Lecture № 15

Chemotherapy

Abdullaev Dzhumadil, pharmD

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International Medical University
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 Cancer is a disease in which some of the DNA repair genes are involved in fixing damaged DNA.
Cells with mutations in these genes tend to develop
body’s cells grow uncontrollably and spread additional mutations in other genes and changes in their
to other parts of the body. chromosomes, such as duplications and deletions of
chromosome parts. Together, these mutations may cause
the cells to become cancerous.

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 The tumor microenvironment (TME) is the environment around a tumor, including the surrounding blood vessels,
immune cells, fibroblasts, signaling molecules and the extracellular matrix. The tumor and the surrounding
microenvironment are closely related and interact constantly. Tumors can influence the microenvironment by
releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the
immune cells in the microenvironment can affect the growth and evolution of cancerous cells.

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Cancer that spreads from where it started to a distant part
of the body is called metastatic cancer. For many types of
cancer, it is also called stage IV cancer. The process by
which cancer cells spread to other parts of the body is
called metastasis.

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Many different kinds of chemotherapy or chemo drugs are used to
treat cancer – either alone or in combination with other drugs or
treatments. These drugs are very different in their chemical
composition (what they are made of), how they are prescribed and
given, how useful they are in treating certain types of cancer, and the
.
side effects they might have Every time any new cell is formed, it
goes through a usual process to become a fully functioning (or
mature) cell. The process involves a series of phases and is called the
cell cycle.
Chemotherapy drugs target cells at different phases of the cell cycle.
Understanding how these drugs work helps doctors predict which
drugs are likely to work well together. Doctors can also plan how
often doses of each drug should be given based on the timing of the
cell phases.
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Cancer cells tend to form new cells more quickly than normal
cells and this makes them a better target for chemotherapy
drugs. However, chemo drugs can’t tell the difference
between healthy cells and cancer cells. This means normal
cells are damaged along with the cancer cells, and this causes
side effects. Each time chemo is given, it means trying to find
a balance between killing the cancer cells (in order to cure or
control the disease) and sparing the normal cells (to lessen
side effects).
The good news is that most normal cells will recover from the
effects of chemo over time. But cancer cells are mutated (not
normal) cells, and they usually do not recover from the effects
of chemo. This is why chemo is good at killing many types of
cancer cells.
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 Class of Chemo drugs
Alkylating agents - platinum compounds and nitrosoureas. 
Antimetabolites
Anthracyclines
Anthimicrotubula agents- vinca alkaloids
and taxanes.
Topoisomerase inhibitors
Anti-tumor antibiotics Anthracyclines
Corticosteroids
Other chemotherapy drugs

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 Alkylating agents
Alkylating agents keep the cell from reproducing
(making copies of itself) by damaging its DNA. These
drugs work in all phases of the cell cycle and are used to
treat many different cancers, including cancers of the
lung, breast, and ovary as well as leukemia, lymphoma,
Hodgkin disease, multiple myeloma, and sarcoma.
Because these drugs damage DNA, they can affect the
cells of the bone marrow which make new blood cells. In
rare cases, this can lead to leukemia. The risk of leukemia  Altretamine.  Carmustine.
from alkylating agents is “dose-dependent,” meaning that  Bendamustine.  Chlorambucil.
the risk is small with lower doses, but goes up as the total  Busulfan.  Cisplatin.
amount of the drug used gets higher. The risk of leukemia  Carboplatin.  Cyclophosphamide.
after getting alkylating agents is highest about 5 to 10
years after treatment.
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 Platinum compounds
Platinum-based antineoplastic drugs (informally
called platins) are chemotherapeutic agents used
to treat cancer. They are coordination complexes
of platinum. These drugs are used to treat almost
half of people receiving chemotherapy for cancer.
In this form of chemotherapy, commonly used
drugs include cisplatin, oxaliplatin, and
carboplatin, but several have been proposed or are
under development. Addition of platinum-based
chemotherapy drugs to chemoradiation in women
with early cervical cancer seems to improve
survival and reduce risk of recurrence

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 Cisplatin Trade Name: Platinol® injectable solution 1mg/mL

The mechanism of action of cisplatin has

been associated with ability to crosslink with
the urine bases on the DNA to form DNA
adducts, preventing repair of the DNA
leading to DNA damage and subsequently
induces apoptosis within cancer cells.
Administration rate has varied from a 15-120 min infusion, 1
mg/min infusion, 6-8 hr infusion, 24 hr infusion, or per protocol
Cancer of cervix, endometrium, prostate, esophagus,
kidney; non-small cell lung cancer; head & neck
squamous cell cancer; osteogenic sarcomas; bone
marrow transplants BSA(body surface area) for men
75-100 mg/m² IV q4Weeks when used with of 1.91 square meter M2 and
cyclophosphamide   1.71M2 for women.
Oncology center of UK
100 mg/m² IV q4Weeks as single agent - 12 -
 Altretamine
HEXALEN® (altretamine) capsules may be administered either for 14
or 21 consecutive days in a 28 day cycle at a dose of 260 mg/m²/day.
The total daily dose should be given as 4 divided oral doses after meals
and at bedtime. There is no pharmacokinetic information supporting
this dosing regimen and the effect of food on HEXALEN®
(altretamine) capsules bioavailability or pharmacokinetics has not been
evaluated.

Side effects: nausea and vomiting, Peripheral neuropathy

and central nervous system symptoms (mood disorders,
disorders of consciousness, ataxia, dizziness, vertigo).
Leukopenia, Thrombocytopenia

 BSA(body surface area) for men of 1.91 M and 1.71M for women. Oncology center of UK
2 2
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Nitrosoureas are a group of alkylating agents
that have a special action. The other alkylating
agents listed above cannot travel into the brain,
but nitrosoureas are able to do so. They can enter Carmustine
the brain because they are able to cross through
the area known as the blood-brain barrier, a
special area that keeps most drugs out of the
brain. This action makes these drugs useful in
treating certain types of brain tumors. Lomustine

• Carmustine
• Lomustine
• Streptozocin
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INDICATIONS
BiCNU® (carmustine for injection) is indicated as palliative
therapy as a single agent or in established combination
therapy in the following:
• Brain tumors glioblastoma, brainstem glioma,
medulloblastoma, astrocytoma, ependymoma, and
metastatic brain tumors.
• Multiple myeloma in combination with prednisone.
• Relapsed or refractory Hodgkin's lymphoma in
combination with other approved drugs.
• Relapsed or refractory Non-Hodgkin's lymphomas in
Common side effects of BiCNU include:
combination with other approved drugs.
• nausea,
The recommended dose of BiCNU as a single agent in • vomiting,
previously untreated patients is 150 to 200 mg/m² • headache,
intravenously every 6 weeks. Administer as a single dose • flushing,
or divided into daily injections such as 75 to 100 mg/m² • injection site reactions (pain, swelling, redness, or
on two successive days. Lower the dose when BiCNU is
darkened skin color).
used with other myelosuppressive drugs or in patients in
whom bone marrow reserve is depleted. Administer
BiCNU for the duration according to the established
regimen. Premedicate each dose with anti-emetics. - 15 -
 Antimetabolites
Antimetabolites interfere with DNA and RNA by
acting as a substitute for the normal building blocks of
RNA and DNA. When this happens, the DNA cannot
make copies of itself, and a cell cannot reproduce.
They are commonly used to treat leukemias, cancers of
the breast, ovary, and the intestinal tract, as well as
other types of cancer.

• Azacitidine • Clofarabine
• 5-fluorouracil (5-FU) • Cytarabine (Ara-C)
• 6-mercaptopurine (6-MP) • Decitabine
• Capecitabine (Xeloda) • Floxuridine
• Cladribine • Fludarabine

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 • Generic Name: azacitidine
• Brand Name: Vidaza
VIDAZA® is indicated for treatment of patients with the
following French-American-British (FAB)
myelodysplastic syndrome subtypes: refractory anemia
(RA) or refractory anemia with ringed sideroblasts (if
accompanied by neutropenia or thrombocytopenia or Common side effects may include:
requiring transfusions), refractory anemia with excess  fever, chills, bruising, or other signs of low blood cell
blasts (RAEB), refractory anemia with excess blasts in counts;
transformation (RAEB-T), and chronic myelomonocytic  lung infection;
leukemia (CMMoL).
 low potassium;
The recommended starting dose for the first treatment
cycle, for all patients regardless of baseline hematology  nausea, vomiting, stomach pain, loss of appetite;
laboratory values, is 75 mg/m2 subcutaneously or  constipation, diarrhea;
intravenously, daily for 7 days.
Repeat cycles every 4 weeks. The dose may be increased  joint pain, pain in your arms or legs;
to 100 mg/m2 if no beneficial effect is seen after 2  feeling weak or tired;
treatment cycles and if no toxicity other than nausea and
 dizziness; or
vomiting has occurred. It is recommended that patients
be treated for a minimum of 4 to 6 cycles. - 17 -  redness where an injection was given.
 Anthracyclines
Anthracyclines is a class of drugs used in
cancer chemotherapy that are extracted from
Streptomyces bacterium. These compounds are
used to treat many cancers, including
leukemias, lymphomas, breast, stomach,
uterine, ovarian, bladder cancer, and lung Anthracycline chemotherapy medicines are:
cancers. The first anthracycline discovered was Adriamycin (chemical name: doxorubicin)
daunorubicin (trade name Daunomycin), which Ellence (chemical name: epirubicin)
is produced naturally by Streptomyces Doxil (chemical name: doxorubicin)
peucetius, a species of actinobacteria. Clinically daunorubicin (brand names: Cerubidine,
the most important anthracyclines are DaunoXome)
doxorubicin, daunorubicin, epirubicin and mitoxantrone (brand name: Novantrone)
idarubicin

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 Anthimicrotubula agents Protoplasmic Cytoskeleton Elements

Highly dynamic mitotic-spindle microtubules are among the

most successful targets for anticancer therapy. Microtubule-
targeted drugs, including paclitaxel and Vinca alkaloids, were
previously considered to work primarily by increasing or
decreasing the cellular microtubule mass. Although these
effects might have a role in their chemotherapeutic actions, at
lower concentrations, microtubule-targeted drugs can suppress
microtubule dynamics without changing microtubule mass; this
action leads to mitotic block and apoptosis. In addition to the
expanding array of chemically diverse antimitotic agents, some
microtubule-targeted drugs can act as vascular-targeting agents,
rapidly depolymerizing microtubules of newly formed
vasculature to shut down the blood supply to tumors.

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 Taxanes are a class of diterpenes. They were originally identified from plants of the
genus Taxus (yews), and feature a taxadiene core.
Mechanism of Action
Taxanes reduce the critical concentration of tubulin
required for microtubule assembly, resulting in a
mitotic block at the metaphase/anaphase junction
and in cell cycle phase–specific activity. In addition
to cytotoxic activity, ant angiogenesis is
another mechanism of antitumor activity.

Paclitaxel (Taxol) and docetaxel

(Taxotere) are widely used as
chemotherapy agents.

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 Paclitaxel is an antineoplastic agent which acts by Common side effects of paclitaxel include:
inhibitor of cellular mitosis and which currently
Hair loss
plays a central role in the therapy of ovarian,
Anemia
breast, and lung cancer. Therapy with paclitaxel
Joint pain
has been associated with a low rate of serum
Muscle pain
enzyme elevations, but has not been clearly linked
Diarrhea
to cases of clinically apparent acute liver injury.
Nausea/vomiting
• Previously untreated: 175
mg/m2 intravenously (IV) over 3 hours every Numbness and tingling in extremities
3 weeks (follow with cisplatin), OR Low blood platelet count (thrombocytopenia)
• 135 mg/m2 IV over 24 hours every 3 weeks
(follow with cisplatin)
• Previously treated: Various regimens exist:
135-175 mg/m² IV over 3 hours every 3
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 Topoisomerase inhibitors Topoisomerase I inhibitors are mainly used in
DNA topoisomerases are enzymes that regulate the treatment of colorectal and ovarian cancers.
DNA topology and are essential for the integrity
of the genetic material during transcription,
replication and recombination processes.
Inhibitors of the mammalian enzymes are
widely used antitumor drugs. They stabilize
topoisomerase-DNA cleavable complexes by
hindering the DNA relegating step of the
catalytic reaction, thus resulting in DNA
cleavage stimulation. Divided into Top1,Top2a
and Top2b • Etoposide.
• Irinotecan.
• Teniposide.
• Topotecan.

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 Irinotecan Brand Names: US Camptosar
injectable solution 100mg/mL
• Regimen 1 (Weekly): 125 mg/m² IV infusion over
90 minutes on days 1, 8, 15, 22, then 2 weeks off,
then repeat  
• Regimen 2 (Once Every 3 Weeks): 350
mg/sq.meter IV infusion over 30-90 minutes
q3Weeks

• Hair loss.
Common side effects:
• Constipation, stomach pain, upset stomach,
throwing up, or feeling less hungry.
• Feeling dizzy, sleepy, tired, or weak. • Mouth irritation or mouth sores.
• Trouble sleeping. • Back pain.
• Headache. • Sweating a lot.
• Weight loss.
• Gas.- 23 -
Other types of drugs used to treat cancer
Other drugs and biological treatments are used to treat cancer, but aren’t considered
chemotherapy. They often have different side effects than chemotherapy. Many are
used along with surgery, chemo, or radiation therapy.
Targeted therapies
Targeted therapies work by finding specific substances called proteins or receptors
that some cancer cells have. The protein or receptor is precisely targeted by the
drug, so normal cells are not affected by the drugs. This is different than how
traditional chemotherapy drugs work. Targeted drugs can be used as the main
treatment for a cancer, or they may be used after treatment to keep the cancer under
control or keep it from coming back.

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 Hormone therapy
Drugs in this category work on different actions of hormones that
make some cancers grow. These drugs are used to slow the growth
of certain breast, prostate, and endometrial (uterine) cancers,
which normally grow in response to natural sex hormones in the
body. They work by making the cancer cells unable to use the
hormone they need to grow, or by preventing the body from
making the hormone.

Immunotherapy
Immunotherapy is a type of treatment that uses drugs to boost or alter a
person's immune system. These drugs are used with certain types of cancer
to help a patient's immune system recognize and attack cancer cells.

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 Thank you for your attention !

Abdullaev Dzhumadil, pharmD

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International Medical University