Antineoplastic agents

• Alkylating agents: cyclophosphamide,

chlorambucil, busulphan, uracil, mustard.
• Antimetabolites: mercaptopurine, flurouracil,
methotrexate, azothioprine.
• Antibiotics: Doxorubicin, Mitomycin.
• Plant products : Etoposide,
Vincristine,Vinblastine, Taxol.
• Miscellaneous : Cisplatin.
• Hormones : Mitotane, Tamoxifen.
• Immunotherapy : Interferon alpha 2a and 2b.
Molecular
Biology of
Cancer
A thorough knowledge of the
kinetics of tumor cell proliferation
along with an understanding of the
pharmacology and mechanism of
action of cancer chemotherapeutic
agents is important in designing
optimal regimens for patients with
cancer.
The strategy for developing drug regimens
requires knowledge of the particular
characteristics of specific tumors. For example,
is there a high growth fraction?
Is there a high spontaneous cell death rate?
Are most of the cells in G0?
Is a significant fraction of the tumor composed of
hypoxic stem cells?
Are their normal counterparts under hormonal
control?
Similarly, knowledge of the pharmacology of
specific drugs is important.
Are the tumor cells sensitive to the drug?
Is the drug cell cycle-specific?
Does the drug require activation in certain normal
tissue such as the liver (cyclophosphamide), or is
it activated in the tumor tissue itself
(capecitabine)?
Similarly, for some tumor types, knowledge of
receptor expression is important. For example,
in patients with breast cancer, analysis of the
tumor for expression of estrogen is important in
guiding therapy.
In general, it is preferable to use cytotoxic
chemotherapeutic agents in intensive pulse
courses every 3-4 weeks rather than to use
continuous daily dosage schedules.
This schedule allows for maximum effects against
neoplastic cell populations with complete
hematologic and immunologic recovery between
courses rather than leaving the patient
continuously suppressed with cytotoxic therapy.
This approach reduces adverse effects but does
not reduce therapeutic efficacy.
Schematic of the cell cycle. outer ring: I = Interphase, M =
Mitosis; inner ring: M = Mitosis, G1 = Gap 1, G2 = Gap 2,
S = Synthesis; not in ring: G0 = Gap 0/Resting
Each turn of the cell cycle divides the
chromosomes in a cell nucleus.
Antineoplastic agents
DNA Double Helix
DNA replication. The
double helix is
unwound and
each strand acts as
a template for the
next strand. Bases
are matched to
synthesize the
new partner
strands
Action of DNA Polymerase
Antineoplastic agents
DNA Replication
Antineoplastic agents
DNA
Stages of cancer developments
Cancers are caused by a series of mutations. Each
mutation alters the behavior of the cell somewhat.
Stages of cancer developments

Cancer Introduction
Stages of Cancer Development
CLASSIFICATION OF ANTICANCER DRUGS
1. Polyfunctional alkylating agents
o Nitrosoureas
o Mustards (Nitrogen Mustards)
o Methanesulphonates (Busulphan)
o Ethylenimines
2. Other Alkylating Drugs
o Procarbazine
o Dacarbazine
o Cisplatin
3. Antimetabolites
o Antifolate(Methotrexate)
o Amino acid Antagonists (Azaserine)
4. Purine antagonists
o Mercaptopurine (6-MP)
o Thioguanine (6-TG)
CLASSIFICATION OF ANTICANCER DRUGS ………….
5. Pyrimidine antagonists
o Fluorouracil (5-FU)
o Cytarabine
6. Plant alkaloids
o Vinblastine
o Vincristine
o Etoposide
o Teniposide
o Topotecan
o Taxol (Paclitaxel)
o Docetaxel (Taxotere)
7. Antibiotics
o Anthracyclines
o Doxorubicin (Adriamycin)
o Daunorubicin
o Dactinomycin
o Idarubincin
o Mitomycin
o Bleomycin
CLASSIFICATION OF ANTICANCER DRUGS
8. Monoclonal Antibodies
o Examples
9. Hormonal agents
o Tamoxifen
o Flutamide
o Gonadotropin-Releasing Hormone Agonists
o (Leuprolide and Goserelin
o Aromatase Inhibitors
o Aminoglutethimide
o Anastrozole
10. Miscellaneous anticancer drugs
o Hydroxyurea
o Asparaginase
o Mitotane
o Retinoic Acid Derivatives
•
o Bone Marrow Growth Factors
Chemical Classification of alkylating agents
1. Alkyl sulfonates : Busulfan
2. Ethyleneimines and methylmelamines -
Hexamethylmelamine and Thiotepa.
3. Nitrogen mustards -Cyclophosphamide,
Chlorambucil, Ifosfamide, uramustine and
Melphalan
4. Nitrosoureas - mustine, lomustine and
Carmustine.
5. Triazenes - Dacarbazine
6. Imidazotetrazines – Temozolomide.
7. Alkylating Like - Platinum compound - Cisplatin
Mode of Action of
Antitumor Drugs
The cytotoxic and other effects of the alkylating
agents are directly related to the alkylation of
components of DNA.
The 7 nitrogen atom of guanine is particularly
susceptible to the formation of a covalent bond
with both monofunctional and bifunctional
alkylators and may well represent the key target
that determines the biological effects of these
agents.
It must be appreciated, however, that other atoms in
the purine and pyrimidine bases of DNA-for
example, the 1 or 3 nitrogens of adenine, the 3
nitrogen of cytosine, and the 6 oxygen of guanine-
may also be alkylated to a lesser degree, as are the
phosphate atom of the DNA chains and the proteins
associated with DNA.
Alkylating agents:
Cyclophosphamide,
Chlorambucil,
Busulphan, uracil mustard.
Chemical Classification of Alkylating Agents
1. Nitrogen mustards: Mechlorethamine,
Cyclophosphamide, Ifosfamide
2. Ethylenimines and Methylmelamines:
Altretamine, Thiotepa,
3.Alkyl Sulfonates: Busulfan,
4. Nitrosoureas: Carmustine
5. Triazenes: Dacarbazine
6. Methylhydrazines: Procarbazine
7. PLATINUM COORDINATION COMPLEXES:
Cisplatin and Carboplatin
Many of the agents are known as "Classical alkylating
agents". These include true alkyl groups, and have
been known for a longer time than some of the
other alkylating agents. Examples include
melphalan and chlorambucil.
The following three groups are almost always
considered "classical".
Nitrogen mustards
– Cyclophosphamide
– Mechlorethamine or mustine
– Uramustine or uracil mustard
– Melphalan
– Chlorambucil
– Ifosfamide
Nitrosoureas
– Carmustine
– Lomustine
– Streptozocin
Alkyl sulfonates
– Busulfan
Thiotepa and its analogues are usually
considered classical, but can be considered
nonclassical.
The chemotherapeutic alylating agents have in
common the property of undergoing strongly
electrophilic chemical reactions through the
formation of carbonium ion intermediates or of
transition complexes with the target molecules.
These reactions result in the formation of covalent
linkages (alkylation) with various nucleophilic
substances, including such biologically important
moieties as phosphate, amino, sulfydryl,
hydroxyl, carbonyl, and imidozole groups.
Nitrogen Mustards
Alkylating Mechanism of Mechlorethamine With
Guanine Base:
SAR of Alkylating Agents
SAR
1. The alkylating agents used in chemotherapy share the
capacity to contribute alkyl groups to biologically vital
macromolecules such as DNA.
2. Modification of the basic chloroethylamine structure
changes reactivity, lipophilicity, active transport across
biological membranes, sites of macromolecular attack, and
mechanisms of DNA repair, all of which properties
determine drug activity in vivo.
3. With several of the most valuable agents (e.g.,
cyclophosphamide and ifosfamide), the active alkylating
moieties are generated in vivo after metabolism.
SAR……
4. The biological activity of nitrogen mustards is based
upon the presence of the bis-(2-chloroethyl) grouping.
While mechlorethamine has been widely used in the
past, linkage of the bis-(2-chloroethyl) group to
election-rich substitutions such as unsaturated ring
systems has yielded more stable drugs with greater
selective killing of tumor cells.
5. Bis-(2-chloroethyl) groups have been linked to amino
acids (phenylalanine) and substituted phenyl groups
(aminophenol butyric acid, as in chlorambucil) in an
effort to make a more stable and orally available form.
SAR
6. A classical example of the role of host metabolism in
the activation of an alkylating agent is seen with
cyclophosphamide, now the most widely used agent of
this class.
7. Ifosfamide is an oxazaphosphorine, similar to
cyclophosphamide. Cyclophosphamide has two
chloroethyl groups on the exocyclic nitrogen atom,
whereas one of the two-chloroethyl groups of
ifosfamide is on the cyclic phosphoamide nitrogen of
the oxazaphosphorine ring.
8. Ifosfamide is activated in the liver by CYP3A4.
The activation of ifosfamide proceeds more
slowly, with greater production of dechlorinated
metabolites and chloroacetaldehyde.
These differences in metabolism likely account for
the higher doses of ifosfamide required for
equitoxic effects, the greater neurotoxicity of
ifosfamide, and the possible differences in
antitumor spectrum of the two agents.
Cyclosphosphamide
Efforts to modify the chemical structure of
mechlorethamine to achieve greater
selectivity for neoplastic tissues led to the
development of cyclophosphamide.
After studies of the pharmacological activity
of cyclophosphamide, clinical
investigations by European workers
demonstrated its effectiveness in selected
malignant neoplasms.
Cyclosphosphamide

The original rationale that guided its molecular design was

twofold. First, if a cyclic phosphamide group replaced the N-
methyl of mechlorethamine, the compound might be relatively
inert, presumably because the bis-(2-chloroethyl) group of the
molecule could not ionize until the cyclic phosphamide was
cleaved at the phosphorous-nitrogen linkage.
Second, it was hoped that neplastic tissues might posses
phosphatase of phosphamidase activity capable of
accomplishing this cleavage, thus resulting in the selective
production of an activated nitrogen mustard in the malignant
cells.
Synthesis of Cyclophosphamide
Polyfunctional Alkylating Drugs: S.A.R.
Genotoxic carcinogens, able to damage DNA by
alkylation reactions, represent a very diverse
class of agents which are capable of producing a
wide range of DNA modifications.
The mechanisms leading to genetic changes as a
result of exposure to alkylating agents (AAs)
have been studied in male germ cells of
Drosophila using a structure-activity relationship
approach (SAR).
The analytical tools available concern both genetic
and molecular assays.
Pharmacological Effects: Polyfunctional Alkylating Drugs
Injection site damage (vesicant effects) and systemic
toxicity.
- Toxicity is dose related;
- Primarily affects the rapidly dividing cells of bone
marrow, GI tract. Nausea vomiting occurs within a hour
with Mechlorethamine, Carmustine and
Cyclophosphamide.
- Cyclophosphamide cytotoxicity depends on activation
by microsomal enzyme system.
- Hepatic microsomal P450 mixed-function oxidase
catalyzes conversion of cyclophosphamide to the active
forms: 4- hydroxycyclophosphamide and
aldophosphamide.
Synthesis of Busulphan
Miscellaneous : Cisplatin.
(Alkylating-like)
Platinum-based chemotherapeutic drugs (termed
platinum analogues) act in a similar manner. These
agents do not have an alkyl group, but nevertheless
damage DNA. They permanently coordinate to DNA
to interfere with DNA repair, so they are sometimes
described as "alkylating-like".
Platinum
– Cisplatin
– Carboplatin
– Oxaliplatin
These agents also bind at N7 of guanine.
Alkylating Agent Toxicity: Summary
• IV mechlorethamine, cyclophosphamide,
carmustine: Nausea and Vomiting (common)
• Oral cyclophosphamide: Nausea and Vomiting
(less frequently)
• Most Important Toxic Effect: Bone marrow
suppression, leukopenia, thrombocytopenia
o secondary to myelosuppression --
severe infection
septicemia
o hemorrhage
• Cyclophosphamide : Alopecia, hemorrhagic
cystitis (may be avoided by adequate hydration).
Nitrosourea Cross-Linking
Antineoplastic agents
– Cyclophosphamide
– Uramustine or uracil mustard
– Chlorambucil
Antineoplastic agents: Cyclophosphamide-
MOA
Cyclophosphamide is biotransformed
principally in the liver to active alkylating
metabolites by a mixed function
microsomal oxidase system. These
metabolites interfere with the growth of
susceptible rapidly proliferating malignant
cells. The mechanism of action is thought
to involve cross-linking of tumor cell DNA.
Metabolism of Cyclophosphamide
Indications and Usage for Cyclophosphamide
Malignant Diseases
• Malignant lymphomas (Hodgkin’s disease,
lymphocytic lymphoma (nodular or diffuse), mixed-
cell type lymphoma
• Multiple myeloma.
• Leukemias
• Neuroblastoma .
• Adenocarcinoma of the ovary.
• Retinoblastoma.
• Carcinoma of the breast.
Nonmalignant Disease
Biopsy Proven “Minimal Change” Nephrotic Syndrome
in Children
•2070/02/09
Chlorambucil
MOA: Chlorambucil is extensively metabolized in
the liver primarily to phenylacetic acid mustard,
which has antineoplastic activity. Chlorambucil
and its major metabolite spontaneously degrade
in vivo forming monohydroxy and dihydroxy
derivatives.
Uses:
Indicated in the treatment of chronic lymphatic
(lymphocytic) leukemia, malignant lymphomas
including lymphosarcoma, giant follicular
lymphoma, and Hodgkin’s disease.
Hodgkin Lymphoma- which is a
cancer originating from white
blood cells called lymphocytes.
Non-Hodgkin lymphomas (NHLs) are
a diverse group of blood cancers
that include any kind of lymphoma
except Hodgkin's lymphomas.
Adverse Reactions
Hematologic: The most common side effect is bone marrow
suppression, anemia, leucopenia, neutropenia and
thrombocytopenia.
Gastrointestinal: Gastrointestinal disturbances such as nausea
and vomiting, diarrhea, and oral ulceration occur infrequently.
CNS: Tremors, muscular twitching, myoclonia, confusion,
agitation, ataxia, flaccid paresis, and hallucinations have been
reported as rare adverse experiences to chlorambucil which
resolve upon discontinuation of drug.
Dermatologic: Allergic reactions such as urticaria and
angioneurotic edema have been reported following initial or
subsequent dosing.
Miscellaneous: Other reported adverse reactions include:
pulmonary fibrosis, hepatotoxicity and jaundice, drug fever,
peripheral neuropathy, interstitial pneumonia, sterile cystitis,
infertility, leukemia, and secondary malignancies.
Chlorambucil
Remedy of side-effects
- these affect less than
Approach to be comfortable
1 in 10 patient who
take Chlorambucil
Eat little and often. Stick to
Feeling or being sick
simple foods.
Patient has to take plenty of
Diarrhea
water to replace lost fluids.
Brushing the teeth 2-3 times a day
with a soft toothbrush and regularly
Mouth ulcers
using a mouth rinse may help to
prevent this.
 Uramustine or uracil mustard

Uramustine (Chemically it is a derivative of nitrogen

mustard and uracil) is used in lymphatic
malignancies such as non-Hodgkin's lymphoma. It
works by damaging DNA, primarily in cancer cells
that preferentially take up the uracil due to their
need to make nucleic acids during their rapid cycles
of cell division.
The DNA damage leads to apoptosis of the affected
cells. Bone marrow suppression and nausea are the
main side effects.
Busulphan

Busulfan is a cell cycle non-specific

alkylating antineoplastic agent, in
the class of alkyl sulfonates. Its
chemical designation is 1,4-
butanediol dimethanesulfonate.
Busulphan: MOA
Its mechanism of action through alkylation
produces guanine-adenine intrastrand
crosslinks. This occurs through an SN2
reaction in which the relatively
nucleophilic guanine N7 attacks the carbon
adjacent to the mesylate leaving group.
This kind of damage cannot be repaired by
cellular machinery and thus the cell
undergoes apoptosis.
Mode of action of Busulfan: Summary
Its mechanism of action through alkylation produces
DNA-DNA and DNA-protein cross linking. The
resulting covalent bonds inhibit DNA, RNA, and
protein synthesis. The inhibition of DNA synthesis
subsequently produces a cytotoxic effect.
Busulfan is a bifunctional alkylating agent in which
two labile methanesulfonate groups are attached to
opposite ends of a 4-carbon alkyl chain. In aqueous
media, busulfan hydrolyzes to release the
methanesulfonate groups. This produces reactive
carbonium ions that can alkylate DNA. DNA damage
is thought to be responsible for much of the
cytotoxicity of busulfan.
Cisplatin
Non-platinum Antitumor complexes

Titanocene dichloride
Miscellaneous : Cisplatin. Mechanism of Action.
Cisplatin, carboplatin, and oxaliplatin
enter cells by diffusion, and by an
active Cu2+ transporter . Inside the cell,
the chloride atoms of cisplatin may be
displaced and the compound may be
inactivated directly by reaction with
nucleophiles such as thiols. Chloride is
replaced by water, yielding a positively
charged molecule.
Miscellaneous : Cisplatin. Mechanism of Action.
In the primary cytotoxic reaction, the aquated
species of the drug then reacts with nucleophilic
sites on DNA and proteins. Aquation is favored
at the low concentrations of chloride inside the
cell and in the urine.
High concentrations of chloride stabilize the drug,
explaining the effectiveness of chloride diuresis
in preventing nephrotoxicity (see below).
Hydrolysis of carboplatin removes the bidentate
cyclobutanedicarboxylato group; this activation
reaction occurs slowly.
Mechanism of action: Summary
Following administration, one of the chloride
ligands is slowly displaced by water (an aqua
ligand), in a process termed aquation. The aqua
ligand in the resulting [PtCl(H2O)(NH3)2]+ is itself
easily displaced, allowing the platinum atom to
bind to bases.
Of the bases on DNA, guanine is preferred.
Subsequent to formation of [PtCl(guanine-
DNA)(NH3)2]+, cross linking can occur via
displacement of the other chloride ligand,
typically by another guanine.
INDICATIONS
Cisplatin injection is indicated as
therapy to be employed as follows:
1. Metastatic Testicular Tumors
2. Metastatic Ovarian Tumors
3. Advanced Bladder Cancer
Antineoplastic agents: Cisplatin - Synthesis
Cisplatin has a number of side-effects that can limit its use:
1. Nephrotoxicity (kidney damage) is a major concern.
2. Neurotoxicity (nerve damage) can be anticipated by
performing nerve conduction studies before and after
treatment.
3. Nausea and vomiting: cisplatin is one of the most
emetogenic chemotherapy agents, but this symptom is
managed with prophylactic antiemetics (ondansetron,
granisetron, etc.)
In combination with corticosteroids. Aprepitant combined
with ondansetron and dexamethasone has been shown
to be better for highly emetogenic chemotherapy than
just ondansetron and dexamethasone.
4. Ototoxicity (hearing loss): unfortunately there is at
present no effective treatment to prevent this side
effect, which may be severe.
Antimetabolites
Antimetabolites: Azothioprine.

Azathioprine is a pro-drug. Following oral ingestion, it is

metabolized into the active 6-mercaptopurine, itself a
purine synthesis inhibitor.
6-Mercaptopurine impedes DNA synthesis and thus
inhibits the proliferation of cells, especially the fast-
growing lymphocytes.
T-cells and B-cells are particularly affected by the
inhibition of purine synthesis.
Azathioprine is an effective drug used alone in certain
autoimmune diseases, or in combination with other
immunosuppressant in organ transplantation.
Metabolic pathway for azathioprine
Antimetabolites: Mercaptopurine

DOSAGE AND ADMINISTRATION

The usual daily maintenance dose of
Mercaptopurine is 1.5 to 2.5 mg/kg/day as a
single dose.
Antimetabolites
Anticancer Agents:Antimetabolites
Folic Acid Methotrexate

5-Flurouracil
Uracil
Mode of action of Antimetabolites
Antimetabolites can be used in cancer
treatment, as they interfere with DNA
replication and therefore cell division
and the growth of tumors. Because
cancer cells spend more time dividing
than other cells, inhibiting cell division
harms tumor cells more than other
cells.
Anti-metabolites designed as purine (azathioprine,
mercaptopurine) or pyrimidine - which become
the building blocks of DNA. They prevent these
substances becoming incorporated in to DNA
during the S phase (of the cell cycle), stopping
normal development and division.
They also affect RNA synthesis. However, because
thymidine is used in DNA but not in RNA (where
uracil is used instead), inhibition of thymidine
sythesis via thymidylate synthase selectively
inhibits DNA synthesis over RNA synthesis.
The mechanism of action of 5-Fluorouracil
5-Fu – a widely used antagonist of pyrimidines.
Like the other pyrimidine antagonists, 5-Fluorouracil
resembles the structure of the normal molecule. It
functions as an inhibitor of DNA synthesis both by
blocking the formation of normal pyrimidine
nucleotides by inhibiting the enzyme, and by
engaging in DNA synthesis after turning into a
growing DNA molecule.
Folate Antagonists
Folate antagonists, also known as antifolates,
inhibit dihydrofolate reductase (DHFR), an
enzyme involved in the formation of
nucleotides.
When this enzyme is blocked, nucleotides are not
formed, disrupting DNA replication and cell
division. Methotrexate is the primary folate
antagonist used as a chemotherapeutic agent. It
may be used alone or in combination with other
anticancer drugs.
Mode of action of Methotraxate
Methotrexate competitively and reversibly inhibits
dihydrofolate reductase (DHFR), an enzyme that
participates in the tetrahydrofolate synthesis.
The affinity of methotrexate for DHFR is about one
thousand-fold that of folate for DHFR. Dihydrofolate
reductase catalyses the conversion of dihydrofolate
to the active tetrahydrofolate.
Folic acid is needed for the de novo synthesis of the
nucleoside thymidine, required for DNA synthesis.
Also, folate is needed for purine base synthesis, so
all purine synthesis will be inhibited.
Methotrexate, therefore, inhibits the synthesis of
DNA, RNA, thymidylates, and proteins.
Lower doses of methotrexate have been shown to
be very effective for the management of
rheumatoid arthritis and psoriasis.
In these cases inhibition of dihydrofolate
reductase (DHFR) is not thought to be the main
mechanism, rather the inhibition of enzymes
involved in purine metabolism, leading to
accumulation of adenosine, or the inhibition of T
cell activation and suppression of intercellular
adhesion molecule expression by T cells.
Methotraxate: Synthesis
The purine antagonists (like Mercaptopurine)
function by inhibiting DNA synthesis in two
different ways:
1. They can inhibit the production of the purine
containing nucleotides, adenine and guanine. If
a cell doesn't have sufficient amounts of
purines, DNA synthesis is halted and the cell
cannot divide.
2. They may be incorporated into the DNA
molecule during DNA synthesis. The presence
of the inhibitor is thought to interfere with
further cell division.
Mercaptopurine
Mercaptopurine (also called 6-Mercaptopurine) is
an immunosuppressive drug used to treat
leukemia.
It is also used for pediatric non-Hodgkin's
lymphoma, polycythemia vera, (erythremia,
occurs when excess red blood cells are produced
as a result of an abnormality of the bone
marrow) psoriatic arthritis, and inflammatory
bowel disease (such as ulcerative colitis).
Mode of action of 5-fluorocytosine
As a pyrimidine analogue, it is
transformed inside the cell into
different cytotoxic metabolites which
are then incorporated into DNA and
RNA, finally inducing cell cycle arrest
and apoptosis by inhibiting the cell's
ability to synthesize DNA.
5-Flurouracil
Methotrexate

Folic acid antagonist: Methotrexate.

Pyrimidine antagonist: 5-Fluorouracil, Foxuridine,
Cytarabine, Capecitabine, and Gemcitabine.
Purine antagonist: 6-Mercaptopurine and 6-Thioguanine.
Adenosine deaminase inhibitor: Cladribine, Fludarabine
and Pentostatin.
Methotrexate – MOA: is thought to affect cancer and
rheumatoid arthritis by two different pathways. For
cancer, methotrexate allosterically inhibits
dihydrofolate reductase (DHFR), an enzyme that
participates in the tetrahydrofolate synthesis.
The affinity of methotrexate for DHFR is about one
thousand-fold that of folate. DHFR catalyses the
conversion of dihydrofolate to the active
tetrahydrofolate.
Folic acid is needed for the de novo synthesis of the
nucleoside thymidine, required for DNA synthesis.
Also, folate is needed for purine base synthesis, so
all purine synthesis will be inhibited. Methotrexate,
therefore, inhibits the synthesis of DNA, RNA,
thymidylates, and proteins.
Natural products
Antitumor compounds
• Antibiotics: Doxorubicin,
Mitomycin.
• Plant products : Etoposide,
Vincristine,Vinblastine, Taxol.
Natural products Antitumor compounds
1. Spindle poison/mitotic inhibitor: Taxenes
(Taxol,Docitaxel) and Vinca Alkaloids- Vinblastine
,Vincristine.
2. Cytotoxic/antitumor antibiotics -Anthracycline
family: (Daunorubicin, Doxorubicin and
streptomyces (Actinomycin, Bleomycin, Mitomycin).
3. Topoisomerase inhibitors –
Podophyllum:(Etoposide, Teniposide).
4. Monoclonal antibodies - Receptor tyrosine
kinase(Cetuximab) - CD20 (Rituximab,
• 3.5. Biological Response modifiers – Interferon.
Mode of action mitotic poison (Tubulin inhibitor)
Taxol and vinca alkaloids work by interfering
with normal microtubule breakdown
during cell division.
Together with docetaxel, it forms the drug
category of the taxanes.Tubulin is a
structural protein which polymerises to
form microtubules.
The cell cytoskeleton and mitotic spindle,
amongst other things, are made of
microtubules.
Antineoplastic agents: Natural Products

Anticancer Agents: Natural Products

Taxol Vincristine
Difference between the mode of action of
Vincrastine and Taxol
Vincrastine work by preventing mitosis in
metaphase. These alkaloids bind to
tubulin, thus preventing the cell from
making the spindles it needs to be able to
divide.
Where as taxol which interferes with cell
division by keeping the spindles from being
broken down.
Antineoplastic agents

Anticancer Agents: Natural Products

Taxus Baccata -L
Taxol is a potent compound that targets rapidly
dividing cancer cells and prevents them from
replicating. A large number of microtubules are
formed at the start of cell division, and as cell
division comes to an end, these microtubules are
normally broken down into tubulin.
Taxol binds to the microtubules and inhibits their
depolymerization into tubulin.
This means that Taxol blocks a cell's ability to break
down the mitotic spindle during mitosis (cell
division).
With the spindle still in place the cell can't divide into
daughter cells and therefore the cancer can’t
spread.
TAXOL (paclitaxel) is
obtained via a semi-
synthetic process from
Taxus baccata. The
chemical name for
paclitaxel is 5β,20-
Epoxy-
1,2α,4,7β,10β,13α-
hexahydroxytax-11-en-
9-one 4,10-diacetate 2-
benzoate 13-ester with
(2R,3S)-N-benzoyl-3-
phenylisoserine.
MOA
Paclitaxel is a novel antimicrotubule agent that
promotes the assembly of microtubules from
tubulin dimers and stabilizes microtubules by
preventing depolymerization.
This stability results in the inhibition of the normal
dynamic reorganization of the microtubule
network that is essential for vital interphase and
mitotic cellular functions.
In addition, paclitaxel induces abnormal arrays or
“bundles” of microtubules throughout the cell
cycle and multiple asters of microtubules during
mitosis.
Taxol: Properties
Paclitaxel is a white to off-white crystalline
powder with the empirical formula
C47H51NO14 and a molecular weight of 853.9. It
is highly lipophilic, insoluble in water, and melts
at around 216–217° C.
Dosage:
a. TAXOL administered intravenously over 3 hours
at a dose of 175 mg/m2 followed by cisplatin at
a dose of 75 mg/m2; or
b. TAXOL administered intravenously over 24
hours at a dose of 135 mg/m2 followed by
cisplatin at a dose of 75 mg/m2.
TAXOL (paclitaxel) Injection is a clear, colorless to
slightly yellow viscous solution. It is supplied as
a nonaqueous solution intended for dilution
with a suitable parenteral fluid prior to
intravenous infusion.
TAXOL is available in 30 mg (5 mL), 100 mg (16.7
mL), and 300 mg (50 mL) multidose vials. Each
mL of sterile nonpyrogenic solution contains 6
mg paclitaxel, 527 mg of purified Cremophor®
EL* (polyoxyethylated castor oil) and 49.7% (v/v)
dehydrated alcohol, USP.
Stability
Unopened vials of TAXOL (paclitaxel) Injection are
stable until the date indicated on the package when
stored between 20°–25° C (68°–77° F), in the
original package. Neither freezing nor refrigeration
adversely affects the stability of the product.
Upon refrigeration, components in the TAXOL vial may
precipitate, but will redissolve upon reaching room
temperature with little or no agitation.
There is no impact on product quality under these
circumstances. If the solution remains cloudy or if
an insoluble precipitate is noted, the vial should be
discarded.
TAXOL is a prescription medicine used to treat
some forms of:
• ovarian cancer
• breast cancer
• lung cancer
• Kaposi’s sarcoma

It is not known if TAXOL is safe or

effective in children.
Kaposi's sarcoma

Intraoral AIDS-associated Kaposi sarcoma

with an overlying candidiasis infection
Kaposi's sarcoma before Interferon treatment
Taxotere (docetaxel) Injection Concentrate
Indications:
• Breast Cancer
• Advanced Non-Small Cell Lung Cancer.
• Metastatic Androgen-Independent
Prostate Cancer
• Advanced Gastric/GE Junction Cancer
Locally Advanced Head and Neck Cancer
Formulations and compositions: Taxoter (Docetaxel)
Docetaxel is a white powder and is the active
ingredient available in 20 mg and 80 mg Taxotere
single-dose vials of concentrated anhydrous
docetaxel in polysorbate 80.
The solution is a clear brown-yellow containing 40 mg
docetaxel and 1040 mg polysorbate 80 per mL.
20 mg Taxotere is distributed in a blister carton
containing one single-dose vial of Taxotere
(docetaxel) preparation in 0.5 mL sterile pyrogen -
free anhydrous polysorbate 80, and a single dose
Taxotere solvent vial containing 1.5 mL 13% ethanol
in saline to be combined and diluted in a 250 mL
infusion bag containing 0.9% sodium chloride or 5%
glucose for administration.
Taxotere (Docetaxel)
TAXOL Taxotere
Antineoplastic agents
Antineoplastic agents: Vinca Alkaloids
Catharanthus roseus
Anthracyclines
Mode of action of Mitomycin
Mitomycin C is a potent DNA crosslinker. A
single crosslink per genome has shown to
be effective in killing bacteria.
This is accomplished by reductive
activation, followed, by two N-
alkylations.
Both alkylations are sequence specific for a
guanine nucleoside in the sequence.
Anthracyclines are:
• Daunorubicin
• Daunorubicin (liposomal)
• Doxorubicin
• Doxorubicin (liposomal)
• Epirubicin
• Idarubicin
• Mitoxantrone
Doxorubicin hydrochloride
Daunorubicin

Idarubicin Epirubicin
Mode of action of Doxorubicin
The exact mechanism of action of doxorubicin is
complex and still somewhat unclear, though it is
thought to interact with DNA by intercalation as
demonstrate in previous slide.
Doxorubicin is known to interact with DNA by
intercalation and inhibition of macromolecular
biosynthesis.
This inhibits the progression of the enzyme
topoisomerase II, which unwinds DNA for
transcription.
Doxorubicin stabilizes the topoisomerase II complex
after it has broken the DNA chain for replication,
preventing the DNA double helix from being
resealed and thereby stopping the process of
replication.
Doxorubicin
hydrochloride
Doxorubicin – Analogues:
Chemically, Doxorubicin
hydrochloride is
(8S,10S)-10-[(3-Amino-
2,3,6-trideoxy-α-L-lyxo-
hexopyranosyl) - oxy] - 8
- glycoloyl - 7,8,9,10 -
tetrahydro - 6,8,11 -
trihydroxy - 1 - methoxy
- 5,12 -
naphthacenedione
hydrochloride. The
structural formula is as
follows:
Doxorubicin – MOA:
Doxorubicin interacts with DNA by intercalation
and inhibition of macromolecular biosynthesis.
This inhibits the progression of the enzyme
topoisomerase II, which relaxes supercoils in
DNA for transcription.
Doxorubicin stabilizes the topoisomerase II
complex after it has broken the DNA chain for
replication, preventing the DNA double helix
from being resealed and thereby stopping the
process of replication.
Diagram of two Doxorubicin molecules intercalating DNA
Indications and Usage for Doxorubicin
Doxorubicin Hydrochloride Injection, has been used
successfully to produce regression in disseminated
neoplastic conditions such as acute lymphoblastic
leukemia, acute myeloblastic leukemia, Wilms’
tumor, neuroblastoma, soft tissue and bone
sarcomas, breast carcinoma, ovarian carcinoma,
transitional cell bladder carcinoma, thyroid
carcinoma, gastric carcinoma, Hodgkin’s disease,
malignant lymphoma, and bronchogenic carcinoma
in which the small cell histologic type is the most
responsive compared to other cell types.
Doxorubicin - Dosage:
The most commonly used dose
schedule when used as a single
agent is 60 to 75 mg/m2 as a single
intravenous injection administered
at 21-day intervals.
Liposomal formulations
Doxorubicin (Doxil) is a pegylated (polyethylene
glycol coated) liposome-encapsulated form of
doxorubicin formerly made by Ben Venue
Laboratories in the United States for Janssen
Products, a subsidiary of Johnson & Johnson.
It was developed to treat Kaposi's sarcoma, an
AIDS-related cancer that causes lesions to grow
under the skin, in the lining of the mouth, nose
and throat, or in other organs.
The polyethylene glycol coating results in
preferential concentration of Doxil in the skin.
MOA:
The anthracyclines exert their cytotoxic action
through four major mechanisms. These are
(1) Inhibition of topoisomerase II;
(2) High-affinity binding to DNA through intercalation,
with consequent blockade of the synthesis of DNA
and RNA, and DNA strand scission;
(3) Binding to cellular membranes to alter fluidity and
ion transport; and
(4) Generation of semiquinone free radicals and
oxygen free radicals through an iron-dependent,
enzyme-mediated reductive process. This free
radical mechanism has been established to be the
cause of the cardiotoxicity associated with the
anthracyclines.
Etoposide
Mechanism of Action
Etoposide forms a ternary complex with DNA and the
topoisomerase II enzyme, preventing re-ligation of the
DNA strands.
This causes errors in DNA synthesis and promotes
apoptosis of the cancer cell.
Etoposide's main effect appears to be at the G 2 portion
of the cell cycle. At high concentrations (10 mcg/mL or
more), lysis of cells entering mitosis is seen; at low
concentrations (0.3 to 10 mcg/mL), cells are inhibited
from entering prophase. Predominant macromolecular
effect appears to be DNA synthesis inhibition.
Etoposide
Hormones : Mitotane

MOA:
Mitotane alters steroid peripheral
metabolism, directly suppresses
the adrenal cortex and alters
cortisone metabolism leading to
hypocortisolism.
Indication: Mitotane
Mitotane is used to treat cancer of the adrenal glands.
The adrenal glands produce hormones, which are
needed by the body to deal with stress, fight
infection, and maintain normal functions such as
blood pressure.
Certain cancers cause the adrenal glands to produce
too much cortisol and other hormones, causing a
certain serious condition (Cushing's syndrome).
Too much of these hormones can cause many
problems such as blood pressure changes, weight
changes, muscle/bone weakness, thinning skin, and
diabetes.
Hormones : Mitotane: ADRs
• loss of appetite
• nausea
• vomiting
• diarrhea
• depression
• lack of energy
• unusual drowsiness
• feeling that the room is spinning
• changes in vision
• rash or changes in skin color
Hormones : Tamoxifen.
Hormones - Tamoxifen: MOA
Tamoxifen competitively binds to estrogen
receptors on tumors and other tissue targets,
producing a nuclear complex that decreases
DNA synthesis and inhibits estrogen effects.
It is a nonsteroidal agent with potent
antiestrogenic properties which compete with
estrogen for binding sites in breast and other
tissues. Tamoxifen causes cells to remain in the
G0 and G1 phases of the cell cycle.
Because it prevents (pre)cancerous cells from
dividing but does not cause cell death,
tamoxifen is cytostatic rather than cytocidal.
Antineoplastic agents: Tamoxifen
Tamoxifen is given orally and is rapidly and
completely absorbed. High plasma levels of
tamoxifen are obtained within 4-6 hours after
oral administration, and the agent has a much
longer biologic half-life than estradiol - on the
order of 7-14 days.
It is extensively metabolized by the liver P450
system, and the main metabolites also possess
antitumor activity similar to that of the parent
drug. Tamoxifen is well tolerated, and its side
effects are generally quite mild
 Synthesis of Tamoxifen

Phenyl Magnesium
bromide

Dehydration

4- -Dmethylaminoethoxy
Tamoxifen
--ethyldeoxybenzoin 1(4- -Dmethylaminoethoxyphenyl)
1,2-diphenyl butanol
Metabolism of Tamoxifen
Tamoxifen itself is a prodrug, having relatively little
affinity for its target protein, the estrogen receptor.
It is metabolized in the liver by the cytochrome
P450 (isoform CYP2D6 and CYP3A4) into active
metabolites such as 4-hydroxytamoxifen
(afimoxifene) and N-desmethyl-4-hydroxytamoxifen
(endoxifen) which have 30-100 times more affinity
with the estrogen receptor than tamoxifen itself.
These active metabolites compete with estrogen in
the body for binding to the estrogen receptor.
In breast tissue, 4-hydroxytamoxifen acts as an
estrogen receptor antagonist so that transcription
of estrogen-responsive genes is inhibited.
Interferon
alfa-2a and
alfa-2b
Biological Response modifiers – Interferon.
Interferons assist the immune response by
inhibiting viral replication within host cells,
activating natural killer cells and macrophages,
increasing antigen presentation to lymphocytes,
and inducing the resistance of host cells to viral
infection.
When the antigen is presented to matching T and
B cells, those cells multiply and strategically and
specifically wipe out the foreign substance.
That is why antigen presentation is so important
to the immune response.
In Other words:
Interferons are proteins made and
released by host cells in response to
the presence of pathogens such as
viruses, bacteria, parasites or tumor
cells.
They allow for communication between
cells to trigger the protective defenses
of the immune system that eradicate
pathogens or tumors.
Interferon alfa-2a: MOA
Interferon alfa-2a has
antiproliferative and
immunomodulatory activities.
Its elimination half-life is 3.7 to
8.5 h after IV infusion.
Interferon alfa-2a is a long acting
interferon. Interferons are proteins
released in the body in response to
viral infections.
Interferons are important for
fighting viruses in the body, for
regulating reproduction of cells,
and for regulating the immune
system.
Interferon alfa-2a : Indication
Interferon alfa-2a is used to treat
chronic hepatitis C, hairy cell
leukemia, AIDS-related Kaposi's
sarcoma, and some types of
chronic myelogenous leukemia
(CML).
Interferon alfa-2a : Dosage
Usual Adult Dose for Chronic Myelogenous Leukemia:
9 million IU daily subcutaneously or IM.
Usual Adult Dose for Hairy Cell Leukemia:
Induction dose: 3 million IU daily subcutaneously or
IM for 16 to 24 weeks.
Maintenance dose: 3 million IU three times a week
for up to 24 consecutive months.
Usual Adult Dose for Kaposi's Sarcoma:
Induction dose: 36 million IU daily subcutaneously or
IM for 10 to 12 weeks.
Maintenance dose: 36 million intl units three times
a week.
Interferon alfa-2b : Indication
It is treatment of chronic hepatitis C, chronic
hepatitis B, hairy cell leukemia, chronic
myelogenous leukemia, multiple myeloma,
follicular lymphoma, carcinoid tumor, and
malignant melanoma.
Interferon Alfa-2b: MOA
Inhibition of virus replication in
virus-infected cells, and
suppression of cell proliferation,
and immunomodulating activities
such as enhancement of phagocytic
activity of macrophages and
augmentation of specific
cytotoxicity of lymphocytes for
target cells.
Interferon Alfa-2b: Dosage and Administration
• AIDS-Related Kaposi Sarcoma: Adults
IM or Subcutaneous 30 million units/m 2 per dose 3 times/wk
until disease progression or maximal response has been
achieved after 16 wk of treatment. Dose reduction is
frequently required.
• Hairy Cell Leukemia: Adults
IM or Subcutaneous 2 million units (million units)/m 2 3
times/wk for up to 6 months. Patients with platelet counts of
less than 50,000/mm 3 should receive the drug by
subcutaneous administration and not IM.
• Malignant Melanoma: Adults – IV: Induction
20 million units/m 2 infused over 20 minutes, 5 consecutive
days/wk, for 4 wk.
• Maintenance
Subcutaneous administration of 10 million units/m 2 3 times/wk
for 48 wk.
Antineoplastic
agents: ADRS
1. Alopecia
2. Severe Vomiting
3. Myelosuppression
Alopecia
Hair follicles are one of the fast
replicating cells of the body. So
in the first line they suffers.
Severe Vomiting
It is now widely known that
cytotoxic chemotherapeutic
agents rapidly proliferating
gastric mucosa and cause a
detectable increase in
blood levels of serotonin
(5-HT) CTZ causing severe
vomiting.
Antineoplastic agents: ADRS
Myelosuppression
The bone marrow is the thick liquid in the inner part
of some bones that produces white blood cells
(WBCs), red blood cells (RBCs), and platelets. One of
the most common side effects of chemotherapy is
short-term damage to the bone marrow.
Cells are constantly produced and grow rapidly in the
bone marrow. As a result, they are sensitive to the
effects of chemotherapy. Until the bone marrow
cells recover from chemotherapy damage, patient
may have abnormally low numbers of WBCs, RBCs,
and/or platelets. This is called bone marrow
suppression or myelosuppression.
Myelosuppression: Symptoms
Fatigue: This results from a shortage of red blood
cells. It is also known as Anemia.
-- Bleeding: This results from a shortage of
platelets. It is also known as Thrombocytopenia.
-- Infection risk: This results from a shortage of
white blood cells, notably neutrophils. It is also
known as Neutropenia.
All of these conditions can be considered a result
of myelosuppression.
Cancer in the ‘Developed’ World
1900: 1 in 25
•1925: 1 in 10
•1960: 1 in 4
•2000: 1 in 3
Cancer and food
Cancer and foods
Society cannot ran away from this deadly
pathology- Cancer but can managed it
comfortably.
It is very difficult to evaluate the beneficial or
harmful constituents of foods because of
collective consumption. But we have the idea
what we should eat to avoid the odds of having
this disease. The diet should be high enough
with green leafy vegetables, legumes such as
peas and beans and fresh fruits.
Anti-oxidants and cancer
Oxidation is the chemical process that causes
metal to rust and apples to turn brown. When
this same process happens inside our body, it
can harm cells and tissues.
Primarily, molecules called free radicals are
responsible for this oxidative damage.
Free radicals can be contained in (or induced to
form by) a variety of things including tobacco
smoke, radiation (like sunlight or x-rays) and
even the normal functioning of the human body.
Organic Foods
Avoid or limit:
• „Charred foods (burnt meat etc)
• Red meat
• „Sugar
• „Heavily salted, smoked or pickled foods
• „Sodas and soft drinks
• „Alcohol
• „Additives like Saccharine, aspartame
• „Farmed fish
Plastics
• †NEVER microwave food in plastic
• †Avoid PVC products
• †Get rid of Teflon
• †Store foods in glass or metal
• † Avoid canned foods (BPA) –a
bisphenol carcinogenic
The cabbage, cauliflowers and broccoli
containing dithiothiones are very
useful to neutralize the free radical -
carcinogens in biosystem.
Polyhydroxy compounds of different
varieties of tea and natural β –
carotine suppose to be the best free
radical neutralizing foods.
Cancer and Foods

Cancer Introduction: Fruit market in Spain

Cancer and Foods

Cancer Introduction: Vegetables in Lasha

Asparagus
Cancer and Foods
The worst devil of our food is saturated
fat from the delicious mutton, pork,
beef, duck and goose and animal origin
fat as well the comfortable and
imaginable urban life with no any step
of walking and lack of exercise.
Cancer and Foods
Cigarettes are proven to be highly addictive, as
well as a cause of multiple types of cancer, heart
disease, respiratory disease, circulatory disease,
birth defects (which include mental and physical
disability) and emphysema.
Acetaldehyde – a metabolite of alcoholic beverage
- is toxic, an irritant, and a carcinogen. Salt and
sugars are slow poisons. The mixing of smoking
with alcohol thought to be the potent mix for
tumor initiation.
Cancer and Foods: Anthocyanin
Berries
Cancer and Foods: Berry and grapes
Cancer and Foods: Green Tea
Cancer and Foods: Curcumin
Cancer and Foods:
Cancer and Foods: Lemon
Cancer and Foods: Pycnogenol
A natural substance extracted from the bark
of pine trees (Pinus pinaster), Pycnogenol
has a molecular structure similar to
compounds found in the family of
flavonoids, known to be powerful
antioxidant agents.
Bioflavonoids, which enhance the function
of vitamin C, are a subgroup of flavonoids.
Cancer and Foods: Pycnogenol (proanthocyanidins)
Pycnogenol is the trade name for a dietary
supplement ingredient made from an extract of
the bark of a pine tree grown in the western
Mediterranean. Pycnogenol contains a family of
natural chemicals called proanthocyanidins,
which are also found in grape seeds, red wine,
apples and green tea. You may find products
containing proanthocyanidins from these
sources also labeled as pycnogenol. Alhough
they vary greatly in their chemical structure, as a
group, proanthocyanidins have antibacterial,
antiviral, anti-inflammatory and antioxidant
properties.
Pycnogenol is a potent antioxidant, with an
antioxidant activity approximately fifty times that
of vitamin C. Because of the chemical structure of
Pycnogenol , it can be incorporated into and
protect both the aqueous (cytoplasmic) and lipid
(cell memrane) phases of cells from damage by free
radicals.
Pycnogenol also promotes increased availability of
vitamin C within the body. Pycnogenol antioxidants
are particularly effective for maintaining healthy
functioning of blood vessels, and the eyes, as well
as maintaining normal strength, flexibility and
suppleness of the skin.
Pycnogenol also helps maintain a normal response
by the body to allergic or inflammatory challenge.
Cancer and Foods
Cancer and Foods: Lycopen
Cancer and Foods
Water melon Red Guava
Cancer and Foods: Grapefruit
Legumes
Peas
Cancer and Foods: Phytoestrogens - Different varieties of Soybeans
Cruciferous Vegetables

The generic structure of a glucosinolate. R - this represents a variety of different

chemistries which are generally classified as aliphatic, indole or aromatic.
Cancer and Foods: Sulforaphane

Brussel
Sprout
Kale
Kale
Winter Squash Cantaloupe
Arugula
Collard Green Horse RADDISH
Kohlrabi Rutabaga Turnip
Cancer and Foods

Brazilnut plant and fruit

Brazil nut with shell
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: Cancers derived from epithelial cells. This group includes
many of the most common cancers, particularly in the aged, and
include nearly all those developing in the breast, prostate, lung,
pancreas, and colon.
Sarcoma: Cancers arising from connective tissue (i.e. bone, cartilage, fat,
nerve), each of which develop from cells originating in mesenchymal
cells outside the bone marrow.
Lymphoma and leukemia: These two classes of cancer arise from
hematopoietic (blood-forming) cells that leave the marrow and tend
to mature in the lymph nodes and blood, respectively.
Germ cell tumor: Cancers derived from pluripotent cells, most often
presenting in the testicle or the ovary (seminoma and dysgerminoma,
respectively.
Blastoma: Cancers derived from immature "precursor" cells or embryonic
tissue. These are also most common in children.
Prevention of Cancer
We can reduce the risk of getting a cancerous
(malignant) tumor by:
• Eating a healthy diet
• Exercising regularly
• Limiting alcohol
• Maintaining a healthy weight
• Minimizing our exposure to radiation and toxic
chemicals
• Not smoking or chewing tobacco
• Reducing sun exposure
Treatment Options
There are a number of treatment options available for cancer.
Treatments plans are developed depending on the type of
cancer, its location, the extent of the cancer and the stage at
which it is diagnosed, and the health and well-being of the
patient. Treatment may be one or more of several different
therapies.
Chemotherapy is the use of anti-cancer of drugs. Anti-cancer drugs
destroy cancer cells by stopping growth or multiplication at
some point in their life cycles. Drugs may be administered
intravenously (into a vein), orally (by mouth), by injection into a
muscle, topically (applied to the skin) or in other ways,
depending on the drug and the type of cancer. Chemotherapy is
often given in cycles of alternating treatment and rest periods.
Radiation Therapy is the treatment of cancer and other diseases
with ionizing radiation. Ionizing radiation destroys cells, or the
genetic material of cells, in the area being treated, thereby
making it impossible for these cells to continue to grow.
Treatment Options ……
Surgery involves removal of the tumor. Sometimes,
surrounding tissue and lymph nodes are also
removed. Surgery can be performed using
conventional instruments or laser.
Hormone Therapy is the use of hormones to change
the way hormones in the body help cancers to
grow.
Biological Therapy (Immunotherapy) makes use of
the body's immune system, either directly or
indirectly, to fight cancer and lessen the side effects
that may be caused by some other cancer
treatments.
Alternative and Complementary Therapy - includes
acupuncture and homeopathy.
Antitumor drugs can be classified
according to their effect on the
mitotic cycle:
1. Cell cycle active, phase specific
2. Cell cycle active, non-phase
specific
3. Non-cell cycle active
Standard chemotherapy regimens include:
1. AT: Adriamycin and Taxotere
2. AC ± T: Adriamycin and Cytoxan, with or without
Taxol or Taxotere
3. CMF: Cytoxan, methotrexate, and fluorouracil
4. CEF: Cytoxan, Ellence, and fluorouracil
5. FAC: fluorouracil, Adriamycin, and Cytoxan
6. CAF: Cytoxan, Adriamycin, and fluorouracil
(The FAC and CAF regimens use the same medicines
but use different doses and frequencies)
7.TAC: Taxotere, Adriamycin, and Cytoxan
8. GET: Gemzar, Ellence, and Taxol
What EPOCH is effective for and why?
EPOCH is used as treatment against a variety of
lymphoma subtypes, all with varying degrees of
efficacy. These subtypes include: Relapsed or
refractory chronic lymphocytic leukemia, some
less-aggressive mantle cell lymphomas, diffuse
large B-cell lymphoma (DLBCL), Burkitt's
lymphoma, AIDS-related B-cell lymphoma,
NK/T-cell lymphomas (noncutaneous peripheral
T-cell lymphomas), and even very rare subtypes,
such as adult T-cell leukemia/lymphoma (ATLL).
Antineoplastic agents