Chemotherapy

History of Chemotherapy

-Sidney Farber, a pathologist at Harvard

Medical School is regarded as the father of modern chemotherapy.

History of ChemotherapyPre 20th Century1. 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 I1. Sulfur-mustard gas is used for chemical warfare;

servicemen who are exposed to nitrogenmustard experience bone marrow and lymphnoid suppression.

History of ChemotherapyWorld War II1. US Congress passes National Cancer Institute Act in 1937

(NCI)2. Alkylating agents are recognized for their antineoplastic

effect3. Thioguanine and mercaptopurine are developed4. Research by NCI was started5. Folic acid antagonists are found to be effective against

childhood acute leukemia

History of Chemotherapy1950s1. National Chemotherapy Program, developed with

congressional funding, is founded to develop and test new chemotherapy drugs

2. Interferon was discovered3. The Children’s Cancer Group was started- cooperative

group dedicated to finding effective treatments for pediatric cancer.

History of Chemotherapy1960s-1970s1. Doxorubicin trial begins2. Adjuvant chemotherapy begins to be a common cancer

treatment1980s1. Community Clinical Oncology Program are developed2. Use of multimodal therapies increase3. Research begins to investigate recombinant DNA

technology4. Multiclonal antibodies and cytokines begin

History of Chemotherapy1990s1. New classifications of drugs are developed2. Clinical trials of gene therapy and antiangiogenic agents begin3. The genetic basis of cancers become an important factor in cancer

risk research2000s1. Scientists complete a working draft of the human genome 2. Trials involving tumor necrosis factor, angiogenic inhibitors, and

monoclonal antibodies continue3. FDA approves imatinib, the first molecularly targeted anticancer

drug, for use against chronic myelogenous leukemia

History of ChemotherapyCancer 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 proliferationb. Lack of controlled growth and divisionc. Ability to metastasize

WHAT IS CANCER?-A few 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 CANCERStage 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 AGENTSSITES OF ACTION OF CYTOTOXIC AGENTS

Ant ibiotics

Ant imetabolites

S(2-6h)

G2

(2-32h)

M(0.5-2h)

Alkylating agents

G1

(2-∞h)

G0

Vinca alkaloids

Mitotic inhibitors

Taxoids

GOALS

• CUREWilm’s TumorHodgkuins DseTesticular c.Acute Lymphoblastic

Leukemia

CONTROLBreastOvarian ColonLungLymphoma

PALLIATIONRelieve Pain Relieve ObstructionImprove 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-SPECIFICAntimetabolites

interfere with nucleic acid synthesisAttack during S phase of cell cycle

Cytatabine, floxuridine, fluorouracil, hydroxyurea, methotrexate, thioguanine

EnzymesUseful only for leukemias

AsparaginasePlant Alkaloids

Cycle-specific to M PhasePrevent mitotic spindle formation

Vinblastine, vincristine

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 AGENTSProtect normal tissue by binding with metabolites

of other cytotoxic drugs Dexrazoxane Mesna

FOLIC ACID ANALOGSAntidote for methotrexate toxicity

Leucovorin

Classification of Chemotherapy Drugs

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 AgentsNovel AgentsMonoclonal Antibody

Trastuzumab (Herceptin)Rituximab (Mabthera)Cetuximab (Erbitux)

Tyrosine Kinase InhibitorImatinib (Glivec)

EGFR InhibitorsErlotinib (Tarceva)Gefitinib (Iressa)

VEGF InhibitorsBevacizumab (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 administrationIV push IV piggy back (large volume)• Direct IntroductionIntrathecal-Brain and spinal cordIntrapleuralIntraperitoneal 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 mutagenicThey 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 MEASURESMake 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 MEASURESACCIDENTAL 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 MEASURESWASTE 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 MEASURESHANDLING 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 powder

SAFETY MEASURESHANDLING 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 InfiltrationUse 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 temporarySigns 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 swellingPrevention measures For patients with long hair, suggest cutting hair

shorter before treatment because washing and brushing cause more hair loss

ANEMIAOccurs as chemo drugs destroy healthy cells and

cancer cellsRBCs are destroyed and can’t be replaced by the bone

marrowSigns and symptomsDizziness, fatigue, pallor, and shortness of breath

after minimal exertionLow hemoglobin level and hematocritMay develop slowly over several courses of treatment

Nursing InterventionsMonitor hemoglobin level, hematocrit, RBC count;

report dropping valuesBe prepared to administer a blood transfusion or

erythropoietinPrevention MeasuresInstruct 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 malnutritionSigns and symptoms An increase in the volume of stool compared

with the patient’s normal bowel habitsNursing Interventions Assess frequency, color, and consistency of stool Encourage fluids, give IV fluids and potassium

supplements as orderedPrevention measures Use dietary adjustments and antidiarrheal meds Provide good perianal skin care

EXTRAVASATION The inadvertent leakage of a vesicant solution into

the surrounding tissueSigns 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 measuresVerify 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.

INFILTRATIONThe inadvertent leakage of a nonvesicant solution or

medication into the surrounding tissueInfusion-site relatedSigns and symptomsBlanchingChange in IV flow rateNumbness 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

locationPrevention Measures Check for infiltration before, during,

and after the infusion by flushing the vein with normal saline solution

LEUKOPENIAReduced leukocytes or WBCsOccurs as WBCs and cancer cells are destroyed by

chemo drugsSigns and SymptomsSusceptibility to InfectionsNeutropeniaNursing InterventionsWatch for the nadir, the point of lowest blood cell

countBe prepared to administer colony-stimulating

factorsInstitute neutropenic precautions

Teach the patient and caregiver about:Good hygiene practicesSigns and symptoms of infectionThe importance of checking the patient’s

temperature regularlyHow to prepare low-microbe dietHow to care for vascular access devices

Instruct the patient to avoidCrowdsPeople with colds or respiratory infectionsFresh fruitFresh flowersplants

NAUSEA and VOMITINGCan appear in 3 different patterns

AnticipatoryAcuteDelayed

ANTICIPATORY NAUSEA and VOMITINGSigns 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 episodesPrevention 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 VOMITINGSigns and symptomsNausea and vomiting occurring within the first 24

hours of treatmentNursing InterventionsTreat the patient with acute nausea and vomiting

with antiemetic drugsDexamethasoneGranisetronLorazepamMetoclopramideOndansetron

DELAYED NAUSEA and VOMITINGSigns and Symtoms Nausea or vomiting starting or continuing beyond

24 hours after chemo has begunNursing 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

STOMATITISInflammation of the lining of the oral

mucosaCan spread into the esophagus and

pharynxSigns and SymptomsPainful 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 healPrevention 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

THROMBOCYTOPENIAReduced blood platelet countSigns and SymptomsBleeding gumsCoffee-ground emesisHematuriaHypermenorrheaIncreased bruisingPetechiaeTarry stoolsNursing interventionsMonitor patient’s platelet countAvoid 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 toAvoid cuts and bruisesShave with an electric razorAvoid blowing his noseStay away from irritants that would trigger sneezingAvoid 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 veinSigns 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 armNursing 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