Download Cancer and Chemotherapy

Cancer and Chemotherapy
Cancer
• Although there are many kinds of cancer, they
all start because of out of control growth of
abnormal cells
• Normal body cells grow, divide, and die in an
orderly fashion
Cancer
• Because cancer cells continue to grow and
divide, they are different from normal cells
• Instead of dying, they outlive normal cells and
continue to form new abnormal cells
Rapid uncontrolled growth
• Compresses on surrounding anatomy
• Abnormal hormone synthesis
• Rapid growth exceeds vascular ability to
supply the tumor resulting in necrosis
• Cachexia, malnutrition
Cancer
• Cancer cells develop because of damage to
DNA, and it’s regulatory mechanisms
• When DNA becomes damaged, the body is
usually able to repair it
Cancer
• In cancer cells however, damaged DNA is not
repaired
• People can inherit damaged DNA, which
results in approximately 10 percent of all
cancer
Cancer
• More often, though, a person’s DNA becomes
damaged by exposure to something in the
environment or random cellular events
Known causes of cancer
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Environmental
- ultraviolet rays
- drugs
- asbestos and other occupational hazards
- alcohol
- smoking
Causes of cancer
• Viruses
• - HTLV-1 causative agent for T cell leukemia
• - oncogenic viruses
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- may code for growth factors and may
amplify them, may control cell death
suppressor gene or tumor suppressor genes
Body defenses
• The body is able to launch an immune
cytotoxic response to tumors
• Once the tumor load has exceeded this
system, the tumor grows out of control
Cancer
• Most cancers originate almost anywhere in
the body and usually form as a solid tumor
Cancer
• Others such as leukemia and myeloma, are
sometimes referred to as liquid tumors
• These cancer cells involve the blood and
blood-forming organs (bone marrow) and
circulate through other tissues, where they
grow
Carcinoma
• Carcinomas: the most common type of cancer,
these tumors arise from the cells that cover
external and internal body surfaces
• The most frequent cancers of this type in the
US are lung, breast, colon and prostate cancer
Sarcoma
• Sarcomas: cancers that arise from cells found
in the supporting tissues of the body, such as
bone, cartilage, fat, connective tissue, and
muscle
Lymphoma
• Cancers that arise in the lymph nodes and
tissues of the body’s immune system
Leukemia
• Leukemias: cancers of the immature blood
cells that grow in the bone marrow and tend
to accumulate in large numbers in the
bloodstream
Primary
• The place where a cancer starts is called the
primary site
Metastasis
• From the primary site, it can spread
(mestastasize) to other parts of the body
• The cancer that has spread to other parts of
the body are called metastasis or metastases
Primary is name
• Regardless of where a cancer may spread, it is
always named for the place it began
• For instance, breast cancer that spreads to the
liver is still called breast cancer not liver
cancer
Different Cancers
Different Treatments
• Different types of cancer can behave very
differently. For example, lung cancer and
breast cancer are very different diseases. They
grow at different rates and respond to
different treatments. That is why people with
cancer need treatment that is aimed at their
particular kind of cancer
Malignant is cancerous
Benign is noncancerous
• Not all tumors are malignant (cancerous)
• Benign, or noncancerous, tumors do not
spread to other parts of the body and, with
very rare exceptions, are not life-threatening
Biopsy
• A biopsy is taking a surgical sample of the
suspicious tissue
• This is done by a large hollow needle or
excision (surgical removal)
Margins
• When a tumor is excised surgically, it is sent to
the pathologist for examination and diagnosis
• The pathologist can tell us if the biopsy is
surrounded by normal tissue, or if the biopsy
cut through the tumor, meaning part of the
tumor has been left in the patient
Biopsy Margin
Biopsy Margin
• Positive margins means that part of the tumor
has been left behind
• This is not an unusual situation it is not always
possible to remove the entire tumor at biopsy
Pathologist
• In addition to margins, the pathologist tells us
many things about the tumor that we need to
know
• Gross description (seen with unaided eye)
• Microscope description
Pathologist
• Gross description
• - size (very important) – for staging and
treatment
• - color
• - weight
Pathologist
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Microscopic description
- margins
- cellular characteristics
- histological grade
- special staining techniques
Pathologist Histologic Grade
• Histologic grade tells us how abnormal the
cancer cell is
• Low grade cells are well differentiated
• High grade cells are poorly differentiated
Pathologist Special Stains
• Pathologists are able to use special stains to
reveal characteristics of cancer
Staging
• Although the pathology report is important to
staging the cancer, there are many other
factors involved
• Different types of cancer have different
staging systems
Staging
• Staging reflects the amount and location of
cancer in the body to make sure a person gets
the proper treatment for his or her specific
treatment
Staging
• The treatment for Stage 1 breast cancer may
be surgery and radiation, while a more
advanced stage of breast cancer, stage 2 or 3
may require treatment with chemotherapy as
well
Staging
• Staging helps predict the course of cancer is
likely to take
• Staging implies prognosis
TNM staging
• Some caners of the blood such as leukemias
are not staged TNM because they are
assumed to be in all parts of the body
TNM staging
• Cancers in or around the brain are not staged
using the TNM, since these cancers can
interfere with vital functions of the brain and
body before they even begin to spread
TNM staging
• For most cancers, the stage is based on 3 main
factors:
• - T. the original (primary) tumor’s size and
whether or not the tumor has grown into
other nearby areas.
• - N. whether or not the cancer has spread to
the nearby lymph nodes
• - M. whether or not the cancer has
metastasized to distant areas of the body
TNM
• The T category describes the original (primary)
tumor and it’s size
TNM
• The numbers T1- T4 describes the tumor size
and/or level of invasion into nearby
structures. The higher the T number, the
larger the tumor and/or the further it has
grown into nearby structures
TNM
• T0 means there is no evidence of primary
tumor (the primary tumor cannot be found).
• Tx means the tumor can’t be measured or
evaluated
• Tis means the cancer is in situ (the tumor has
not started growing into the structures around
it)
TNM
• The N category describes whether or not the
cancer has reached lymph nodes
TNM
• N0 means nearby lymph nodes do not contain
cancer
• N1-N3 describe the size, location and/or the
number of lymph nodes available. The higher
the N number, the more lymph nodes are
available
• Nx means the nearby lymph nodes can’t be
measured or evaluated
TNM
• The M category tells whether there are distant
metastases (spread of cancer to other parts of
the body)
TNM
• M0 means that no distant metastases were
found
• M1 means that distant metastases were found
• Mx means mestastasis can’t be measured or
evaluated
Each primary type has it’s own systems
• Each cancer type has it’s own version of this
classification system, so letters and numbers
don’t always mean the same thing for every
kind of cancer. For example, for some cancers,
classification may have some subcategories,
such as T3a and T3b, while others may not have
an N3 category
Why is each staging different from
each other?
• Staging helps predict the course a cancer is
likely to take
• Staging implies prognosis
Cancer Chemotherapy
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Cancer chemotherapy
Basic drug subclasses
- alkylating agents
- antimetabolites
- plant alkaloids
- antibiotics
- hormones
- biologic response modifiers
Many cancer chemotherapy agents are
described by how they affect the cell
cycle
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M phase – mitosis which is cellular division
- drugs that block mitosis are:
M phase
CCS (Cell Cycle Specific)
Antimitotic
• The G1 phase is the first growth phase
• The S phase is the DNA synthesis phase
• drugs that block DNA synthesis are:
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S phase
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CCS (Cell Cycle Specific)
• The G2 phase is the second growth phase
• drugs that block the growth after DNA
synthesis are: G2 phase CCS (Cell Cycle
Specific)
• Many drugs are Cell Cycle NON Specific (CCNS)
• Meaning they are cytotoxic during the entire
cell cycle
Alkylating Agents
• The first alkylating agents were derived from
nitrogen mustards
• Nitrogen mustards were used in WWI as
chemical warfare agents (mustard gas) causing
blistering of the skin (vesicants)
Mustard gas in the battlefield
Mustard gas
Alkylating agents
• Nitrogen mustards were later found to be very
effective in treating cancer
Alkylating agents
• The alkylating agents form reactive molecular
species that alkylate nucleophilic groups on
DNA bases, particularly the N-7 position of
guanine
Alkylating agents
• Alkylating agents cross-links DNA during all
phases of the cell cycle, resulting in disruption
of DNA function, cell cycle arrest, and
apoptosis
Alkylating agents
• The alkylating agents are cell cycle nonspecific
agents that damage DNA
Alkylating agents
• Cell Cycle NON Specific
• CCNS
• Meaning they are cytotoxic during the entire
cell cycle
Alkylating agents
• Because they are vessicants, causing blistering
of the skin, these agents can be very
damaging if they are not properly
administered
Alkylating Agents
Nitrogen Mustards
• Chlorambucil
• Cyclophosphamide (Cytoxan®)
• Mecloethamine
Alkylating Agents
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Busulfan
Dacarbazine
Procarbazine
Carmustine
Lomustine
Alkylating Agents
Platinum Analogs
• Ciplastin
• Carboplastin
• Oxaplatin
Cancer Chemotherapy
Basic Drug Subclasses
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Alkylating Agents
Antimetabolites
Plant Alkaloids
Antibiotics
Hormones
Biologic Response Modifiers
Antimetabolites
• Antimetabolites interfere with DNA and RNA
production
• Antimetabolites
• S phase
• Cell Cycle Specific
• CCS
• Meaning they interfere with the S phase
Antimetabolites
• Methotrexate (meh-thuh-TREK-sayt) (MTX)
• Folic acid antagonist that binds to
dihydrofolate reductase
• Interferes with DNA and RNA synthesis by
preventing nucleoside production
Antimetabolites
• Purine antagonists
• - mercaptopurine (mer-CAP-to-pur-een) (6MP)
• - Thioguanine (thio-GWA-neen) (6-TG)
• Interferes with DNA and RNA synthesis by
preventing nucleotide production
Fluoropyrimidine
Antimetabolites
• Pyrimidine antagonists
• - stops DNA and RNA synthesis by preventing
nucleoside production
• Fluorouracil (floor-oh-YOOR-ul-sil) (5-FW)
• Capecitabine (ka-peh-SITE-uh-been) (Xeloda®)
• - 5-FU prodrug
Plant Alkaloids
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Taxanes
Taxane (TAK-sayn)
The taxanes are produced by Yew trees
Taxanes interfere with microtubules and are
mitotic inhibitors
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Taxane Alkaloids
M phase
Cell Cycle Specific
CCS
Meaning they interfere with mitosis
• Yew Trees Produce Taxanes
Taxanes
• Paclitaxel (PA-klih-TAK-sil) (Taxol®)
• Docetaxel (doh-she-TAK-sil) (Taxotere®)
Vinca Alkaloids
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M phase
Cell Cycle Specific
CCS
Meaning they interfere with mitosis
• Periwinkles produce Vinca Alkaloids
Taxanes
• Taxanes
• - Paclitaxel (PA-klih-TAK-sil) (Taxol®)
• - Docetaxel (doh-she-TAK-sil) (Taxotere®)
Vinca Alkaloids
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Vinblastine (vin-BLAS-teen)
Vincristine (vin-KRIS-teen)
- from Vinca rosea, periwinkle plant)
- binds to tubulin and causes mitosis to stop
Vinca Alkaloids
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M phase
Cell Cycle Specific
CCS
Meaning they interfere with mitosis
• Periwinkles produce Vinca Alkaloids
Plant Alkaloids
Captothecins
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Camptothecin (KAMP-toh-THEK-in)
- from Camptotheca acuminate tree)
Topotecan (toh-poh-TEE-kan)
Irinotecan (I-rih-noh-TEE-kan)
Captothecins are Topoisomerase
Inhibitors
• Topoisomerase (TOH-poh-i-SAH-meh-rays)
• Topoisomerase is an enzyme required for DNA
reproduction.
• Inhibiting topoisomerase interferes with DNA
replication
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Comptothecins are:
S phase
Cell Cycle Specific
CCS
Meaning they interfere with DNA synthesis
• Camptotheca Acuminata Trees or happy tree
produce camptothecins
Plant Alkaloid Topoisomerase
Inhibitors
• Epipodophyllotoxin (EH-pih-POH-doh-FIH-lohTOK-sin)
• Epipodohphyllotoxin is extracted from the
mandrake root of the Podophyllym peltatum.
It is a type of topoisomerase inhibitor
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Podophyllotoxins
S phase
Cell Cycle Specific
CCS
Meaning they interfere with DNA synthesis
• Podophyllum peltatum
• “Mayapple” produces epipodophyllotoxin
Antibiotics
• Anthracyclines (AN-thruh-SY-klin)
• A type of antibiotic that comes from
Streptomyces bacteria. Anthracyclines are
used to treat many types of cancer.
Anthracyclines not only block DNA synthesis,
they damage DNA during all phases of the cell
cycle. They are too toxic to use for bacterial
infections.
Anthracyclines
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Daunorubicin
Doxorubicin (Adriamycin®)
Epirubicin (Ellence®)
Idarubicin
Mitoxantrone (analog)
• Anthracyclines are Cell Cycle NON Specific
• CCNS
• Meaning they are cytotoxic during the entire
cell cycle
Bleomycin
• Bleomycin is a glycopeptide antibiotic
produced by the bacterium Streptomyces
verticillus
• Bleomycin not only interferes with DNA
synthesis and damages DNA and is especially
active during the G2 phase
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Bleomycins
G2 phase
CCS
Meaning they interfere with DNA synthesis
mostly during S and G2
Hormones
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Glucocorticoids – Prednisone
Gonadal Hormone Antagonists
- Estrogen Antagonist
- Androgen Antagonists
Gonadotropin Releasing Hormone Analogs
Aromatase Inhibitors
Glucocorticoids
• Prednisone is a glucocorticoid commonly used
in combination with other agents in the
treatment of leukemias and lymphomas
Estrogen Antagonist
• Tamoxifen Nolvadex ® is an estrogen receptor
modulator commonly used to treat breast
cancer
Androgen Antagonist
• Flutamide, Eulixin® is an androgen antagonist
commonly used to treat prostate carcinoma
GnRH analogs
• Leoprolide, Lupron®
• Goserelin, Zoladex®
• GnRH analogs commonly used to treat
prostate carcinoma
Aromatase Inhibitors
• Aromatase is an enzyme important in
estrogen formation
• Aromatase inhibitors are used to treat breast
carcinomas
Aromatase Inhibitors
• Anastrozole, Arimidex® (ANAS)
• Letrozole, Femara® (LTZ)
Biologic Response Modifiers
Interferons
• Interferons are naturally occuring endogenous
glycoproteins with antiviral and antineoplastic
activity
• Interferon A is effective against certain
leukemias and lymphomas
Biologic Response Modifiers
Monoclonal Antibodies
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Alemtuzumab Campath®
Bevacizumab Avastin®
Gemtuzumab Mylotarg®
Ibritumomab Zevalin®
Rituximab Rituxan ®
Tositumomab Bexxar ®
Trastuzumab Herceptin®
Biologic Response Modifiers
Monoclonal Antibodies
• Trastuzumab (tras-TOO-zuh-mab) Herceptin®
• A monoclonal antibody that binds to HER2
(human epidermal growth factor receptor 2)
and can kill HER2 – positive cancer cells
• Trastuzumab (Herceptin) is used to treat
breast cancer that HER2 – postive and has
spread after treatment with other drugs
Biologic Response Modifiers
Monoclonal Antibodies
• Bevacizumab (beh-vuh-SIH-zoo-mab)
Avastatin®
• Bevacizumab (Avastatin) binds to vascular
endothelial growth factor (VEGF) preventing
angiogenesis (the growth of new blood vessels
that tumors need to grow).
Biologic Response Modifiers
Tyrosine Kinase Inhibitors
• Imantinib Gleevic® inhibits the tyrosine kinase
activity of the protein product of the Bcr-Abl
gene commonly expressed in Chronic
Myelogenous Leukemia
Biologic Response Modifiers
Tyrosine Kinase Inhibitors
• Gefitinib, Iressa®
• Erlotinib, Tarceva®
• Inhibits the tyrosine kinase activity of the
epidermal growth factor required for
angiogenesis
Adjuvant Chemotherapy
• Systemic therapy given to patients with no
evidence of cancer after surgery is called
adjuvant therapy
• While surgery is used to remove all of the
cancer that can be seen, adjuvant therapy is
used to kill any cancer cells that may have
been left behind that can’t be seen
Neoadjuvant Chemotherapy
• Chemotherapy given before surgey is called
neoadjuvant therapy
• Neoadjuvants can shrink tumors and reveal
responsiveness to tumors before surgery
allowing for less aggressive therapy
Rescue therapy
• Rescue therapy is any agent that prevents or
lessens the toxicity of cancer
chemotherapeutic agents
• National Cancer Institute / cancer.org
• American Cancer Society Cancer.org