FIBROSIS
STOMATITIS
BONEMARROW
DEPRESSION,ALOPECIA,V
OMITING,AMENORRHEA,T
ERATOGENICITY.

SpeCifiC adverSe effeCtS of Some
antiCanCer drugS
DRUGS SPECIFICADVERSE
EFFECTS
OTHER PROMINENT
ADVERSE EFFECTS
CISPLATIN OTOTOXICITY RENAL DYSFUNCTION
BLEOMYCIN PULMONARY
FIBROSIS,EDEMA OF
HANDS.
STOMATITIS,ALOPECIA.
DAUNORUBICIN CARDIOTOXICITY,RED
CLOURED URINE
BONE MARROW
DEPRESSION,ALOPECIA.
DOXORUBICIN CARDIOTOXICITY BONE MARROW
DEPRESSION,ALOPECIA.
MITHRAMYCIN HEPATATOXICITY THROMBOCYTOPENIA

uSeS of alKylating agentS
ALKYLATING AGENTS USES
MECHLOROETHAMINE HODGKINS DISEASES
CYCLOPHOSPHAMIDE LYMPHOMAS AND LEUKEMIAS
IFOSFAMDE IMMUNOSUPPRESIVE AGENT
CHLOROAMBUCIL CHRONIC LYMPHOCYTIC LEUKEMIA
MELPHALAN MULTIPLE MYELOMA
BUSULPHAN CHRONIC MYELOID LEUKEMIA
CARMUSTIN MALIGNANT BRAIN TUMORS,
MELANOMA,LYMPHOMAS

CampotheCinS
Campothecin, analogs, topotecan and irinotecan
cause breaks in DNA leading to cell death .
Both are given intravenously.
Toxicity is milder and includes diarrhea and
bonemarrow suppression, nausea, weakness, and
skinrash.

CampotheCinS-1
Irinotecan inhibits the enzyme acetylcholinestrase
resulting in accumulation of acetylcholine causing
excessive salivation ,abdominal
cramps,miosis,bradycardia,and sweating which
respond to treatment with atropine.

hormoneS and their antagoniStS
GLUCOCORTICOIDS
ANDROGENS
ANTIANDROGENS
ESTROGENS
ANTIESTROGENS
PROGESTINS
AROMATASE INHIBITORS.

natural produCtS
CAMPTOTHECINS:
TOPOTECAN,
IRINOTECAN
TAXANES:
PACLITAXEL,
DOCETAXEL.
VINCAALKALOIDS:
VINCRISTINE,
VINBLASTINE,
VINORELBINE.

CanCer
Cancer is one of the major causes of death.
The treatment of cancers is still unsatisfactory due to
certain characteristics of the cancer cells.
Like capacity for uncontrolled proliferation,
Invasiness
Metastasis

Common adverSe effeCtS to
antiCanCer drugS
1.BONE MARROW DEPRESSION
2.OTHER PROLIFERATING CELLS.
3.IMMEDIATE ADVERSE EFFECTS.
4.TERATOGENECITY
5.CARCINOGENECITY

impliCationS
Correct dose should be determined and should be
double checked before administration.
Avoid direct contact of the anticancer drug with
skin and mucosa during preparation of the
formulation.
Monitor urine output.
Most anticancer drugs can cause vomiting .

Make sure antiemetics are given 30min before the
administration of such anticancer drugs.
Ensure that the patient is mentally prepared for hair
loss with chemotherapy.
Pregnant nurses should avoid handling anticancer
drugs.

With repeated cycles, patients would be
immunosuppresed ,so strict aseptic precautions are
to be taken.
Fever in immunosuppresed patient should be
reported immediately.
Take care to avoid extravasations of these drugs
because most of the anticancer drugs are irritants.

taxaneS
Paclitaxel was obtained from the bark of the western
yew tree .
It arrests cell division (Mitosis).
Paclitaxel is given intravenously.
It is metabolized in the liver.
Adverse effects include:
Myelosupression
Myalgia
Peripheral neuropathy
Docetaxel is more potent and orally effective.

taxaneS-1
Taxanes are useful in breast cancers and ovarian
cancers.
They are also found to be effective in the cancers of
the head and neck ,esophagus and lungs.

CanCer 1
A group of diseases characterized by abnormal
growth of cells .
To understand the effective of abnormal cells first u
have to know the function of healthy cells.
Each of us made up of millions of cells buliding
blocks of body cells make up of tissue ,tissue makes
up of organ.

CanCer-2
Healthy cells grows in a controlled way leaving in
a period & dying naturally, when the cells die the
body replaces with the another.
A set of instructions are located in the body dna
the each cell completes its life process.
Some time how ever mutation can occur in parts
of cell in dna the result will be very harmful the
cells which grows un controlled manner

CanCer-3
The initial mutation can occur from with in
the body penetrate in the body.
External factors :chemicals ,tobacco, radiation,
from the sun.
What ever the cause of dna mutation once it
occur can occurs cancer cells are often to
began and divide very rapid rate this can lead
to built of mass of cells known tumor.

CanCer -4
Some times tumors will be benign meaning
Other tumors are malignant (or) cancerous
actually they attract to blood ,because they
need blood & nutrients & oxygen supply
because the tumor has to grow.
Cancer become more serious when the cells
break away from malignant tumor &
metastasis & spread through blood stream (or)
lymphatic system , through distant organs.

CanCer -5
The lymphatic system is one of the body for
the first defense against diseases it includes ,
bone marrow, spleen,thymus,lymphnodes &
lymph vessels.
Cancer can be curable but it is most dangerous
second disease in the world.

CanCer 6
Researchers divide the causes of cancer into
two groups: those with an environmental cause
and those with a hereditary genetic cause.

neoplaSm
The term neoplasia means new growth’
New growth produced is called neoplasm (or)
tumor.
How ever all new growths or not neoplasm.
Since examples of new growth of tissues and cells
also exist in the process of embryogenesis,
regeneration and repair , hyper plasia and hormonal
stimulation .

definition of neoplaSm 1
Mass of tissue formed as a result of abnormal ,
excessive , un coordinated autonomous and
purposeless proliferation of cells.
Neoplasm may be benign when they are slow –
growing and localized with out causing much
difficulty to the host or malignant when they
proliferate rapidly , spread through out the body and
may eventually cause death of the host

epidemiologiC faCtorS of CanCer
A large number of pre disposing epidemiologic
factors or co –factors
Chronic non – neoplastic (pre-malignant) condition
Role of hormones in cancer

pre diSpoSing faCtorS
1. Familial and genetic factors
Retino Blastoma
Familial polyposis coli
Multiple endocrine neoplasia (MEN)
Neuro fibromatosis
Cancer of the breast
Dna –chromosomal in stability syndrome

CharaCteriStiCS of tumorS
1. Rate of growth
2. Clinical and gross features
3. Microscopic features
4. Local invasion(direct speed)
5. Metastasis (distant speed)

rate of growth
1. Rate of division and destruction of tumor cells
2. Degree of differentiation
I. Epidermal growth factor(EGF)
II. Fibroblast growth factor(FGF)
III.Platelet derived growth factor(PDGF)
IV.Colony stimulating factor(CSF)
V. Transforming growth factor(TGF)
VI.Interleukins (IL)

CliniCal & groSS featureS
The gross appearance
Benign tumors
Malignant tumors

environmental & Cultural faCtorS
1. Cigarette smoking
2. Alcohol abuse
3. Alcohol &tobacco together
4. Cancer of the cervix
5. Penile cancer
6. Betal nut cancer
7. Industrial & environmental substance
8. Certain constituents of the diet
9. Age
10.sex

diagnoSiS of CanCer
Histological method
Cytological method
Histochemistry & cyto chemistry
Immuno chemistry
Electron microscopy
Tumors makers (bio chemical assay)
Modern aids in tumor diagnosis
I. Flow cytometry
II.Insitu hybridisation
III.Molecular diagnostic technique
Analysis of molecular cytogeneic abuse

Cancers are classified by the type of cell that the
tumor resembles and is therefore presumed to be the
origin of the tumor. These types include:
Carcinoma: Cancer derived from epithelial cells. This
group includes many of the most common cancers,
including those of the breast, prostate, lung and colon.
Sarcoma: Cancer derived from connective tissue, or
mesenchymal cells.
ClaSSifiCation of CanCer

ClaSSifiCation of CanCer 1
Lymphoma and leukemia: Cancer derived from
hematopoietic (blood-forming) cells.
Germ cell tumor: Cancer derived from pluripotent
cells. In adults these are most often found in the
testicle and ovary, but are more common in babies and
young children.
 Blastoma: Cancer derived from immature
"precursor" or embryonic tissue. These are also
commonest in children

6-12 h
S G1
6-8 h
G2 M
3-4 h 1 h
Cell CyCle

Antineoplastic agents are used in an attempt
to destroy tumor cells by interfering with cellular
functions including replication.
Chemotherapy is used primarily to treat
systemic disease rather than localized lesions that
are amenable to surgery or radiation.

To understand how chemotherapy works as a treatment, it is helpful to
understand the normal life cycle of a cell in the body.
All living tissue is composed of cells. Cells grow and reproduce to
replace cells lost during injury or normal "wear and tear." The cell cycle
is a series of steps that both normal cells and cancer cells go through in
order to form new cells.
worKing

g1 phaSe
G1 Phase– This is the phase in which the cell
spends almost all of its time.
 It is the normal phase of the cell.
The cell is doing what ever that cell was
designed to do.
For example: a skin cell would function as a skin
cell during G1 and a liver cell would function as
a liver cell during G1.

S phaSe
S phase – the s phase is the phase during
which dna replication is occurring.
Out of sight of most people’s ability to see, the
dna is undergoing replication so, at the end
of the s phase, there would be two complete
sets of dna in the nucleus of that cell.
 In the s phase the cell has copied the contents
of its nucleus

g2 phaSe
 G2 Phase- In this phase, the cell makes copies of the important
organelles found in the cytoplasm.
 If a cell is going to divided, it needs enough mitochondria, (power
plants) endoplasmic reticulum, (highways) and so on to support itself
after cell division.
 If there are not enough mitochondria in one of the new cells, that cell
will die and the main purpose of cell division, to make two cells out of
one cell, will be for nothing.
 In G2 phase, the important organelles in the cytoplasm are copied to
ensure that the two new cells will have enough organelles each to
survive.

There are four parts to this phase;
1)PROPHASE,
2)METAPHASE,
3) ANAPHASE ,
4) TELOPHASE.
M Phase- This phase is the phase during
which the nucleus divides into two nuclei.
At the end of the M Phase, there will temporarily
be a single cell with two nuclei.

prophaSe
Prophase – Spindle fibers form, Chromosomes
shorten, thicken and become visible (under a
microscope) and the nuclear membrane begins
to dissolve.

METAPHASE
Spindle fibers move the chromosomes, which
have their copies wrapped around themselves, to
the middle of the nucleus and line them up.

ANAPHASE
Spindle fibers shorten and pull the identical
chromosomes away from each other to the
opposite side of the nucleus.

TELOPHASE
 Spindle fibers dissolve, chromosomes
lengthen out and become invisible again,
nuclear membrane reforms around both sets of
separated chromosomes.

CYTOKINESIS
The cytoplasm divides leaving you with two
identical cells, each with one nucleus.

HOdgKIN'S-dISEASE-SYMPTOMS
CYCLOPHOSPHAMIdE
MECHLOrOETHAMINE
Hodgkin's disease a disease with rubbery enlargement of lymph nodes and enlargement of spleen

HOdgKIN'S dISEASE-SYMPTOMS
drugS ArE uSEd :
CYCLOPHOSPHAMIdE
MECHLOrOETHAMINE
Hodgkin's disease a disease with
rubbery enlargement of lymph nodes
and enlargement of spleen.

HOdgKINS-dISEASE-SYMPTOMS
Hodgkin's disease a
disease with rubbery
enlargement of lymph
nodes and enlargement
of spleen.

LuNg CANCEr
Methotrexate –lung cancer
Mechanism of action
:Inhibits di hydrofolate
reduction blocks TMP and
Purine synthesis

Methotrexate –lung cancer
Mechanism of action :Inhibits di
hydrofolate reduction blocks TMP and
Purine synthesis

Flutamide –prostate cancer
Leuprolide-prostate cancer

WILMS TuMOr:
Malignant mixed tumor of the kidney seen
in children below fifth year

NEOPLASM :
Any abnormal new growth, tumor
benignant, not malignant

CErvICAL CANCEr
CISPLATIN –CErvICAL CANCEr

Second years II-I semester
Cancer of Buccal mucosa invading extra-oral tissues
following tobacco quid habit

Dr Suwas Darvekar
Cancer of Tongue following tobacco consumption

Dr Suwas Darvekar
Alveolar cancer after tobacco quid habit

NursiNg MaNageMeNt iN
CheMotherapy

Chemotherapy is a common treatment for a variety
of cancers.
It has proven to be safe and effective.
An understanding of this treatment helps patients
better recognize and tolerate side effects, if they occur

 Assess fluid and electrolyte status
(Anorexia, nausea & vomiting,
altered taste and diarrhea put
patient at risk)
 Modifying risk for infection and
bleeding
(suppression of the bone marrow
and immune system)
Administering Chemotherapy
patient is observed for extravasation
(particularly of vesicant agents,
which may produce necrosis if
deposited in subcutaneous tissues
Protect caregivers

Diarrhea can also be a side effect of chemotherapy. Caused
by the destruction of normal, dividing cells of the
gastrointestinal (GI) tract, diarrhea varies from patient to
patient. It is better managed if treated early
RENAL SYSTEM
Rapid tumor cell lysis- increased urinary excretion of uric
acid, which can cause renal damage
Myelosuppression- depression of bone marrow
function, resulting in decreased production of blood
cells.
-Decreases the number of RBCs (anemia), WBCs
(leukopenia) and platelets (thrombocytopenia)

Nausea & Vomiting- most common side
effects of chemotherapy and may persist for
as long as 24-48 hrs. after its administration.
Mucositis – inflammation of the mucosal
lining

It can cause irritation which can eventually lead to
inflammation of the mouth, a condition known as
stomatitis .
A stinging sensation in the throat may develop and
lead to dysphagia (difficulty in swallowing).
Management:
Good oral hygiene
gastroiNtestiNaL systeM

What are the side effeCts of
CheMotherapy?
SKIN
Alopecia
Hair loss occurs because
chemotherapy can sometimes
damage healthy cells.
It is so common because
hair follicle cells multiply
very quickly like cancer cells
and chemotherapy drugs have
difficulty in discerning the
difference.

sequeNCe of treatMeNts:
Adjuvant therapy: Therapy given after
surgery to reduce the likelihood of the cancer
returning.
Neo-adjuvant therapy: Therapy given before
surgery to shrink the tumor, allowing the
surgery to be more successful.
Concurrent therapy: When 2 or more
therapies are given together, such as
chemotherapy and radiation.

Orally (by mouth, in pill form)
Intravenously (IV, through a vein,
either as a short infusion or continuously
for one or more days)
As an injection or needle
Directly into a body cavity (i.e.: the
bladder, abdominal cavity)
Intra-arterially (in special cases, such
as limb perfusion treatment for
melanoma)
hoW is CheMotherapy giveN?

REPRODUCTIVE SYSTEM
 Take effective contraceptive precautions when
having chemotherapy, as the chemotherapy drugs
might harm the baby if pregnancy occurs.
In some women, chemotherapy brings on anIn some women, chemotherapy brings on an earlyearly
menopausemenopause. This may cause symptoms such as dryness. This may cause symptoms such as dryness
of the vagina and a decreased interest in sex.of the vagina and a decreased interest in sex.

NEUROLOGIC SYSTEM
•Peripheral neuropathies
•Loss of deep tendon reflexes
•Paralytic ileus
MISCELLANEOUS
•Fatigue
•Alopecia

Chemotherapy of cancer

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