Drugs used in cancer.pptm

DRUGS USED IN
CANCER
Submitted to –Dr. Kamna Srivastava
Submitted by –Devinder Yadav.M.Sc II year

Some Definitions :
• Cancer is the rapid creation of abnormal cells that grow beyond their usual
boundaries, and which can then invade adjoining parts of the body and
spread to other organs. This process is referred to as metastasis.
Metastases are the major cause of death from cancer. (WHO)
Cancer known medically as a malignant neoplasm, is a broad group of
diseases involving unregulated cell growth. In cancer, cells divide and grow
uncontrollably, forming malignant tumors, and invading nearby parts of the
body. The cancer may also spread to more distant parts of the body through
the lymphatic system or bloodstream. Not all tumors are cancerous; benign
tumors do not invade neighboring tissues and do not spread throughout the
body. There are over 200 different known cancers that affect humans.

Risk factor associated with cancer
1.Tobacco
2.Sunlight
3.Ionizing radiation
4.Certain chemicals and other substances
5.Some viruses and bacteria
6.Certain hormones
7.Family history of cancer
8.Alcohol
9.Poor diet, lack of physical activity, or being overweight

Characteristics of cancer:
⮚Cancer arises as a result of a series of genetic and epigenetic changes, the main genetic lesions being:
• inactivation of tumor suppressor genes
• the activation of oncogenes (mutation of the normal genes controlling cell division and other
processes)
⮚Cancer cells have four characteristics that distinguish them from
normal cells:
• uncontrolled proliferation
• loss of function because of lack of capacity to differentiate
• invasiveness
• the ability to metastasis.
⮚Cancer cells have uncontrolled proliferation because of changes in:
• growth factors and/or their receptors
• intracellular signalling pathways, particularly those controlling the cell cycle and apoptosis
• telomerase expression
• tumour-related angiogenesis

THE SEVEN WARNING SIGNS OF CANCER
The American Cancer Society uses the word C-A-U-T-IO-N to help
recognize the seven early signs of cancer:
1.Change in bowel or bladder habits
2.A sore that does not heal
3.Unusual bleeding or discharge
4.Thickening or lump in the breast, testicles, or elsewhere
5.Indigestion or difficulty swallowing
6.Obvious change in the size, color, shape, or thickness of a wart, mole, or
mouth sore
7.Nagging cough or hoarseness

CANCER TYPES :
categorized based on the functions/locations of the cells from which they
originate:
• Carcinoma: a tumor derived from epithelial cells, those cells that line
the surface of our skin and organs (80-90% of all cancer cases reported)
• Sarcoma: a tumor derived from muscle, bone, cartilage, fat or
connective tissues.
• Leukemia: a cancer derived from white blood cells or their precursors.
• Lymphoma: a cancer of bone marrow derived cells that affects the
system.
• Myelomas: a cancer involving the white blood cells responsible for the
production of antibodies (B lymphocytes)

Normal Cell
DNA Damage
Mutations in the genome of
somatic cells
Inactivation of cancer
suppressor genes
Activation of growth
promoting oncogene
Alteration of genes that
regulates apoptosis
•Clonal expansion
•Additional mutations
•Heterogeneity
Expression of altered gene products
Loss of regulatory gene product
MALIGNANT NEOPLASM
Acquired
(environmental
DNA damaging
agents)
Chemicals
Radiation
viruses
Successful DNA repair
Failure of DNA repair
Carcinogenesis

TREATMENT OPTIONS OF CANCER
1. Surgery:
before 1955
2.Radiotherapy:
1955~1965
3.Chemotherapy:
after 1965
4.Immunotherapy
5. Gene therapy

How is Cancer Diagnosed & Staged ?
• Common test include the following:
• Biopsy - involves histological examination by a pathologist of a piece of tissue.
Extracting cancer cells & looking at them under a microscope is the absolute way
to diagnose cancer . This procedure is called Biopsy . Physicians will analyze your
body sugar ,fats , proteins, and DNA at the molecular level.
• Laboratory test- Blood test (which looks for chemicals such as tumor markers
Example:CA15-3 - Breast cancer. ;CA19-9 - Gastrointestinal tumours ;CA-125 -
Ovarian cancers ;PSA - Prostate cancers.
• Bone marrow biopsy
• Complete blood count (CBC)
• Imaging techniques –CT scan, MRI,UTZ

ANTI CANCER DRUG CLASSIFICATION WITH CLASS
TYPE

Mechanisms and sites of action of some of the drugs
used in the treatment of cancer.

Alkylating agent :
Alkylating agents contain chemical groups that produce highly reactive carbonium
ion intermediates that can form covalent bonds with particular nucleophilic,
substances in the cell.
b. These ions are highly reactive with electron donors such as amine, hydroxy and
sulfhydryl groups.
c. The nitrogen at position 7(N7) of guanine residues in DNA is strongly nucleophilic
and is especially susceptible. other molecular sites such as N1 and N3 of adenine
and N3 of cytosine may also be effected.
d. Most of the alkylating agents are bifunctional (have two alkylating groups) and
are able to react with two groups causing intra or inter chain cross linking.
e. This can interfere not only with transcription but also with replication. Thus
alkylation may result in cross linking, cross scission or abnormal base pairing.
f. Alkylating agents mainly exert cytotoxic actions. some of alkylating agents have
CNS stimulant, immuno suppressant and cholinergic properties.

(N7) position of
guanine residues
With nitrogen mustard

Ethylenimine
-Thio-TEPA
Triazine
- Dacarbazine
Mechlorethamines
( Nitrogen mustard )
-Cyclophosphamide
-Ifosfamide
-Chlorambucil
- Melphalan
Alkyl sulfonate
- Busulfan
Nitrosoureas
-Carmustine
-Lomustine
Major
classes of
Alkylating
agents
Platinum coordination
complexes
- Cis -platin
-carboplatin
-oxaliplatin

Nitrogen mustard
• Mechlorethamine , a bifunctional alkylating agents , interferes with
DNA replication and RNA transcription as the result of formation of
unstable carbonium ions which form interstand cross – links with
DNA , likely binding at the N7 position of guanine . Mechlorethamine
has weak immunosuppressive properties . Mechlorethamine is a cell
cycle phase non-specific , however ,its effect is most pronounced in
the S phase , and cell proliferation is arrested in G2 phase . Topical
acrivity of mechlorethamine may also involve immune mechanisms.

Mechlorethamines ( Nitrogen mustard )
• Mechlorethamine is alkylates the N7
nitrogen of a guanine residue in one or
both strands of a DNA molecule This
alkylation leads to cross-linkages between
guanine residues in the DNA chains and/or
depurination, thus facilitating DNA strand
breakage.
• Alkylation can also cause miscoding
mutations.

No
.
name
1 Cyclophosp-
hamide
Cytoxan®
or
Neosar®
Hodgkin’s and non-Hodgkin’s lymphoma,
Burkitt’s lymphoma, chronic lymphocytic
leukemia, chronic myelocytic leukemia, acute
myelocytic leukemia, acute lymphocytic
leukemia, t-cell lymphoma, multiple myeloma,
neuroblastoma, retinoblastoma,
rhabdomyosarcoma, Ewing’s sarcoma; breast,
testicular, endometrial, ovarian, and lung
cancers
by intravenous injection or
mouth in the form of tablet,
intramuscular .
2 Mechloreth-
amine
Mustargen
®
Hodgkin’s disease and non-Hodgkin’s lymphoma,
and as a palliative therapy for breast and lung
cancers, and as a topical treatment for skin
lesions of mycosis fungoides (cutaneous T-cell
lymphoma).
By injection
3 Ifosfamide Ifex® Hodgkin’s and non-Hodgkin’s lymphoma, as well
as recurrent testicular cancer and germ cell
tumors, sarcomas, lung cancer, bladder cancer,
head and neck cancer, and cervical cancer.
4 Melphalan Alkeran® multiple myeloma, ovarian cancer,
neuroblastoma, rhabdomyosarcoma, and breast
cancer
Intravenous
5 chlorambucil Leukeran® chronic lymphocytic leukemia, malignant
lymphomas including lymphosarcoma, giant
follicular lymphoma, and Hodgkin’s disease. non-
Hodgkin’s lymphoma, breast, ovarian and
testicular cancer, Waldenstrom’s
macroglobulinemia, thrombocythemia, and
Tablet form
Moderate depression of peripheral
blood count; excessive doses
produce
severe bone marrow depression with
leukopenia, thrombocytopenia, and
bleeding; alopecia and hemorrhagic
cystitis occasionally occur with
cyclophosphamide; cystitis can be
prevented with adequate hydration;
busulfan is associated
with skin pigmentation, pulmonary
fibrosis, and adrenal insufficiency .
Nausea and
vomiting

Nitrosoureas
• The nitrosoureas have an important role in the treatment of brain
tumors and find occasional use in treating lymphomas and in high-
dose regimens with bone marrow reconstitution. They function as
bifunctional alkylating agents but differ from conventional nitrogen
mustards in both pharmacological and toxicological properties.
Carmustine (BCNU) and lomustine (CCNU) are highly lipophilic and
thus readily cross the blood-brain barrier, an important property in
the treatment of brain tumors. As with other alkylating agents, the
nitrosoureas are highly carcinogenic and mutagenic.

Sr
No.
Drug
name
Market
name
Used for route of
administration
1 streptozocin Zanosar®, islet cell pancreatic cancer by intravenous
2 Carmustine BiCNU® or
BCNU
brain tumors, glioblastoma, brainstem
glioma, medulloblastoma, astrocytoma,
ependymoma, and metastatic brain
tumors.multiple myeloma, Hodgkin’s
disease, non-Hodgkin’s lymphoma,
melanoma, lung cancer, and colon cancer.
Intravenously
3 Lomustine CCNU or
CeeNU®
primary and metastatic brain tumors,
Hodgkin’s disease and non-Hodgkin’s
lymphoma, and has also been used for
melanoma, lung, and colon cancer
Capsules (10mg, 40
mg and 100mg ) take
this drug with empty
stomach .
The word nitrosurea refers to the molecule’s nitroso (R-NO) group and carmamide
(or urea) group CO(NH2)2. These drugs are lipophilic and are able to cross
the blood-brain barrier. That’s why there are sometimes used to treat
brain cancer
Nitrosoureas:
Adverse effects :
Nausea and
vomiting
Myelosuppression;
rarely interstitial lung
disease and interstitial
nephritis.
Nausea and
vomiting

1 Thiotepa Thioplex® breast cancer, ovarian cancer,
Hodgkin’s disease, and non-
Hodgkin’s lymphoma.
Intravenous
infusion
2 Altretamine Hexalen® treat ovarian cancer given in pill
form and
should be
taken after
meal
Ethylenimines
Although nitrogen mustards containing chloroethyl groups constitute the most widely used class of alkylating agents, other
alkylators such as ethyleneimines with greater chemical stability and well -defined activity in specific types of cancer have
value in clinical practice.
These are derived from ethylenimine, which is a three-pointed ring of two carbon atoms and a nitrogen
atom. Ethylenimine is also called aziridine
Sr No. Drug name Market name Used for route of administration
Adverse effects :
Nausea and
Vomiting
adverse effects :
Nausea and
vomiting
Myelosuppression,
peripheral neuropathy,
flu-like syndrome

Dacarbazine DTIC-Dome® metastatic malignant melanoma,
Hodgkin’s disease, soft tissue
sarcomas, neuroblastoma,
fibrosarcomas,
rhabdomyosarcoma, islet cell
carcinoma, and medullary thyroid
carcinoma.
Intravenously
Temozolomi
de
Temodar® brain tumors anaplastic
astrocytoma and glioblastoma
multiforme
Pills (5mg, 20 mg and
100mg and 250 mg )
. Drug name Market name Used for route of administration adverse effects
Triazines
Triazines are aromatic compounds with rings of carbon and nitrogen.
Nausea and vomiting
Myelosuppression, central nervous
system toxicity with neuropathy,
ataxia,lethargy, and confusion.
Nausea and
vomiting, headache
and fatigue Myelosuppression, mild
elevation in liver function tests,
photosensitivity

Sr No. Drug name Market name Used for route of dose
1 Busulfan Busulfex® and
Myleran®
chronic myelogenous
leukemia
by intravenous , pill form
Alkyl Sulfonates
Adverse effects : Nausea and vomiting
Busulfan exerts few pharmacological actions other than myelosuppression at
conventional doses and, prior to the advent of imatinib mesylate, was a standard agent
for patients in the chronic phase of myelocytic leukemia and caused a severe and
prolonged pancytopenia in some patients. Busulfan now is primarily used in high-dose
regimens, in which pulmonary fibrosis, GI mucosal damage, and hepatic VOD are
important toxicities.

Platinum coordination complexes
• Platinum coordination complexes have broad antineoplastic activity
and have become the foundation for treatment of ovarian, head and
neck, bladder, esophagus, lung, and colon cancers. Although cisplatin
and other platinum complexes do not form carbonium ion
intermediates like other alkylating agents or formally alkylate DNA,
they covalently bind to nucleophilic sites on DNA and share many
pharmacological attributes with alkylators.

Cis -platin Mechanism of Action

Mechanism of Action
Aquation of cisplatin is favored at the low concentrations of Cl– inside the
cell and in the urine. High concentrations of Cl– stabilize the drug, explaining
the effectiveness of Cl– diuresis in preventing nephrotoxicity. The activated
platinum complexes can react with electron-rich regions, such as
sulfhydryls, and with various sites on DNA, forming both intrastrand and
interstrand cross-links. The DNA-platinum adducts inhibit replication and
transcription, lead to single- and double-stranded breaks and miscoding,
and if recognized by p53 and other checkpoint proteins, cause induction of
apoptosis. Adduct formation is an important predictor of clinical response
.The analogues differ in the conformation of their adducts and the effects of
adduct on DNA structure and function. Oxaliplatin and carboplatin are
slower to form adducts. The oxaliplatin adducts are bulkier and less readily
repaired, create a different pattern of distortion of the DNA helix, and differ
from cisplatin adducts in the pattern of hydrogen bonding to adjacent
segments of DNA

Therapeutic uses of platinum coordination
complexes
• Cisplatin, in combination with bleomycin, etoposide, or with ifosfamide
and vinblastine, cures 90% of patients with testicular cancer.
• Cisplatin produces responses in cancers of the bladder, head and neck,
cervix, and endometrium; all forms of carcinoma of the lung; anal and
rectal carcinomas; and neoplasms of childhood. The drug also sensitizes
cells to radiation therapy and enhances control of locally advanced lung,
esophageal, and head and neck tumors when given with irradiation.
• Cisplatin is given only intravenously. To prevent renal toxicity, it is
important to establish a chloride diuresis by the infusion of 1–2 L of normal
saline prior to treatment.

Side effects :
- The following side effects are common (occurring in greater than 30%) for patients taking Cisplatin:
• Nausea and vomiting. Nausea may last up to 1 week after therapy. Anti-nausea medication is given before the infusion, and a
prescription is also given for use after.
• Low blood counts. white and red blood cells and platelets may temporarily decrease. This can put you at increased risk for
infection, anemia, and/or bleeding. Kidney toxicity. Effects on kidney function are dose related, observed 10-20 days after
therapy, and are generally reversible.
• Ototoxicity hearing loss, ringing in the ears.
• Blood test abnormalities (low magnesium, low calcium, low potassium)
-These are less common side effects (occurring in 10-29%) for patients receiving Cisplatin:
• Peripheral neuropathy: Although less common, a serious side effect of decreased sensation and paresthesia (numbness and
tingling of the extremities) may be noted. Sensory loss, numbness and tingling, and difficulty in walking may last for at least
as long as therapy is continued. These side effects may become progressively more severe with continued treatment, and
your doctor may decide to decrease your dose. Neurologic effects may be irreversible.
• Loss of appetite
• Taste changes, metallic taste
• Increases in blood tests measuring liver function. These return to normal once treatment is discontinued (see liver problems).
• Hair loss may cause hair loss; however, this side effect is uncommon

ANTIMETABOLITES
• Antimetabolites are structurally related to normal component of DNA
or of coenzymes involved in the nucleic acid synthesis. These
generally interfere with the availability of purine or pyrimidine
nucleotide precursors by inhibiting their synthesis or by competing
with them in DNA or RNA synthesis.
• Anti metabolites inhibit nucleic acid synthesis by Competitive
inhibition of cellular components . They achieve this by combining
with specific enzymes or getting incorporated into specific enzymes
thereby forming inactive macromolecules and consequences cell
death .They act specific phase of cell cycle .
• Examples: 5 Fluorouracil, 6-Mercaptopurine ,Methotrexate .

Purine Inhibitors & related
inhibitors
-Mercapopurine
(6-Mercaptipurine,6-MP)
-Pentostatin(2”deoxyformycin)
- Cladribine ,fludarabine
Folic Acid Analogs
Methotrexate(amethopterin)
-Pemetrexed
Pyrimidine Analogs
-Fluorouracil(5- fluorocil,5-FU)
-Capacitabine
-Cytarabine (cytosine arabinoside
ANTIMETABOLITES

Antimetabolites: sites of drug action

METHOTREXATE
• Methotrexate is the most widely used antimetabolite in cancer
chemotherapy .
a. It mainly acts by inhibiting the enzyme dihydro folate reductase
(DHFR),which is essential in synthesis of folate.
b. It is cell cycle specific and kills cells in S phase.
c. It mainly inhibits the synthesis of DNA also affects RNA and protein
synthesis.

1.folic acid is essential for the production of
coenzyme,tetrahydrofolic acid(THF).
2. The conversion of folate to THF is carried
out by an enzyme, Dihydrofolate reductase.
3. Methotrexate competes with folic acid for
this enzyme by binding irreversibly to
Dihydrofolate reductase , thus inhibiting the
production of THF.
4. lack of the co-enzyme THF leads to
inhibition of DNA synthesis and consequently
of cell replication.
FH2 = dihydrofolate; FH4 = tetrahydrofolate; dTMP =
deoxythymidine monophosphate;
MECHANISM OF ACTION :

• PHARMACOKINETICS
• 1.Methotrexate is usually administered orally.it can also be given intramuscularly,
intravenously. Methotrexate is readily absorbed from the GI tract at doses of less than 25
mg/m2;
2.The drug is mainly concentrated in intestinal epithelium, liver,kidney,skin.
3. It is actively taken up by the cells and is metabolized into polyglutamate
derivatives, which are retained in cells for long time.
• ADVERSE EFFECTS
1.Unwanted effects are due to deficiency of folate and include depression
of bone marrow and damage to gastrointestinal epithelium.
2. Other unwanted effects include pneumonitis, nephrotoxicity,pulmonary
toxicity and neurologic toxicity, high doses produce pancytopenia .
USES:
1. Provide great benefit to patirnts suffering with Leukaemia & Acute Myeloid Leukaemia
osteosarcoma& head ,neck and breast cancer .
2. lung cancer.
3. psoriasis.

MECHANISM OF ACTION OF 6-
MERCAPTOPURINE⮚6-Mercaptopurine penetrates target
cells and be converted to the
ribonucleotide of 6-mercaptopurine.
which is a purine nucleotide analog.
⮚This leads to inhibit the first step of
denovo purine-ring biosynthesis.
⮚This results in nonfunctional RNA and
DNA.
.

PHARMACOKINETICS
1. The drug is well absorbed on oral administration
. PHARMACOKINETICS
1. The drug is well absorbed on oral administration.
2. It is distributed well throughout the body except cerebrospinal fluid.
3. It is metabolized to thiouric acid by xanthine oxidase.
4. Mercaptopurine and its metabolites are rapidly excreted by the kidney.
ADVERSE EFFECTS
1.Unwanted effects include nausea,vomiting,diarrhoea.
2. Bone marrow depression is the main toxic effect produced and hepatotoxicity
is also reported.
CLINICAL USES
6-mercoptopurine is mainly used in childhood acute leukaemia, choriocarcinoma
and in solid tumours.
It is also used in the maintenance of remission in acute lymphoblastic leukaemia.
3. It is metabolized to thiouric acid by xanthine oxidase.

MECHANISM OF ACTION OF 5-
FLUOROURACIL
⮚5-Fluorouracil is an analogue of uracil
(pyrimidine).
⮚It must be converted in the body to the
corresponding deoxynucleotide (5-fluoro-2-
deoxy uridine monophosphate),which
inhibits thymidylate synthesis and blocks the
conversion of deoxyuridilic acid to
deoxythymidilic acid and reduce the
thymidine.
⮚ DNA synthesis decreases due to lack
of thymidine, leading to imbalanced cell growth
5-FU = 5-fluorouracil; 5-FUR = 5-fluorouridine; 5-FUMP = 5-
fluorouridine
monophosphate; 5-FUDP = 5-fluorouridine diphosphate; 5-
FUTP = 5-fluorouridine
triphosphate; dUMP = deoxyuridine monophosphate; dTMP =
deoxythymidine
monophosphate. 5-FdUMP = 5-fluorodeoxyuridine
monophosphate.

PHARMACOKINETICS :
. 5-Fluorouracil is administered intravenously to prevent first-pass metabolism.
. It is well distributed in the body including CNS.
. It is mainly metabolized in liver and dosage must be adjusted in impaired hepatic function.
ADVERSE EFFECTS
. Unwanted effects include gastrointestinal disturbances.
. ulcers in GIT.
. Bone marrow depression and anorexia,anaemia, blurred vision , pigmentation of skin ,
dermatitis , hair thining.
5 Flurouracil is used for treating the following cancers
⮚ Breast cancer
⮚ Liver
⮚ Skin cancer
⮚ Stomach ,pancreatic cancer, colon & rectal cancer
Cancer of anus .cervix , endometrium ,prostate, ovaries
5Fluass metabolism.
. It is well distributed in the body including CNS.
. It is mainly metabolized in liver and dosage must be

ANTIBIOTICS
The recognition of antibiotics as an important class of neoplastic agents is quite
recent .
Screening of microbial products led to the discovery of a number of growth-
inhibiting compounds that have proved to be clinically useful in cancer
chemotherapy. Many of these antibiotics bind to DNA through intercalation
between specific bases and block the synthesis of RNA, DNA, or both; cause DNA
strand scission; and interfere with cell replication. All of the anti-cancer antibiotics
now being used in clinical practice are products of various strains of the soil
microbe Streptomyces.
Consequently ,the production of antineoplastic agents through proper strain
selection and controlled microbial fermentation conditions may ultimately
optimize the formation of a particular component in an antibiotic mixture .
A few important members of this category are described below namely :
Dactinomycin, Daunomycin, Bleomycin etc.

Anthracycline
• The anthracycline antibiotics, isolated from Streptomyces peucetius var caesius, are
among the most widely used cytotoxic anti-cancer drugs. The structures of the two
original anthracyclines, doxorubicin and daunorubicin, are shown below. Several
other anthracycline analogs have entered clinical practice, including idarubicin,
epirubicin, and mitoxantrone. The anthracyclines exert their cytotoxic action through
four major mechanisms:
(1) inhibition of topoisomerase II
(2) generation of semiquinone free radicals and oxygen free radicals through an iron
dependent, enzyme-mediated reductive process;
(3) high-affinity binding to DNA through intercalation, with consequent blockade of the
synthesis of DNA and RNA, and DNA strand scission; and
(4) binding to cellular membranes to alter fluidity and ion transport. While the precise
mechanisms by which the anthracyclines exert their cytotoxic effects remain to be
defined in particular tumors, the free radical mechanism is well-established to be the
cause of the cardiotoxicity associated with the anthracyclines.

MECHANISM OF ACTION OF DOXORUBICIN AND DAUNORUBICIN
• Doxorubicin and daunorubicin
bind to the sugar phosphate
backbone of DNA. This causes
local uncoiling ,which leads to
blocks DNA & RNA synthesis and
catalyzed breakage supercoiled
DNA strand, causing irreparable
breaks.
• Catalyzes the reduction of free
radicals. These in turn reduce
molecular O2, producing
superoxide ions and hydrogen
peroxide, which mediate single
strand scission of DNA

Actinomycin-D
• Actinomycin D is very potent antineoplastic antibiotic obtained from
the species of Streptomyces. Actinomycin D has beneficial effects in
the treatment of solid tumors in children and choriocarcinoma in
adult women.
• MECHANISM OF ACTION
The drug intercalates into the minor groove of double helix between
guanine-cytosine base pairs of DNA and interfere with the movement
of RNA polymerase along the gene and thus preventing transcription.
It may also cause strand breaks and stabilize DNA topoisomerase
II complex.

Mechanism of Action
The capacity of actinomycins to bind to double-
helical DNA is responsible for their biological
activity and cytotoxicity. The planar
phenoxazone ring intercalates between
adjacent guanine-cytosine base pairs of DNA,
while the polypeptide chains extend along the
minor groove of the helix, resulting in a
dactinomycin-DNA complex with stability
sufficient to block the transcription of DNA by
RNA polymerase. The DNA-dependent RNA
polymerases are much more sensitive to the
effects of dactinomycin than are the DNA
polymerases. In addition, dactinomycin causes
single-strand breaks in DNA, possibly through a
free-radical intermediate or as a result of the
action of topoisomerase II. Dactinomycin
inhibits rapidly proliferating cells of normal
and neoplastic origin and is amongst the most
potent antitumor agents known.

Bleomycin
Bleomycin is a small peptide that contains a DNA-binding region and an iron-binding domain
at opposite ends of the molecule. It acts by binding to DNA, which results in single and
double-strand breaks following free radical formation, and inhibition of DNA biosynthesis.
The fragmentation of DNA is due to oxidation of a DNA-bleomycin-Fe(II) complex and leads
to chromosomal aberrations. Bleomycin is a cell cycle– specific drug that causes
accumulation of cells in the G2 phase of the cell cycle.
Bleomycin is indicated for the treatment of Hodgkin’s and non-Hodgkin’s lymphomas, germ
cell tumor, head and neck cancer, and squamous cell cancer of the skin, cervix, and vulva.
PHARMOKINETICS :
One advantage of this agent is that it can be administered subcutaneously, intramuscularly,
or intravenously. Elimination of bleomycin is mainly via renal excretion, and dose
modification is recommended in patients with renal dysfunction. Pulmonary toxicity is dose-
limiting for bleomycin and usually presents as pneumonitis with cough, dyspnea, dry
inspiratory crackles on physical examination, and infiltrates on chest x-ray.The incidence of
pulmonary toxicity is increased in patients older than 70 years of age, in those who receive
cumulative doses greater than 400 units, in those with underlying pulmonary disease, and in
those who have received prior mediastinal or chest irradiation.
In rare cases, pulmonary toxicity can be fatal.

MECHANISM OF ACTION OF BLEOMYCIN
• A DNA-bleomycin-Fe2+ complex
appears to undergo oxidation to
bleomycin Fe3+.
• The liberated electrons react
with oxygen to form superoxide
or hydroxyl radicals, which in
turn attack the phosphodiester
bonds of DNA, resulting in
strand breakage and
chromosomal aberrations.

Plant – derived drugs & their analogs
• VINCA ALKALOIDS- Vincristine, vinblastine and vindesine .
• Derivatives of Podophyllotoxin
• Taxenes :Paclitaxel, Docetaxel.
VINCA ALKALOIDS
• Vincristine,vinblastine and vindesine are main vinca alkaloids used in cancer chemotherapy. These
are obtained from the Madagaskar periwinkle plant formerly known Vinca rosea’
• MECHANISM OF ACTION of Vinblastin
Vinblastin shows its action by binding to tubulin to prevent it from polymerizing into microtubules .
Thus the drug prevents it from polymerizing in microtubules . This leads to inhibition of mitotic spindle
formation by arresting the mitosis at metaphase stage .us the cell division does not occur.
• PHARMACOKINETICS
Vinca alkaloids are usually administered intravenously. Excreted into bile and faeces.
• ADVERSE EFFECTS
• Common unwanted effects include nausea, vomiting,diarrhea, temporary hair loss , painful urination ,
blood in urine or stools ,dizziness .
• CLINICAL USES-. Vincristine is mainly used in treatment of childhood acute leukaemia.
Vinblastine is more potent myelosuppressant and less neurotoxic but causes leucopenia.

Uses of vinblastine
• Vinblastine has been used in
combination therapies for the
treatment of lymphomas ,
testicular cancer and ovarian
cancer . Hodgkin's lymphoma ,
Non-Hodgkin`s lymphoma ,
Kaposi`s sarcoma , mycosis
fungoides .
• Vinblastine is more potent
myelosuppressant and less
neurotoxic but causes leucopenia.
Structure of vinblastine

• Adverse Effects :
loss of sleep, tendon reflexes, severe peripheral neuropathy, some time in
severe condition loss of motor function , foot drop, bone marrow
suppression , constipation ,alopecia(loss of hair from part of the head or
body).
• Therapeutic uses :
vincristine is used combination therapy to treat acute leukaemias,
Hodgkin’s lymphoma , small cell lung cancer , Burkitt’s lymphoma , Brain ,
lung , breast and head and neck cancer .

Taxenes
• Paclitaxel (TAXOL) is derived from the Yew tree and it has the effect of
stabilizing microtubule networks. It has a similar effect as vincristine in that it
prevents interphase microtubule breakdown in G2 so that the mitotic spindle
apparatus cannot form.
These taxanes differ from the vinca alkaloids and colchicine derivatives in that
they bind to a different site on β-tubulin and promote rather than inhibit
microtubule stabilizing tubulin-GDP (Akhmanova and Steinmetz, 2015). The
taxanes have a central role in the therapy of patients with ovarian, breast, lung,
GI, genitourinary, prostate, and head and neck cancers.

• Mechanism of Action
Paclitaxel binds to the β-tubulin subunit on
the inner surface of microtubules and
antagonizes their disassembly with the result
that bundles of microtubules and aberrant
structures derived from microtubules appear
in the mitotic phase of the cell cycle. Arrest in
mitosis follows. Cell death occurs by apoptosis
and depends on both drug concentration and
duration of drug exposure. Drugs that block
cell-cycle progression prior to mitosis
antagonize the toxic effects of taxanes.
• Therapeutic Uses-The taxanes have become
central components of regimens for treating
patients with metastatic ovarian, breast,
lung, GI, genitourinary, and head and neck
cancers. These drugs are administered once
weekly or once every 3 weeks.

• Docetaxel is a semisynthetic taxane derived from the European yew tree. Its mechanism of action, metabolism, and elimination are identical to
those of paclitaxel. It is approved for use as second line therapy in advanced breast cancer and NSCLC, and it also has major activity in head and neck
cancer, small cell lung cancer, gastric cancer, advanced platinum-refractory ovarian cancer, and bladder cancer.
• Docetaxel, somewhat more soluble than paclitaxel, is administered intravenously in an emulsifier
Side effects :
• The following Taxol side effects are common (occurring in greater than 30%) for patients taking Taxol:
• Low blood counts. Your white and red blood cells and platelets may temporarily decrease. This can put you at increased risk for infection, anemia
and/or bleeding.
• Hair loss
• Arthralgias and myalgias, pain in the joints and muscles. Usually temporary occurring 2 to 3 days after Taxol, and resolve within a few days.
• Peripheral neuropathy (numbness and tingling of the hands and feet)
• Nausea and vomiting (usually mild)
• Diarrhea
• Mouth sores
• Hypersensitivity reaction - fever, facial flushing, chills, shortness of breath, or hives after Taxol is given. The majority of these reactions occur within
the first 10 minutes of an infusion. Notify your healthcare provider immediately (premedication regimen has significantly decreased the incidence of
this reaction).
• The following are less common side effects (occurring in 10-29%) for patients receiving Taxol:
• Swelling of the feet or ankles (edema).
• Increases in blood tests measuring liver function. These return to normal once treatment is discontinued (see liver problems).
• Low blood pressure (occurring during the first 3 hours of infusion).
• Darkening of the skin where previous radiation treatment has been given (radiation recall - see skin reactions).
• Nail changes (discoloration of nail beds - rare) (see skin reactions)

Camptothecin Analogues
• The camptothecins are potent, cytotoxic antineoplastic agents
thattarget the nuclear enzyme topoisomerase I. The lead compound
in this class, camptothecin, was isolated from the tree Camptotheca
acuminata. Irinotecan and topotecan, currently the only
camptothecin analogues approved for clinical use, have activity in
colorectal, ovarian, and small cell lung cancer.

MECHANISM OF ACTION OF IRINOTECAN
&TOPOTECAN
Normal unwinding of double helix Irinotecan and
topotecan are inhibit the unwinding of double
helix
Irinotecan and Topotecan are semisynthetic derivatives.These
drugs are S-phase specific. They inhibit topoisomerase I, which is
essential for the replication of DNA in human cells.

Side effects :
• Diarrhea (4-6 episodes in a 24-hour period) despite use of anti-diarrhea medication and diet modifications.
• Nausea (interferes with ability to eat and unrelieved with prescribed medication).
• Vomiting (vomiting more than 4-5 times in a 24 hour period)
• Extreme fatigue (unable to carry on self-care activities)
• Mouth sores (painful redness, swelling or ulcers)
• Insomnia (see sleep problems)
• Cough
• Headache
• Dehydration
• Chills (see flu-like symptoms)
• Skin rash (see skin reaction)
• Flatulence (the accumulation of gas in the alimentary canal)
• Flushing of face during infusion
• Mouth sores
• Heartburn
• Swelling of feet and ankles

Epipodophyllotoxins
• Podophyllotoxin extracted from the mandrake plant (may apple
:Podophyllum peltatum ) Two synthetic derivatives of
podophyllotoxins have significant therapeutic activity in pediatric
leukemia, small cell carcinomas of the lung, testicular tumors,
Hodgkin disease, and large cell lymphomas. These derivatives are
etoposide (VP-16-213) and teniposide (VM-26). Although
podophyllotoxin binds to tubulin, etoposide and teniposide have no
effect on microtubular structure or function at usual concentrations
• etoposide given in tablet form by mouth.
• As an infusion into the vein (intravenous, IV), as a short infusion or as
a continuous infusion over 24 hours.

Normal catalytic cycle of topoisomerase
which is inhibited by the Etoposide and its
analog, teniposide
Etoposide and its analog, teniposide are semisynthetic derivatives of the
plant alkaloid, They block cells in the late S to G2 phase of the cell cycle.
Their major target is topoisomerase II. Binding of the drugs to the enzyme-
DNA complex results in persistence of the transient, cleavable form of the
complex and, thus, renders it susceptible to irreversible double-strand
breaks

Side effects :
• Hair loss
• Menopause (chemotherapy induced)
• Loss of fertility. Meaning, your ability to conceive a child may be affected by etoposide.
Discuss this issue with your health care provider.
• Nausea and vomiting (especially at high-doses)
• Low blood pressure (if the drug is infused too fast)
• Mouth sores (especially at high doses)
• Diarrhea (especially at high doses)
• Poor appetite
Other side effects:
• Metallic taste during infusion of drug
• Inflammation at injection site
• Peripheral neuropathy (numbness in your fingers and toes) may occur with repeated doses.
This is a rare side effect but can be irreversible. Report numbness or tingling of feet or hands
to your health care provide

Targeted cancer therapies?
• Targeted cancer therapies are drugs or other substances that block the growth
and spread of cancer by interfering with specific molecules ("molecular
targets") that are involved in the growth, progression, and spread of cancer.
Targeted cancer therapies are sometimes called "molecularly targeted drugs,"
"molecularly targeted therapies," "precision medicines," or similar names.
• Targeted therapies differ from standard chemotherapy in several ways:
• Targeted therapies act on specific molecular targets that are associated with
cancer, whereas most standard chemotherapies act on all rapidly dividing
normal and cancerous cells.
• Targeted therapies are deliberately chosen or designed to interact with their
target, whereas many standard chemotherapies were identified because they
kill cells.
• Targeted therapies are often cytostatic (that is, they block tumor cell
proliferation), whereas standard chemotherapy agents are cytotoxic (that is,
they kill tumor cells).

Types of targeted cancer therapies available -
• Hormone therapies slow or stop the growth of hormone-sensitive tumors, which require certain hormones to grow. Hormone therapies
act by preventing the body from producing the hormones or by interfering with the action of the hormones. Hormone therapies have been
approved for both breast cancer and prostate cancer.eg – Tomoxifen .
• Signal transduction inhibitors block the activities of molecules that participate in signal transduction, the process by which a cell responds
to signals from its environment. During this process, once a cell has received a specific signal, the signal is relayed within the cell through a
series of biochemical reactions that ultimately produce the appropriate response(s). In some cancers, the malignant cells are stimulated to
divide continuously without being prompted to do so by external growth factors. Signal transduction inhibitors interfere with this
inappropriate signaling.
• Gene expression modulators modify the function of proteins that play a role in controlling gene expression.
• Apoptosis inducers cause cancer cells to undergo a process of controlled cell death called apoptosis. Apoptosis is one method the body
uses to get rid of unneeded or abnormal cells, but cancer cells have strategies to avoid apoptosis. Apoptosis inducers can get around these
strategies to cause the death of cancer cells.
• Angiogenesis inhibitors block the growth of new blood vessels to tumors (a process called tumor angiogenesis). A blood supply is
necessary for tumors to grow beyond a certain size because blood provides the oxygen and nutrients that tumors need for continued
growth. Treatments that interfere with angiogenesis may block tumor growth. Some targeted therapies that inhibit angiogenesis interfere
with the action of vascular endothelial growth factor (VEGF), a substance that stimulates new blood vessel formation. Other angiogenesis
inhibitors target other molecules that stimulate new blood vessel growth.
• Immunotherapies trigger the immune system to destroy cancer cells. Some immunotherapies are monoclonal antibodies that recognize
specific molecules on the surface of cancer cells. Binding of the monoclonal antibody to the target molecule results in the immune
destruction of cells that express that target molecule. Other monoclonal antibodies bind to certain immune cells to help these cells better
kill cancer cells.
• Monoclonal antibodies that deliver toxic molecules can cause the death of cancer cells specifically. Once the antibody has bound to its
target cell, the toxic molecule that is linked to the antibody—such as a radioactive substance or a poisonous chemical—is taken up by the
cell, ultimately killing that cell. The toxin will not affect cells that lack the target for the antibody—i.e., the vast majority of cells in the body.

Miscellaneous anti-cancer drugs: Clinical activity and toxicities.

Imatinib(GLEEVAC)
• Mechanism of Action
Imatinib binds to Bcr/Abl protein
very close to the binding site of
ATP, blocking ATP from binding.
Without the binding of ATP, Bcr/Abl
cannot phosphorylate substrate
proteins. Imatinib is very specific to
this sub-family of receptor tyrosine
kinases.
Blocking the ability of Bcr/Abl stops
several transduction pathways that
cause the excessive proliferation of
partially differentiated cells that
lead to CML. The main oncogenes
that are inhibited are Ras, Myc, and
STAT. Each of these oncogenes
cause a signal cascade that cause
cell proliferation.

Herceptin
• Herceptin (chemical name: trastuzumab) can be used to treat HER2-positive breast
cancer that is either early-stage or advanced-stage/metastatic.
• Herceptin is currently approved by the U.S. Food and Drug Administration:
• to treat metastatic HER2-positive breast cancer to stop the cancer from growing
• to treat earlier stages of HER2-positive breast cancer, either as part of a regimen with
chemotherapy or alone after a chemotherapy regimen that includes an anthracycline,
to reduce the risk of the breast cancer coming back (recurrence)
• in combination with Perjeta (chemical name: pertuzumab) and Taxotere (chemical
name: docetaxel) before surgery to treat HER2-positive, early-stage (the cancer must
be larger than 2 cm or cancer must be in the lymph nodes), inflammatory, or locally
advanced-stage breast cancer with a high risk of metastasizing or becoming fatal
• in combination with Perjeta and chemotherapy after surgery to treat HER2-positive,
early-stage breast cancer with a high risk of recurrence

Herceptin side effects
• Most common side effects of Herceptin are headache , diarrhea ,
nausea , chills , fever , , infection , insomnia , cough , rashes, heart
problems serious heart problems, including some that don’t have
symptoms, such as reduced heart function, and some that do have
symptoms, such as congestive heart failure. Symptoms to watch for
include swelling of the ankles or legs, shortness of breath, cough, or
weight gain of more than 5 pounds in less than 24 hours. etc .
• Lung problems -Herceptin may cause inflammation of the lungs,
which can be life-threatening. Symptoms include trouble breathing,
cough, tiredness, and fluid in the lungs

Mechanism of Action Of
Trastuzumab(Herceptin)

Rituxan(Rituximab )
• Rituximab is an intravenous drug that is used to treat rheumatoid
arthritis and B-cell non-Hodgkin's lymphoma
• Tumor cells (like most normal cells) have receptors on their surfaces.
Many kinds of chemicals, proteins, etc., on the outside of the cell can
attach to these receptors. When they do, they can cause changes to occur
within the cells. One receptor, present in more than 90% of B-cell non-
Hodgkin's lymphomas, is called CD20. Molecules that attach to CD20 can
affect the growth and development of the tumor cells and, sometimes, the
production of new tumor cells
• Rituximab was approved by the FDA in 1997

Uses Of Rituximab :
Rituximab is used for the treatment of:
• Non-Hodgkin's B-cell lymphomas that have CD20 receptors on their
surface. It is used when lymphomas recur following other types of therapy
or are unresponsive to other types of therapy.
• Chronic lymphocytic leukemia
• Granulomatosis with polyangiitis
• Microscopic polyangiitis
• Rituximab also is combined with methotrexate (Rheumatrex, Trexall) to
treat rheumatoid arthritis in patients who have failed other biologic
medications, such as infliximab (Remicade), etanercept (Enbrel), or
adalimumab (Humira)

Side effects of Rituximab -
• most common side effect of rituximab is a constellation of symptoms (fever, rigors and chills) that occur during
administration of the first dose of drug.
• Nausea
• Hives
• Fatigue
• Headache
• Itching
• Difficulty breathing due to bronchospasm
• A sensation of swelling of the tongue or throat
• Runny nose
• Vomiting
• Decreased blood pressure
• Flushing
• Pain at the site of the tumor
• Irregular heart rhythms and infection are two other rarely-occurring side effects that may be severe.

Avastin( Bevacizumab)
• A recombinant humanized monoclonal antibody directed against the vascular
endothelial growth factor (VEGF), a pro-angiogenic cytokine. Bevacizumab binds
to VEGF and inhibits VEGF receptor binding, thereby preventing the growth and
maintenance of tumor blood vessels.
Use in Cancer
• Bevacizumab is approved to be used alone or with other drugs to treat:
Cervical cancer, Colorectal cancer, Glioblastoma ,
Nonsquamous non-small cell lung cancer that is locally advanced,
cannot be removed by surgery, has metastasized, or has recurred,
• Ovarian epithelial, fallopian tube, or primary peritoneal cancer. It is
used in patients with stage III, stage IV.
• Renal cell carcinoma (a type of kidney cancer) that has metastasized. It
is used with interferon alpha.

Mechanism of action of Avastin ( Bevacizumab)

side effects
• Generalized weakness
• Pain
• Abdominal pain
• Nausea and vomiting
• Poor appetite
• Constipation
• Upper respiratory infection
• Low white blood cell count.
(This can put you at
increased risk for infection.)
• Proteinuria
• Nose bleed
• Diarrhea
• Hair loss
• Mouth sores
• Headache
• Gastrointestinal
perforation/ fistula
formation/ wound
healing complications
• Hemorrhage (severe
bleeding)
• Hypertensive crisis
(severe high blood
pressure)

BCL2 Inhibitors
The BCL2 protein family comprises more than 20 proteins that govern
mitochondrial outer membrane permeabilization and control programmed cell
death (apoptosis). Proteins in this family can be either pro or anti-apoptotic
depending on their content of BCL2 homology domains (BH1 to 4).
Pro-apoptotic proteins contain a BH3 domain that is necessary for dimerization
with other proteins of the BCL2 family.
Anti-apoptotic proteins contain BH1 and BH2.
The balance of these interacting proteins controls mitochondrial outer
membrane permeabilization, cytochrome c release, and the activation of
caspases that leads to apoptosis .BCL2 promotes cellular survival by inhibiting
pro-apoptotic proteins like BIM, BAX, and BAK and is overexpressed in CLL and
some other tumors where it can support tumor cell survival and resistance to
cancer treatments

Mechanism of action of Venetoclax
• Venetoclax is a small molecule type of
targeted therapy. Venetoclax is a pill that
promotes apoptosis, a common way by
which cells die. It does this by binding to
BCL-2, an anti-apoptotic protein.
Overexpression of BCL-2 has been
demonstrated in CLL cells where it
mediates tumor cell survival and has
been associated with resistance to
chemotherapies. Venetoclax helps
restore the process of apoptosis by
binding directly to the BCL-2 protein,
displacing pro-apoptotic proteins.
Venetoclax blocks an important pathway
that promotes cell survival in tumor cells
that overexpress BCL-2, so venetoclax
causes cells to die (pro-apoptotic).

The following side effects are common
(occurring in greater than 30%) for
patients taking venetoclax:
-Low white blood cell counts (increases
risk of infection)
-Diarrhea
Nausea
These side effects are less common side
effects (occurring in about 10-29%) of
patients receiving venetoclax:
-Anemia
-Low platelets (increases risk of bleeding)
-Upper respiratory tract infection (cold
symptoms)
-Fatigue
-High potassium in the blood
-Fever
-Vomiting
-Headache
-High phosphate in the blood
-Constipation
-Cough
-Low potassium in the blood
-Swelling
-Back pain
Tumor Lysis Syndrome- may occur as a
result of leukemia treatment. Tumor lysis
syndrome occurs when large amounts of
cancerous cells are rapidly killed by the
therapy. These cells release uric acid,
potassium, and phosphorous into the
blood stream. Tumor lysis syndrome can
lead to kidney failure. Tumor lysis
syndrome usually occurs within 24-48
hours of therapy.
Side Effects:

Tamoxifen
• Tamoxifen or tamoxifen citrate is a non steroidal Selective
Estrogen Receptor Modulator (SERM).
• Estrogen receptor exist in different tissues like Brain ,
breast , lung , liver , bone , uterus .
• The normal cellular function of the estrogen receptors are
transcription factor synthesis and the cell proliferation.
• Tamoxifen increases disease-free survival and overall
survival; treatment for 5 years reduces cancer recurrence
by 50% and death by 27% and is more efficacious than
shorter 1- to 2-year treatment periods .

How tamoxifen works?
• hormone receptor-positive breast cancers
need estrogen and/or progesterone
(female hormones produced in the body)
to grow.
• Tamoxifen attaches to the hormone
receptor in the cancer cell, blocking
estrogen from attaching to the receptor.
This slows or stops the growth of the
tumor by preventing the cancer cells from
getting the hormones they need to grow.
• Antagonist in breast and brain cause no
transcription , and no cell growth arrest/
apoptosis .
• While tamoxifen is agonist in lung, liver,
bone and uterus .

Side effects :
• Hot flushes
• nausea
• vomiting

CAR T-cell therapy
l
Chimeric antigen receptor (CAR) T immunotherapy is one of the most promising
modern approaches for the treatment of cancer. To date only two CAR T-cell products,
Kymriah® and Yescarta®, have been approved by the Food and Drug Administration
(FDA) for the treatment of lymphoblastic leukemia and B-cell lymphoma.
Administration of CAR T-cells to control solid tumors has long been envisaged as one
of the most difficult therapeutic tasks. A type of treatment in which a patient's T cells (a
type of immune system cell) are changed in the laboratory so they will attack cancer
cells. T cells are taken from a patient’s blood. Then the gene for a special receptor that
binds to a certain protein on the patient’s cancer cells is added in the laboratory. The
special receptor is called a chimeric antigen receptor (CAR). Large numbers of the
CAR T cells are grown in the laboratory and given to the patient by infusion. CAR T-
cell therapy is being studied in the treatment of some types of cancer. Also called
chimeric antigen receptor T-cell therapy.

a patient’s T cells (a type of
immune cell) are changed in the
laboratory so they will bind to
cancer cells and kill them.
Blood from a vein in the
patient’s arm flows through a
tube to an apheresis machine
which removes the white blood
cells, including the T cells, and
sends the rest of the blood back
to the patient.
Then, the gene for a special
receptor called a chimeric
antigen receptor (CAR) is
inserted into the T cells in the
laboratory.
Millions of the CAR T cells are
grown in the laboratory and
then given to the patient by
infusion. The CAR T cells are able
to bind to an antigen on the
cancer cells and kill them.

Side Effects of CAR T-Cell Therapy
• Cancer treatments like chemotherapy and radiation kill both cancer cells and
healthy cells, which is why they can cause things like nausea, vomiting, and
infections. Because CAR T-cell therapy targets only cancer cells, it doesn’t
lead to those. But it can cause a few other health issues

S.No Common name Condition or Diseases treated Generic name
1 Revlimid Multiple myeloma Lenalidomide
2 Keytruda Advanced melanoma; non-small cell lung cancer; head and
neck squamous cell cancer
Pembrolizumab
3 Herceptin HER2+ breast cancer Trastuzumab
4 Avastin Breast, colorectal, lung, kidney, ovarian cancers Bevacizumab
5 Rituxan Non-Hodgkins Lymphoma, chronic lymphocytic leukemia Rituximab
6 Imbruvica Mantel cell lymphoma, chronic lymphocetic leukemia Ibrutinib capsules
7 Gardasil Cervical cancer Human Papillomavirus Quadrivalent
(Types 6,11, 16, and 18) Vaccine,
Recombinant
8 Perjeta HER2-positive breast cancer Pertuzumab
9 Alimta Non-small cell lung cancer Pemetrexed
10 Tasigna Chronic myeloid leukemia Nilotinib
11 Opdivo Non-small cell lung cancer; metastatic melanoma; renal cell
carcinoma; classical Hodgkin lymphoma
Nivolumab
12 Xgeva Bone metastases Denosumab
13 Zytiga Prostate cancer Abiraterone acetate
14 Revolade long-term immune thrombocytopenic purpura Promacta
15 Gleevec Chronic myeloid leukemia, gastrointestinal stromal tumors Imatinib
16 Afinitor Breast cancer Everolimus
Top 20 DRUGS USED IN YEAR 2018 for treatment of cancer

Q 1-At which phase of cell cycle does cis-platin work?
(A) S phase
(B) G1 phase
(C) Cisplatin is not cell cycle specific , although it induces cell cycle arrest .
(D) G2 phase
Q2- A client with a sarcoma isvreceiving Bleomycin . The nurse in charge with the client expect
the physician to order which diagnostic procedure ?
(A) Pulmonary function studies (PFT’s)
(B) Stress test
(C) Cranial x-ray
(D) Electrocardiogram (ECG)
Q3-The client is receiving Cisplatin (Platinol-AQ). Which of the following side effect is related to
the medication?
(A) Depressed tendon reflexes
(B) Photosensitivity
(C) Tinnitus
(D) Ptosis

4 ) Which statements apply to the estrogen receptor?
A. It is a good predictive marker for response to endocrine treatment
in patients with breast cancer
B. The expression of the estrogen receptor is confined to breast tissue
C. It is located on the outer cell surface of breast cells
D. Estrogen receptor status is associated with specific sites of
metastatic spread in breast cancer patients

CASE STUDIES1 -During a routine follow-up visit, WM, a 48-year-old female, complains of ongoing
fatigue since the beginning of cytotoxic chemotherapy, 6 months after initiating
trastuzumab.
Physical Exam
• At 6 months following initiation of single-agent trastuzumab, a multigated acquisition
(MUGA) scan revealed left ventricular ejection fraction (LVEF) dropped to 49% (baseline
67%; post doxorubicin/cyclophosphamide 65%)
• Otherwise asymptomatic • Absence of shortness of breath• No jugular venous
distention, pulmonary rales, or lower extremity edema
Relevant Medical History
• Diagnosed with HER2/neu-positive breast cancer with two of 14 positive lymph nodes
• Patient underwent postsurgical radiation to the chest wall and a treatment plan
consisting of four cycles of doxorubicin/cyclophosphamide, followed by 12 weeks of
paclitaxel plus trastuzumab for 1 year
• The patient continues to undergo cardiac evaluation every 3 months while on
trastuzumab

Which of the following would be the best course of action for this patient?
(a) Permanently discontinue trastuzumab and refer her to cardiology
(b) Temporarily hold trastuzumab and obtain another MUGA in 1 month; if
LVEF returns to baseline continue trastuzumab therapy, and reassess in 1
month
(c) Temporarily hold trastuzumab and obtain another MUGA in 1 month, if
abnormal start lapatinib
(d) Continue trastuzuamb therapy and obtain another MUGA in 1 month
Correct answer (b)
Explanation :The cardiotoxicity resulting from trastuzumab use may be reversible
and LVEF may return to baseline for many patients after temporary discontinuation
of trastuzumab. If WM does recover her cardiac function, resumption of
trastuzumab therapy can be considered. Given WM’s high risk for breast cancer
relapse, a retrial of trastuzumab after full LVEF recovery would be reasonable.

CASE STUDY
2 ) A 23-year-old patient with Hodgkin lymphoma was seen as an in patient
consultation for a pruritic rash that had been present for two days. The man
was being treated with the ABVD chemotherapy regimen (doxorubicin,
bleomycin, vinblastine, dacarbazine [DTIC-Dome]). Family history was
noncontributory.A review of systems was negative for fevers but positive
for chills and weight loss in the setting of chemotherapy. Social history was
negative for recent consumption of shiitake mushrooms. Physical exam was
notable for linear hyperpigmented streaks on the trunk and extremity.

What's your diagnosis?
(a) Dermatomyositis
(b) Phytophotodermatitis
(c) Flagellate hyperpigmentation
(d) Poison ivy
correct answer –(c) Flagellate hyperpigmentation
• Explanation-
• When used in the treatment of malignancies, bleomycin causes adverse cutaneous and
pulmonary reactions in 50% and 10% of treated patients, respectively.1 The cutaneous
side effects of bleomycin include those common to all chemotherapeutic agents, including
alopecia and stomatitis.1
• Hyperpigmentation is a common cutaneous side effect of systemic bleomycin. Flagellate
hyperpigmentation — seen in this patient — is a pathognomonic cutaneous side effect of
bleomycin and manifests as hyperpigmented linear streaks, found most commonly on the
chest and back. Flagellate pigmentation from bleomycin, also known as flagellate
erythema, scratch dermatitis, and flagellate dermatitis, may occur in as many as 10% to
20% of patients treated with systemic bleomycin.2

CASE STUDY 3
• Upon laboratory testing, SL, a 64-year-old female diagnosed with Philadephia chromosome–
positive (Ph+) ALL, was found to be anemic (Hgb=7 g/dL) and neutropenic (ANC=600
cells/mcL) after her second course of maintenance therapy.
• Relevant Medical History
• Currently, SL is taking vincristine, prednisone, methotrexate, and mercaptopurine (POMP) +
dasatinib maintenance therapy for her Ph+ ALL
• Recently complained of occasional heartburn
• Laboratory History
• • Laboratory results were normal after the first course of therapy
• On day 29 of the second course, chemotherapy for SL was held secondary to anemia and
neutropenia
• Medication History
• • Vincristine 2 mg intravenous piggy back on Day 1 repeated every 28 days
• Prednisone 20 mg/m2/dose orally twice daily on Days 1-5 repeated every 28 days
• Methotrexate 20 mg/m2 orally once weekly
• Mercaptopurine 75 mg/m2 orally daily
• Omeprazole 20 mg orally daily (over-the-counter)
• Morphine 15 mg immediate release every 4 hours as needed for pain
• Docusate 100 mg orally twice daily
• Dasatinib 140 mg orally daily

• Based on review of medications, you discover there is a drug-drug interaction causing the changes in SL’s
laboratory results. Which of the following drug/drug interactions is responsible for the myelosuppression in SL?
(A)Omeprazole and Dsatinib
(B)Methotrexate and omeprazole
(C)Mercaptopurine and omeprazole
(D)No drug interaction exist
Correct answer: (B)Methotrexate and omeprazole
Explanation :
• First, is there is evidence that H+/K+– ATPase is present in renal epithelium as well as gastric parietal cells. It is
suggested that PPIs, specifically, inhibit the renal H+/K+– ATPase, which supports the active tubular secretion of
methotrexate and subsequently increase the half-life of methotrexate.
• A second proposed mechanism involves possible PPI inhibition of ATP-dependent efflux of methotrexate by
breast cancer resistant protein (BCRP) in human kidney proximal tubules. Several case reports have been
published regarding the interaction between methotrexate and PPIs. Most of the case reports are with high-
dose methotrexate.

CASE STUDY
56-year-old Caucasian woman presented to her primary care physician with a 3-month history of
intermittent bright red rectal blood with defecation. At her initial visit, a digital rectal examination,
anoscopy, and a pelvic examination with DNA testing for high-risk human papillomavirus (HPV) were
performed; all results were negative. She was referred for a colonoscopy, which revealed an abnormal area
with a 3 × 4–cm mass in the rectum at a distance of 10 cm from the anal verge. Colonoscopic biopsy of this
mass was consistent with invasive squamous cell carcinoma (Figures 1A and 1B); p16 immunohistochemistry
staining of the biopsy specimen was positive (Figure 1C). Staging workup with a total body CT scan (Figure
2A) and positron emission tomography (PET)/CT scan (Figure 2B) confirmed the presence of a rectal mass,
which demonstrated a standardized uptake value of 10. There was no evidence of nodal or distant
metastasis. The patient was referred to medical oncology for further treatment recommendations.
Q - For which of the following treatment plans does the available evidence provide the strongest support?
A. Neoadjuvant therapy with continuously infused fluorouracil (5-FU) and concurrent radiation
therapy,followed by total mesorectal excision
B. Low anterior resection or abdominoperineal resection followed by adjuvant chemoradiation therapy
C. Radiation therapy only
D. Definitive chemoradiation therapy with continuously infused 5-FU on days 1–4 and days 29–32 and
mitomycin on days 1 and 29, along with concurrent radiation therapy

ANSWER
• The anatomic and histologic similarities between squamous cell
rectal and anal cancers have led to an emerging trend of utilizing
chemoradiation either as definitive treatment or in conjunction with
salvage surgery, if needed, in the management of squamous cell
rectal carcinoma. Because of improvements in chemotherapy and
radiotherapy, as well as in the imaging technology used to
determine stage and response in this disease, a number of recent
studies utilizing an anal squamous cell carcinoma–based treatment
approach have shown promising results in patients with rectal
squamous cell carcinoma.
• However, in the setting of a partial response to definitive
chemoradiation or stable disease, a more prolonged assessment of
up to 6 months from completion of treatment can be appropriate
before considering salvage surgery. Many patients who eventually
have a pathologic complete response have been known to have
clinical and radiologic findings suggestive of persistent disease in
the early post-chemoradiation phase. This also is in line with the
accepted management of anal squamous cell cancers, in which a
delayed tumor response may occur as long as 6 months after the
completion of chemoradiation.
• SO, ANSWER D may seems to be correct .

Ques1- what will be your diagnostic test/procedures for this patients ?
and why?
Ques 2- What other tests do you plan to request? include additional
immunohistological &laboratory requests for staging system?

• Ans 1- mammogram , biopsy
• Diagnostic mammography aimed at evaluating the rest of breast before biopsy
is performed or occasionally is part of triple test strategy to exclude immediate
biopsy. They include densities micro calcifications , lesions etc.
• Ans 2-IHC is a special staining process performed on fresh or frozen breast
cancer tissue during biopsy, done to check whether or noty the cancer have
HER2 receptors &/or hormone receptors on their surfaces
Biomarker test include TRU-QUANT , CA27.29, CA125, CEA 9 carcinoembryonic
antigen ). Include familial clustering & inherited germline abnormalities .

• MCQ’s Answers
Q2 – (A) Bleomycin (Blenoxane) is an antitumor antibiotic that can cause interstitial
pulmonary fibrosis. Pulmonary function tests and chest x-ray are done while on this
treatment.
Q3- -(c) Cisplatin (Platinol-AQ), an alkylating medication, may cause ototoxicity,
tinnitus(perception of noise or ringing in the ears)., hypokalemia, hypomagnesemia,
hypocalcemia and nephrotoxicity. Option A: is a sign of hypermagnesemia.
• Q4 ) A&D TRUE statements B&C FALSE stateents
• Explanation:
A: The estrogen receptor status strongly predicts the response to hormonal treatment in
patients with breast cancer, both in the adjuvant ( absolute risk reduction of 10-15% with
regard to breast cancer mortality) and metastatic setting (approximately 50-60%
response in first line treatment).
B: Estrogen expression is not confined to breast tissue. E.g.: Also endometrial cells,
ovarian cancer cells can express the receptor.
C: The estrogen receptor belongs to the nuclear hormone receptor family, is located at
the nuclear membrane in the cytosol of the cell ( not on the outer membrane)
D: ER positive breast cancers are more likely to cause apparent metastatic disease in
bones, genital tract and soft tissue than ER negative tumours.

References
• https://www.cancernetwork.com/
• https://www.cancer.gov/
• http://chemocare.com/
• Goodman & Gilman's: The Pharmacological Basis of Therapeutics,
13e
• Basic and Clinical Pharmacology 14th Edition
• The Organic Chemistry of Drug Design and Drug Action 3rd Edition
• https://www.oncologyanalytics.com/
• https://www.drugbank.ca/

Drugs used in cancer.pptm

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