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Chemotherapy: Eunice Joy B. Guillergan, RN Staff Nurse St. Paul's Hospital Iloilo
Chemotherapy: Eunice Joy B. Guillergan, RN Staff Nurse St. Paul's Hospital Iloilo
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A. Definition of Terms
Chemotherapy
Modality of treatment for both cancerous & non-
cancerous conditions
Neoplasm
Tumor, any new & abnormal growth especially
one in which cell multiplication is uncontrolled &
progressive
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Goals of Chemotherapy
Curative Chemotherapy
Aimed @ the total elimination of the cancer cells
including those that may have spread to other parts of the body.
Adjuvant Chemotherapy
Is used in addition to surgery & or radiation. Used to
eliminate systemic microscopic cancerous cells and provide a
complete cure or a remission.
Palliative Chemotherapy
Aims to reduce tumor size, extend life, & improve
over-all-quality of life.
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B. Log-kill Hypothesis
Chemotherapy kills a constant proportion of the
remaining cancer cells with each dose.
Between doses, cell regrowth occus. When therapy is
successful, cell killing is greater than cell growth.
Chemotherapy
Cancer Treatments
Cells
10 10
1 log cell regrowth
10 8
3 log cell kill
10 6
10 4
10 2
Time
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C. Cell Cycle Theory
Developed to target cells at the cellular development
lever
Developed to hit cell cycle phases & cannot detect the
difference between normal & malignant cell
Works best on rapidly dividing cells such as those in hair,
skin, mucous membranes, & the bone marrow system.
(These systems are the most likely to have effects related
to chemotherapy administration e.g., baldness)
Classified as:
1. Cell Cycle Phase-Specific
The agents work to kill cells only in a specific part of
the cell cycle.
2. Cell Cycle Phase-Non-specific
The agents do not depend on the phase of the cycle to
be active, but affect cells @ all phases.
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Cell Cycle
A sequence of steps by which normal & malignant cells
reproduce.
1. G0 Phase
• Resting phase
• Cells in this phase are not within the active cell cycle
• Cells do not undergo replication
• Cells can stay in this phase @ varying lengths of time &
divert back into the G1 phase based on the organism’s
needs.
2. G1 Phase
• Is called the first gap or first growth phase of the cellular
cycle
• In this phase, the cell prepares for DNA synthesis by
producing RNA & protein.
• Also includes a resting phase called G0.
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Cell Cycle
3. Synthesis Phase
• Where DNA is synthesized
• DNA holds the genetic information needed for growth,
repair & replication of the cell.
• Normal & malignant cells differ in the amount of time
they spend in the S phase
• Various chemotherapeutic agents are aimed @
impacting the cell in this phase, thereby disrupting DNA
organization & synthesis, resulting in cell death.
4. G2 Phase
• The 2nd growth phase or second gap
• Synthesis of RNA & protein occurs as the cell prepares
for mitosis
• The cell produces mitotic spindle apparatus during this
phase where chromosomes are condensed and prepared
for the process of division.
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Cell Cycle
5. M Phase
• Mitosis
• Where cell division actually occurs
• The M phase may either re-enter the cell cycle @ G1 or
go into G0 to rest & wait for activation
• Mitosis has 4 steps:
o P – Prophase
o M – Metaphase
o A – Anaphase
o T - Telophse
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C. Classification of Cytotoxic Agents
& Biologic Response Modifiers
1. ALKALATING AGENTS
A. Nitrogen mustards
• Produced highly reactive carbonium ion compounds
that react with the electron-rich areas of susceptible
molecules.
• E.g. Cyclophosphamide Estramustine
Chlorambucil Melphalan
Ifosfamide Mechlorethamine
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TYPES OF ALKYLATING AGENTS
B. Ethylenamine Derivatives
• E.g. Triethylenethiophosphoramide (Thiotepa)
C. Alkyl Sulfonates
• Busulfan is the only clinically active compund in the
group
• It appears to interact more with cellular -thiol groups
than with nucleic acids.
D. Triazenes
• E.g. Dacarbazine
E. Nitrouureas
• Undergo rapid, spontaneous activation in acqueous
solution to form products capable of alkylation and
carbamoylation.
• E.g. Carmustine
Lomustine
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TYPES OF ALKYLATING AGENTS
F. Metal Salts
• Inhibit DNA synthesis through the formation of
intrastrand cross-links in DNA
• E.g. Cisplatin
Carboplatin
2. ANTIMETABOLITES
• Cell-Cycle Specific
• Group of low molecular weight compounds that exert
their effect by virtue of their structural/functional
similarity to naturally occurring metabolites involved in
nuclear acid synthesis.
TYPES OF ANTIMETABOLITES
A. Folic Acid Analogs
• Inhibit the enzyme dihydrofolate reductace
• E.g. Methotrexate
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TYPES OF ANTIMETABOLITES
B. Pyramidine Analogs
• Inhibit critical enzymes necessary for nucleic acid
synthesis and may become incorporated into DNA &
RNA
• E.g. Fluoracil
Cytarabine
Capecitabine
Gemcitabine
C. Purine Analogs
• They interfere with normal purine interconversions and
thus with DNA & RNA synthesis.
• E.g. Mercaptopurine
Thioguanine
Fludarabine
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3. NATURAL PRODUCTS
• Grouped together not on the basis of activity but
because they are derived from natural sources such as:
o Plant products
o Fermentation products (species of the soil fungus
Streptomyces)
o Bacterial products
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TYPES OF NATURAL PRODUCTS
B. Podophylline Derivatives
• Derived from May apple plant
• Forms Topoisomerase II
• Topoisomerase I Inhibitor (Irinotecan)
• E.g. Etoposide
Teniposide (semi-synthetic
podophyllotoxinx)
C. Antibiotics
• Group of related antimicrobial compounds produced by
Streptomyces species in culture
• E.g. Dactinomycin
Anthracyclines : Doxorubicin
( Vesicant ) Daunorubicin
Epirubicin
Idarubicin
Anthracenedione
Mitoxantrone
o Topoisomerase II dependent DNA cleavage &
intercalate with DNA double helix.
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TYPES OF NATURAL PRODUCTS
D. Taxanes
• Microtubule polymer stabilizer
• E.g. Paclitaxel
Docetaxel
B. Anti-androgen
• Inhibits nuclear androgen binding
• E.g. Bicalutamide & Flutamide
C. Corticosteroids
• Cause lysis of lymphoid tumors that are rich in specific
cytoplasmic receptors
• E.g. Dexamethasone & Prednisone
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TYPES OF HORMONES & HORMONE ANTAGONISTS
D. Estrogens
• Suppress testosterone production in males and alter
breast cancer cell response to prolactin.
• E.g. Diethylsylbestrol
E. Progestin
• Appears directly at the level of malignant cell receptor to
promote differentiation.
• E.g. Megestrol acetate
Medroxyprogesterone acetate
F. Estrogen Antagonist
• Competes with estrogen for binding on the cytosol
estrogen receptor protein in cancer cells
• E.g. Tamoxifen
G. Aromatase Inhibitor
• Non-steroidal inhibitor
• Anioglutethimide (non-selective) having many
biochemical sites of inhibition of steroids genesis.
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TYPES OF HORMONES & HORMONE ANTAGONISTS
G. Aromatase Inhibitor
• Anastrazole, Letrozole (selective) primarily blocks the
conversion of adrenally-generated androstenedione to
estrone by aromatase in peripheral tissues without
inhibition of progesterone or corticosteroids synthesis.
I. Thyroid Hormones
• Inhibit the release of thyroid-stimulating hormone
(TSH), thus inhibiting the growth of well-differentiated
thyroid tumors.
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5. MISCELLANEOUS AGENTS
• Biphosphonates (Pamidronate)
• Uroprotector (Uromitexan)
• Cytoprotector (Amifostine)
6. BIOLOGIC AGENTS
• Genetically engineered versions of naturally occurring
proteins or therapeutic molecules based on proteins.
1. Erythropoietin
• Promotes the proliferation and differentiation of
committed erythoid precursors
• Results in decreased transfusion requirements during
chemotherapy
• E.g. Epoetin alfa/beta
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HEMATOPOEITIC GROWTH FACTOR & MONOCLONAL
ANTIBODIES IN CANCER THERAPY
3. Monoclonal Antibodies
• Are antibodies that bind to tumor-associated cell
surfaces antigens thereby destroying tumor cells through
a number of possible mechanisms, including activation
of complement & antibody-dependent cell-mediated
cytotoxicity.
• Indicatedfor breast carcinoma that has over expression
of Her2/neu (c-erb8-2).
• E.g. Trastuzumab
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