History of Chemotherapy

-Sidney Farber, a pathologist at Harvard

Medical School is regarded as the father
of modern chemotherapy.
 History of Chemotherapy
Pre 20th Century
1. 1500s– Heavy metals are used systematically to treat
cancers; however, that effectiveness is limited and their
toxicity is great.
2. 1890s– William Coley, MD, develops and explores the use
of Coley’s tonics, the first nonspecific immunostimulants
used to treat cancer.
World War I
1. Sulfur-mustard gas is used for chemical warfare;
servicemen who are exposed to nitrogenmustard
experience bone marrow and lymphnoid suppression.
 History of Chemotherapy
World War II
1. US Congress passes National Cancer Institute Act in 1937
(NCI)
2. Alkylating agents are recognized for their antineoplastic
effect
3. Thioguanine and mercaptopurine are developed
4. Research by NCI was started
5. Folic acid antagonists are found to be effective against
childhood acute leukemia
 History of Chemotherapy
1950s
1. National Chemotherapy Program, developed with
congressional funding, is founded to develop and test
new chemotherapy drugs
2. Interferon was discovered
3. The Children’s Cancer Group was started- cooperative
group dedicated to finding effective treatments for
pediatric cancer.
 History of Chemotherapy
1960s-1970s
1. Doxorubicin trial begins
2. Adjuvant chemotherapy begins to be a common cancer
treatment
1980s
1. Community Clinical Oncology Program are developed
2. Use of multimodal therapies increase
3. Research begins to investigate recombinant DNA
technology
4. Multiclonal antibodies and cytokines begin
 History of Chemotherapy
1990s
1. New classifications of drugs are developed
2. Clinical trials of gene therapy and antiangiogenic agents begin
3. The genetic basis of cancers become an important factor in cancer
risk research
2000s
1. Scientists complete a working draft of the human genome
2. Trials involving tumor necrosis factor, angiogenic inhibitors, and
monoclonal antibodies continue
3. FDA approves imatinib, the first molecularly targeted anticancer
drug, for use against chronic myelogenous leukemia
 History of Chemotherapy
Cancer drug development has exploded
since then into a multi-billion dollar
industry. The targeted therapy revolution
has arrived, but many of the principles and
limitations of chemotherapy discovered by
early researchers still apply.
 WHAT IS CANCER?
Large group of malignant diseases
with some or all of the ff
characteristics:
a. Abnormal cell proliferation
b. Lack of controlled growth and
division
c. Ability to metastasize
 WHAT IS CANCER?
-Afew diseases that result
from faulty or abnormal
genetic expression caused
by changes that have
occurred in the DNA.
 WHAT IS CANCER?

-The uncontrolled growth of

cells due to damage to DNA
(mutations) and,
ocassionally due to an
inherited propensity to
develop tumors.
 STAGING OF CANCER
Stage I – Tumor less than 2 cm, (-)
lymph node involvement, no
detectable metastases.

Stage II – Tumor greater than 2cm but

less than 5 cm, (-) or (+) unfixed lymph
node involvement, no detectable
metastases.
 STAGING OF CANCER

 Stage III – Large tumor greater than 5 cm,

or a tumor of any size with invasion of
the skin or chest wall or (+) fixed lymph
node involvement in the clavicular area
without incidence of metastases.

 Stage IV – Tumor of any size, (+) or (-)

lymph node involvement, and distant
metastases.
 Chemotherapy
 A systemic intervention used in the
treatment of certain disease
conditions
 In modern-day use, refers primarily to
the use of cytotoxic agents to treat
CANCER.
 CHEMOTHERAPEUTIC AGENTS-
Used only when disease prognosis
shows that patient would benefit from
the treatment
The Cell Cycle
• Broadly, most chemotherapeutic drugs
work by impairing mitosis (cell division),
effectively targeting fast-dividing cells.
• In cancer, cells rapidly divide and does
not enter the resting phase because they
are unresponsive to growth-inhibitory
signals.
• Only a percentage of the cancer cells are
killed with each course of chemotherapy.
Therefore, repeated doses—or cycles of
chemotherapy must be done.
SITES OF ACTION OF CYTOTOXIC AGENTS

Ant ibiotics

Ant imet abolites

S
(2-6h)
G2
(2-32h) Vinca alkaloids

M Mitotic inhibit ors

(0. 5-2h)

Taxoids

Alkylating agents

G1
(2-∞h)

G0
 GOALS
• CURE
Wilm’s Tumor
Hodgkuins Dse
Testicular c.
Acute Lymphoblastic
Leukemia
CONTROL
Breast
Ovarian
 Colon
Lung
Lymphoma
PALLIATION
Relieve Pain
Relieve Obstruction
Improve the sense of well-
being
 Chemotherapy may be used as

1.) Adjuvant therapy

-Refers to surgery followed by chemo- or radio
therapy to decrease the risk of cancer
recurring
2.) Neoadjuvant therapy
-First step in cancer treatment process
-It’s objective is to shrink a tumor before the
main treatment is given and bolster a
response to the main treatment
3.) Chemoprevention
-Use of drugs, Vitamins, or other agents
to reduce the risk or delay the
development of cancer
4.)Myeloablation
-Decreased activity of the bone marrow,
resulting in fewer red blood cells, and
platelets
-Also called myelosuppression
Classification of Chemotherapy
Drugs
CYCLE-SPECIFIC
Antimetabolites
interfere with nucleic acid synthesis
Attack during S phase of cell cycle
 Cytatabine, floxuridine, fluorouracil, hydroxyurea,
methotrexate, thioguanine
Enzymes
Useful only for leukemias
 Asparaginase
Plant Alkaloids
Cycle-specific to M Phase
Prevent mitotic spindle formation
 Vinblastine, vincristine
Classification of Chemotherapy
Drugs

CYCLE-NONSPECIFIC
 Alkylating Agents
› Disrupt deoxyribonucleic acid (DNA)
 Carboplatin, Cisplatin,
Cyclophosphamide, Ifosfamide, Thiotepa
 Antibiotics
› Bind with DNA to inhibit synthesis of
DNA and RNA
 Bleomycin, doxorubicin, idarubicin,
mitomycin, mitoxantrone
 Classification of Chemotherapy Drugs

CYTOPROTECTIVE AGENTS
Protect normal tissue by binding with metabolites
of other cytotoxic drugs
 Dexrazoxane
 Mesna

FOLIC ACID ANALOGS

Antidote for methotrexate toxicity
 Leucovorin
HORMONE AND HORMONE
INHIBITORS
› Interfere with binding of normal
hormones to receptor proteins
› Manipulate hormone levels
› After hormone environment
› Usually palliative,not curative
 Androgens, Antiandrogens,
Antiestrogens, Estrogens,
Gonadotropin, Progestins
 Other AntiCancer Agents
Novel Agents
Monoclonal Antibody
Trastuzumab (Herceptin)
Rituximab (Mabthera)
Cetuximab (Erbitux)
Tyrosine Kinase Inhibitor
Imatinib (Glivec)
EGFR Inhibitors
Erlotinib (Tarceva)
Gefitinib (Iressa)
VEGF Inhibitors
Bevacizumab (Avastin)
 BIOLOGICAL THERAPY
 Consists mostly of the administration of biological
response modifiers
 Also includes the use of immunotherapy
 Biological response modifiers
› Alter the body’s response to therapy
› May cause direct cytotoxicity
 Immunotherapy
› Uses drugs to enhance the body’s ability to destroy
cancer cells
› Seeks to evoke effective immune response to human
tumors by altering the way cells grow, mature, and
respond to cancer cells
› May include the administration of monoclonal
antibodies and immunomodulatory cytokines
 Immunotherapy
 Monoclonal antibodies
› Specifically target tumor cells
› More recent form of biotherapy that
manipulates the body’s natural resources
instead of introducing toxic substances
that aren’t selective and can’t
differentiate between normal and
abnormal processes or cells
› Recognizes only a single unique antigen
 Rituximab (Rituxan)
 Trastuzumab (Herceptin)
 Immunotherapy
 Immunomodulary cytokines
› Intracellular messenger proteins
(proteins that deliver messages
within cells)
 Colony-stimulating factors
 Erythropoietin (Epogen), Granulocyte colony-
stimulating factor (Neupogen), Granulocyte-
macrophage CSF (Leukine)
 Interferon
 Interleukins
 Tumor Necrosis factor
 Routes of Administration
• Oral Route
• Subcutaneous and Intramuscular
• IV administration
 IV push
 IV piggy back (large volume)
• Direct Introduction
 Intrathecal-Brain and spinal cord
 Intrapleural
 Intraperitoneal
 Chemoembolization-Blocking the blood supply to
the tumor, trapping the anti cancer drug at the site
and depressing the tumor of oxygen and nutrient
 Ommaya reservoir-Chemo direct to brain tumors
 Safehandling
Chemotherapeutic Agents
 Chemotherapeutic Drugs are hazardous
drugs.
 a hazardous drug is defined as an agent
that presents a danger to healthcare
personnel due to its inherent toxicity.
 They are carcinogenic
 They are mutagenic
 They are teratogenic
PREPARING CHEMOTHERAPEUTIC
DRUGS
• GATHERING THE EQUIPMENT
• Before preparing chemotherapeutic drugs, be sure to gather all the
necessary equipment, including:
– Patient’s medication order or record
– Prescribed drugs
– Appropriate diluent (if necessary)
– Medication labels
– Long-sleeved gown
– Chemotherapy gloves
– Face shield or goggles and face mask
– 20G needles
– Hydrophobic filter or dispensing pin
PREPARING CHEMOTHERAPEUTIC
DRUGS
GATHERING THE EQUIPMENT (continuation)
› Syringes with luer-lock fittings and
needles of various sizes
› IV tubing with luer-lock fittings
› 70% alcohol
› Sterile gauze pads
› Plastic bags with “hazardous drug”
labels
› Sharps disposal container
› Hazardous waste container
› Chemotherapy spill kit
PREPARING CHEMOTHERAPEUTIC
DRUGS
 ORGANIZING DRUG PREPARATION AREAS
› Prepare chemotherapeutic drugs in well-ventilated
workspace
› Perform all drug admixing or compounding within a
Class II Biological Safety Cabinet or a “vertical”
laminar airflow hood with a HEPA filter, which is
vented to the outside
› If a Class II Biological Safety Cabinet isn’t available, it
is recommended to use a special respirator
› Have close access to a sink, alcohol pads, and gauze
pads as well as Chemotherapy hazardous waste
containers, sharps containers, and chemotherapy
spill kits
 PREPARING CHEMOTHERAPEUTIC
DRUGS
ORGANIZING DRUG PREPARATION AREAS
(cont.)
– Make sure that all hazardous waste
containers are made of punctureproof,
shatterproof, leakproof plastic
– Make sure that yellow biohazard labels are
available for labeling all chemotherapy-
contaminated IV bags, tubings, filters, and
syringes
– Make sure that red sharps containers are
available for disposal of all contaminated
sharps such as needles.
 PREPARING CHEMOTHERAPEUTIC
DRUGS
WEAR PROTECTIVE CLOTHING
 Essential protective clothing includes a cuffed gown,
gloves, and a face shield or goggles and a face mask
 Gowns should be disposable, water-resistant, and
lint-free with long sleeves, knitted cuffs, and a closed
front
 Gloves should be disposable, powder-free, and made
of thick latex or thick nonlatex material
 Double gloving is an option when the gloves aren’t of
the best quality
 SAFETY MEASURES
GENERAL MEASURES
 At the local level, most health care
facilities require nurses and pharmacists
involved in the preparation and delivery
of chemotherapeutic drugs and care of
the patient with cancer.
 Take care to protect staff, patients and
the environment from unnecessary
exposure to chemotherapeutic drugs.
 SAFETY MEASURES
Make sure your facility’s protocols for
spills are available in all areas where
chemotherapeutic drugs are handled,
including patient-care areas
Refrain from eating, drinking,
smoking or applying cosmetics in the
drug-preparation area.
 SAFETY MEASURES
ACCIDENTAL EXPOSURE
 If a chemotherapeutic drug comes in
contact with your skin, wash the area
thoroughly with soap and water to
prevent drug absorption into the skin
 If the drug comes in contact with your
eye, immediately flush the eye with
water or isotonic eyewash for at least 5
minutes, while holding the eyelid open
 After an accidental exposure, notify your
supervisor immediately
 SAFETY MEASURES
WASTE DISPOSAL
› Place all contaminated needles in the sharps
container; don’t recap needles
› Use only syringes and IV sets that have a
luer-lock fitting
› Label all chemotherapeutic drugs with a
yellow biohazard label
› Transport the prepared chemotherapeutic
drugs in a sealable plastic bag that’s
prominently labeled with a yellow
chemotherapy biohazard label
› Don’t leave the drug-preparation area while
wearing the protective gear you wore during
drug preparation
 SAFETY MEASURES
HANDLING A
CHEMOTHERAPY SPILL
 Put on protective garments, if
you aren’t already wearing
them
 Isolate the area and contain the
spill with absorbent materials
from a chemotherapy spill kit
 Use the disposable dustpan
and scraper to collect broken
glass or desiccant absorbing
 SAFETY MEASURES
HANDLING A CHEMOTHERAPY
SPILL (cont’n)
 Carefully place the dustpan, scraper
 and collected spill in a leakproof,
punctureproof, chemotherapy-
designated hazardous waste container
 Prevent aerosolization of the drug at
all times
 Clean the spill area with a detergent
or bleach solution
ADMINISTERING CHEMOTHERAPEUTIC
DRUGS
• Gathering the equipment
– Prescribed drugs
– IV access supplies
– Sterile PNSS
– IV syringes and tubings with luer lock
– Leakproof chemical waste container
– Chemotherapy gloves
– Chemotherapy spill kit
– Extravasation kit
ADMINISTERING CHEMOTHERAPEUTIC
DRUGS

Preventing Infiltration
Use a low-pressure infusion pump to
administer vesicants through a
peripheral vein, to decrease the risk of
extravasation
Use a central venous catheter for
continuous vesicant infusions
 ADMINISTERING CHEMOTHERAPEUTIC
DRUGS
Guidelines in giving vesicants
 Use a distal vein that allows successive
proximal venipunctures
 Avoid using the hand, antecubital space,
damaged areas, or areas with
compromised circulation
 Don’t probe or “fish” for veins
 Place a transparent dressing over the
site
ADMINISTERING CHEMOTHERAPEUTIC
DRUGS
Guidelines in giving vesicants (cont’n)
 Start the push delivery or the
infusion with normal saline solution
 Inspect the site for swelling and
erythema
 Tell the patient to report burning,
stinging, pain, pruritus, or
temperature changes near the site
 After drug administration, flush the
line with 20mL of NSS
 ADMINISTERING CHEMOTHERAPEUTIC
DRUGS
Concluding Treatment
• Dispose of all used needles and contaminated
sharps in the orange sharps container
• Dispose of PPE’s in yellow chemotherapeutic
waste container
• Dispose of unused medications, considered
hazardous waste, according to your facility’s
policy
ADMINISTERING CHEMOTHERAPEUTIC
DRUGS
Concluding treatment (cont)
• Wash hands thoroughly
• Document the ff.
– sequence in which the drugs were administered
– site accessed, the gauge and length of the catheter, and
the number of attempts
– name, dose, and route of the administered drugs
– Type and volume of the IV solutions and adverse
reactions and nursing interventions
• According to facility policy, wear protective clothing when
handling body fluids from the patient for 48 hours after
MANAGING COMPLICATIONS OF
CHEMOTHERAPY

ALOPECIA
 Hair loss that occurs as chemotherapeutic drugs
destroy the rapidly growing cells of hair follicles
 May be minimal or severe
 Occurs 2-3 weeks after treatment begins
 Almost always temporary
Signs and Symptoms
 Hair loss that may include eyebrows, lashes and
body hair
Nursing Interventions
 Minimize shock and distress by warning the patient
of this possibility
 Discuss with the patient why it occurs
 Describe to the patient how much hair loss to expect
 Emphasize to the patient the need for appropriate
head protection against sunburn
 Inform the patient that new hair may be a different
texture or color
 Give the patient sufficient time to decide whether to
order a wig
 Inform the patient that his scalp will become sore at
times due to follicles swelling
Prevention measures
 For patients with long hair, suggest cutting hair
shorter before treatment because washing and
brushing cause more hair loss
ANEMIA
Occurs as chemo drugs destroy healthy cells and
cancer cells
RBCs are destroyed and can’t be replaced by the bone
marrow
Signs and symptoms
Dizziness, fatigue, pallor, and shortness of breath
after minimal exertion
Low hemoglobin level and hematocrit
May develop slowly over several courses of treatment
Nursing Interventions
Monitor hemoglobin level, hematocrit, RBC count;
report dropping values
Be prepared to administer a blood transfusion or
erythropoietin
Prevention Measures
Instruct the patient to take frequent rests, increase
his intake of iron-rich foods, and take a
multivitamin with iron as prescribed
If the patient has been prescribed a drug such as
epoetin, make sure he understands how to take the
drug and what adverse effects he should watch for
and report
DIARRHEA
 Occurs because the rapidly dividing cells of the
intestinal mucosa are killed
 Complications include weight loss, F&E
imbalance, and malnutrition
Signs and symptoms
 An increase in the volume of stool compared
with the patient’s normal bowel habits
Nursing Interventions
 Assess frequency, color, and consistency of stool
 Encourage fluids, give IV fluids and potassium
supplements as ordered
Prevention measures
 Use dietary adjustments and antidiarrheal meds
 Provide good perianal skin care
EXTRAVASATION
 The inadvertent leakage of a vesicant solution into
the surrounding tissue
Signs and Symptoms
 Initial signs and symptoms may resemble those of
infiltration – blanching, pain, swelling
 Symptoms possibly progressing to blisters; to skin,
muscle, tissue and fat necrosis; and to tissue
sloughing
Blood return is an INCONCLUSIVE test and
shouldn’t be used to determine if IV catheter is
correctly seated in the peripheral vein. To assess
peripheral IV placement, flush the vein with NSS
and observe site for swelling.
Extravasation of Doxorubicin
Nursing Interventions
 Stop the infusion
 Check your facility’s policy to determine if the IV
catheter is to be removed or left in place to infuse
corticosteroids or a specific antidote.
 Notify the physician
 Instill the appropriate antidote according to facility
policy. Usually, you’ll give the antidote for
extravasation either by instilling it through the
existing IV catheter or by using a 1 mL syringe to
inject small amounts subcutaneously in a circle
around the extravasated area
 After the antidote has been given, remove the IV
catheter
Preventive measures
Verify IV line patency and
placement by flushing with normal
saline sol’n
Remember, “When in doubt, take
it out!”
Use a transparent, semi-permeable
dressing for inspection of site.
INFILTRATION
The inadvertent leakage of a nonvesicant solution or
medication into the surrounding tissue
Infusion-site related
Signs and symptoms
Blanching
Change in IV flow rate
Numbness and tingling in swollen area due to nerve
compression injury leading to compartment
syndrome
Swelling around IV site (the swollen area will be cool
to touch)
Nursing Interventions
 Remove the IV catheter
 Insert a new IV catheter in a different
location
Prevention Measures
 Check for infiltration before, during,
and after the infusion by flushing the
vein with normal saline solution
LEUKOPENIA
Reduced leukocytes or WBCs
Occurs as WBCs and cancer cells are destroyed by
chemo drugs
Signs and Symptoms
Susceptibility to Infections
Neutropenia
Nursing Interventions
Watch for the nadir, the point of lowest blood cell
count
Be prepared to administer colony-stimulating
factors
Institute neutropenic precautions
Teach the patient and caregiver about:
Good hygiene practices
Signs and symptoms of infection
The importance of checking the patient’s
temperature regularly
How to prepare low-microbe diet
How to care for vascular access devices
Instruct the patient to avoid
Crowds
People with colds or respiratory infections
Fresh fruit
Fresh flowers
plants
NAUSEA and VOMITING
Can appear in 3 different patterns
Anticipatory
Acute
Delayed
ANTICIPATORY NAUSEA and VOMITING
Signs and Symptoms
 Nausea and vomiting that’s a learned response
from prior nausea and vomiting after a dose of
chemotherapy
 High anxiety levels (acts as a trigger)
Nursing Interventions
 Posttreatment control of nausea and vomiting
may prevent future anticipatory episodes
Prevention measures
 Pretreat the patient with lorazepam (Ativan)
at least 1 hr before arriving for treatment
 Patients with overwhelming anxiety may need
IV lorazepam before chemo is administered
ACUTE NAUSEA and VOMITING
Signs and symptoms
Nausea and vomiting occurring within the first 24
hours of treatment
Nursing Interventions
Treat the patient with acute nausea and vomiting
with antiemetic drugs
Dexamethasone
Granisetron
Lorazepam
Metoclopramide
Ondansetron
DELAYED NAUSEA and VOMITING
Signs and Symtoms
 Nausea or vomiting starting or continuing beyond
24 hours after chemo has begun
Nursing Interventions
 The administration of serotonin antagoninsts,
corticosteroids, various antihistamines,
benzodiapines, and and metoclopramide is usually
effective in treating patients
Prevention Measures
 Administer antiemetic before chemo begins
 Some patients with delayed nause and vomiting are
treated with an antiemetic for 3 days or longer
STOMATITIS
Inflammation of the lining of the oral
mucosa
Can spread into the esophagus and
pharynx
Signs and Symptoms
Painful mouth ulcers that range from
mild to severe appearing 3 to 7 days
after certain chemotherapeutic drugs
are given
Nursing Intervention
 Instruct the patient to perform meticulous oral
hygiene
 Administer topical anesthetic mixtures as
appropriate
 If pain is severe, opioid analgesics may be
prescribed until the ulcers heal
Prevention Measures
 Instruct the patient to suck on ice chips while
receiving certain drugs that cause stomatitis; this
decreases the blood supply to the mouth, thus
decreasing ulcer formation
THROMBOCYTOPENIA
Reduced blood platelet count
Signs and Symptoms
Bleeding gums
Coffee-ground emesis
Hematuria
Hypermenorrhea
Increased bruising
Petechiae
Tarry stools
Nursing interventions
Monitor patient’s platelet count
Avoid unnecessary IM injections or
venipuncture
If an IM injection or venipuncture is necessary,
apply pressure for at least 5 minutes; apply a
pressure to the site.
Instruct the patient to
Avoid cuts and bruises
Shave with an electric razor
Avoid blowing his nose
Stay away from irritants that would trigger sneezing
Avoid using rectal thermometers
Instruct the patient to report sudden headaches
(which could indicate potentially fatal intracranial
bleeding)
VEIN FLARE
 Occurs during infusion of an irritant into the vein
Signs and Symptoms
 Bright redness possibly appearing in the vein along
with blotches or hives on the affected arm
 Burning pain or aching along the vein as well as up
through the arm
Nursing Interventions
 If the reaction is severe, injection of an IV steroid
may be required
 If the patient complains of pain or burning during
the infusion:
› Increase the dilution of the infused medication
› Decrease the infusion rate
› Restart the IV in a different vein