Transcript CHEMOTHERAPY

CHEMOTHERAPY
Dr.M.Torfehnezhad
Pediatrician
Definition:
Chemotherapy
• The treatment of cancer using specific
chemical agents or drugs that are
destructive to malignant cells and tissues.
The term comes from two words that mean
"chemical" and "treatment."
Cytotoxic
• literally translated means ‘toxic to cells’.
The Cell Cycle
The Cell Cycle
Mitosis
Cell Biology: Mitosis

A cell in mitosis
Normal Cell Characteristics:
Metabolism. Strictly controlled &
predictable
 Maturation & Specialisation. Occurrs
before dividing. Strictly controlled.
 Reproduction = Cell death
 Contact Inhibition. Mechanism for
switching off division when in contact
with different cells
 Recognition. Like cells stay together.

Cancer Cell Characteristics:
Unchecked & Uncontrolled Growth
 Loss of contact inhibition
 Loss of capacity to differentiate
 Increased growth fraction
 Chromosomal Instability
 Capacity to metastasise
 Altered biochemical properties

Chemotherapy and Cancer Cells
Cell Cycle specific :
Most active against cells in a specific
phase therefore need prolonged exposure
or repeated doses.
Cell Cycle Non-specific:
Most effective against actively dividing
cells
Chemotherapy
Chemotherapy may be used
conventionally to:
 Cure patients
 Prolong survival
 Palliative care symptom control
Chemotherapy
Combination Therapy.
Prevents resistance.
Adjuvant Therapy.
Administered after primary therapy
e.g.Surgery
Neo adjuvant Therapy:
Given before surgery to reduce
tumour size.
Chemotherapy
Over 50 different chemotherapy drugs
Administered as an outpatient or inpatient
depending on toxicity
Modes of administration include:
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Oral e.g. Methotrexate, Hydroxyurea
IV: Canula/Indwelling Central Venous Catheter
Sub cut
Intracavity e.g pelvic cavity, bladder
Intrathecal. Can be fatal if wrong drug
administered!
Intrathecal Chemotherapy
Drugs Used in Cancer
Chemotherapy

Cytotoxic Agents
Alkylating Agents
 Antimetabolites
 Cytotoxic antibiotics
 Plant derivatives
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Hormones
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Suppress nat’l hormone secr’n or
antagonize hormone action
Misc (mostly target oncogene products)
Rand 50.3
Alkylating Agents
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Contain chemical groups that bind cell
nucleophiles
Alkylating Agents
Cisplatin (Platinol), Mechlorethamine
(Mustargen) and Cytoxan are commonly
used agents in this category
 Carboplatin- more myelotoxic
 Action: substitutes an alkyl chemical
structure for a hydrogen atom in the DNA
 This results in a cross-linking of each
strand of DNA, thus preventing cell
division
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Alkylating Agents, con’t
Effective against lymphomas, leukemias,
myelomas, ovarian, testicular, breast,
and pancreatic cancers
 Cause bone marrow suppression,
alteration in mucous membranes, severe
N&V, alopecia
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Alkylating Agents, con’t
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Can also cause ototoxicity and
nephrotoxicity. Be sure the patient is
well hydrated before receiving these
agents
Cyclophosphamide
Most common
 Prodrug – liver metab by CYP P450
MFO’s
 Effects lymphocytes
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Also immunosuppressant
Oral or IV usually
 SE’s: n/v, bone marrow dpression,
 Cytoxan can cause hemorrhagic cystitis
(give MESNA to protect the bladder)
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Antimetabolites
These drugs have a structure similar to a
necessary building block for the
formation of DNA.
 These drugs are accepted by the cell as
the necessary ingredient for cell growth,
but because it is an imposter, it interferes
with the production of DNA.
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Antimetabolites
Kill cells in S phase
 Three main groups
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Folate antagonists
 Pyr analogs
 Pur analogs
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Folic Acid Analogs
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Folic acid essential for synth purines, and
thymidylate
Methotrexate
Higher affinity for enz than does FH2
  Inhib’n DNA synth
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Pyrimidine Analogs
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5-Fluorouracil
Competitive inhibitor for thymidylate
synthetase active site
 Decr’d DNA synthesis
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Gemcitabine
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Inhib’s ribonucleotide reductase  decr’d
nucleotide synth
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Cytosine arabinoside (cytarabine)
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Inhibits DNA polymerase
Gemcitabine – araC analog
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Fewer SE’s
Purine Analogs
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6-Mercaptopurine, 6-Thioguanine
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Inhibit enz’s necessary for purine synth
Fludarabine
Converted to triphosphate
 Mech action sim to ara-C
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Pentostatin
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Inhibits adenosine deaminase
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Catalyzes adenosine  inosine
Interferes w/ purinemetab, cell prolif’n
Antibiotic Antineoplastic Agents
These agents actually bind DNA, thus
inhibiting DNA and RNA synthesis and
therefore inhibiting cell growth.
 Sadly, these drugs have great potential
to cause irreversible cardiomyopathies.
 Doxorubicin (Adriamycin) is used for
acute leukemias, soft tissue/bone
cancers, lymphomas, and breast cancer
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Antibiotic Agents, con’t
Adriamycin is also a potent vessicant
(will cause tissue necrosis if it infiltrates)
 Most dangerous side effect is decreased
ejection fraction (normal is 70%). Must
do baseline CV assessment prior to
beginning Adriamycin (EKG, echo,
angiography).
 Must reduce the dose of chemo at the
first sign of heart failure
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Antibiotic agents, con’t
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Other side effects include stomatitis,
alopecia, bone marrow suppression,
hepatic impairment.
Antibiotic agents, con’t
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Dactinomycin
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Interferes w/ RNA polymerase movement  decr’d
transcr’n
Bleomycin
Glycopeptide
 Chelates Fe, which interacts w/ O2
  Gen’n superoxide and/or hydroxyl radicals
 Radicals degrade DNA  fragmentation, release of
free bases
 Most effective in G2, also active against cells in G0
 Little myelosuppression BUT pulmonary fibrosis
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Mitotic Inhibitors
These drugs are also called VincaAlkaloids
 Work by inhibiting mitosis during cell
division
 Vinblastine (Velban) and Vincristine
(Oncovin) are commonly used agents for
ALL, lymphomas, rhabdomyosarcoma)
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Mitotic Inhibitors, con’t
Neurotoxicity is a specific side effect for
this classification of drugs. Peripheral
neuropathy, alteration in bowel and
bladder tone (including paralytic ileus),
headache, tingling of fingers/hands/toes,
ataxia.
 Constipation is common due to effects
on the autonomic nervous system
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Vinca Alkaloids
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Etoposide, teniposide
From mandrake root
 Inhibit mitoch function, nucleoside
transport, topoisomerase II
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Campothecins: irinotecan, topotecan
Irinotecan requires hydrolysis  active
form
 Bind, inhibit topoisomerase II
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Hormonal Agents
Used to treat neoplasms that are
sensitive to hormonal growth controls of
the body.
 They interfere with growth-stimulating
receptors on target tissues.
 Corticosteroids are considered hormonal
agents. They retard lymphocytic
proliferation, so they help with
lymphocytic leukemias and lymphomas.
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Hormonal Agents, con’t
Corticosteroids also decrease edema
associated with tumor growth, especially
in or around the brain, spinal cord, and
mediastinum. Will decrease cerebral
edema.
 Androgens (testosterone) may be used
to treat advanced breast cancer
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Hormonal Agents, con’t
Anti-Estrogen drugs (Tamoxifen) block
the uptake of estrogen and therefore are
good for tumors that contain high
concentrations of estrogen receptors
 Estrogen may be used to treat androgensensitive cancers, such as prostate
cancer
 Progestins (Depo-Provera and Megace)
are used to treat endometrial cancer
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Chemotherapy Side Effects
Chemotherapy targets cells which are
dividing rapidly.
 Chemotherapy cannot distinguish
between normal cells and cancer cells
 Healthy Cells which have a high rate of
growth and multiplication include cells of
the bone marrow, hair, GI mucosa and
skin.
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Side effects greatest in other rapidlydividing cells
Bone marrow toxicity
 Impaired wound healing
 Hair follicle damage
 Gi epith damage
 Growth in children
 Gametes
 Fetus
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May themselves be carcinogenic
Chemotherapy Side effects contd…
Side effects may be drug specific e.g.
anthracyclines and cardiotoxicity, vinca
alkaloids and neuropathy/constipation,
bleomycin and pulmonary fibrosis
 Severity of side effects varies between
drugs.
 Side effects often occur 7-14 days post
treatment.
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Side Effects: Acute
Tumour Lysis Syndrome.
 A Metabolic Emergency.
 Occurrs due to rapid cell lysis (death) &
large amounts of cell metabolites in
blood.
 If untreated can lead to acute renal
failure, cardiac arrest and death.
Side Effects: Acute
Neutropenic Sepsis:
Occurs due to Bone Marrow Failure and
poor immune response to infection.
Predisposing factors include:
Neutropenia
Underlying disease
Chemotherapy
Venous access devices
Neutropenic Sepsis
Severe overwhelming infection where
inadequate blood flow to the tissues
results in cellular dysfunction and, if not
reversed, eventual organ failure.
 Most common micro organism is gram
negative
 Mortality rate 40-90%
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Side Effects: Acute
Haemorrhage
• Invading tumours e.g gastric MALT
lymphomas
• Haemorrhagic Cystitis related to high
dose Cyclophosphomide
Anaphylactic Reaction
Side Effects:Bone Marrow
Neutropenia:
Increased risk of infection.
Anaemia:
Tiredness, lethargy & breathlessness
Thrombocytopenia:
Increased risk of bleeding
Side Effects: Gastro-Intestinal
Nausea & Vomiting
 Diarrhoea & constipation
 Loss of appetite
 Taste Changes
 Mucositis
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Side Effects
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Example of Grade 4 Mucositis
Side Effects: Body Image
Hair Loss
 Weight Loss/ Weight Gain
 Long term central venous catheters
 Skin changes (colour, rashes, sensitivity
to sunshine, dry)
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Side Effects: Other
Fatigue: Often multi-factorial
 Peripheral neuropathy
 Altered Kidney Function
 Changes in hearing (high dose Cisplatin)
 Cardiac Toxicity (Doxorubicin/ Idarubicin)
 Late Effects: Infertility, secondary
malignancy, growth retardation.
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Key Points:
Chemotherapy is a major treatment in
curing or prolonging survival in cancer
patients
 It has a wide range of side effects
depending on the drugs given.
 Nurses have a key role to play in caring
for a patient receiving chemotherapy
 Safety issues are paramount in
administration.

Summary:
The potential benefit to the patient
of treatment as an option must
always outweigh the toxic effects.
Thank You
NCCN2012 Recommendations by
Risk Category
High (>90% emetic risk)
Including AC containing regimens
Three-drug combination of a HT3
serotonin receptor antagonist,
(palonosetron preferred-NCCN)
dexamethasone, and aprepitant
Moderate (>30% to 90% emetic
risk)
Two-drug combination of a HT3
serotonin receptor antagonist and
dexamethasone (+/-aprepitant for
selected patients)
Thank You
‫شاد باشید‬
Low (10% to 30% emetic risk)
Dexamethasone 8-12 mg
Minimal (<10% emetic risk
No antiemetic routinely