Anticancer PSIK2007

8/8/2019 Anticancer PSIK2007

1/67

Anticancer Drugs

Nur Permatasari


2/67

CANCER

Refers to a Malignant neoplasm (New growth)

Cancer cells can manifest:

Uncontrolled Proliferation. Loss of function due to lack of ability to differentiate. Do not die on schedule


3/67

Causal Factors

According to etiologic factors

Chemical

Familial Physical

Viral

According to environmental factors

Occupational

Dietary Lifestyle

Environmental


4/67

Chemical Carcinogenesis

Carcinogens are rich in electrons (free radicals) that bindto DNA causing mutations

1915 First laboratory carcinogenesis Coal tar applied to rabbit skin

1761 Discovery: tobacco contains carcinogens

1775 Soot causes testicular cancer in chimney sweeps

1930 First synthetic carcinogen discovered

There are now thousands 1950 Tobacco rediscovered as carcinogen

Chemotherapy is carcinogenic Alkylating agents worst


5/67

Familial Carcinogenesis

Up to 15% of all tumors have hereditary component

Breast Cancer -13%

BRCA1 breast and ovarian cancer

BRCA2 breast cancer

Colorectal Cancer 5%

Dysplastic Nevi syndrome melanoma

35 familial cancer syndromes have been published Loss of tumor-suppressor gene


6/67

Physical Carcinogenesis

Damage to genes is physical

Ionizing radiation

Leads to permanent mutations in DNA Radon much publicized but little data

Ultraviolet radiation

Induces DNA change that leads to malignanttransformation

Asbestos inhalation Synergistic with tobacco smoke

Mechanism of action unknown

Causes mesotheliomas and bronchogenic cancers


7/67

Viral Carcinogenesis

Earliest viral oncogene found in 1911

Caused Sarcoma in chickens

Viral infections DO NOT produce malignancy multi-stepprocess

Human T-cell leukemia virus type 1 (HTLV1) implicated inadult T-cell leukemia

Hep B - Hepatocellular cancer

Hep C - Hepatoma Epstein-Barr virus Burkitts lymphoma

Human Papillomaviruses (HPV) cervical and othergenital cancers


8/67

Bacterial Carcinogenesis

Mucosa-Associated Lymphoid Tissue (MALT) cancer

Helicobacter pylori (H. pylori)

Treat the H.pylori and you get rid of MALT

Chronic H. pylori gastritis associated with an increased riskof gastric carcinoma.


9/67

Principles of Cancer Treatment Cure - Disease gone forever Control - Extend life of patient; disease will never go away

completely Palliation - Provide comfort, relief of symptoms, and

improve quality of life Prophylaxis - No disease but person at high risk for

disease development

Cure & control: Surgery Radiotherapy -Antineoplastic drug


10/67


11/67

R

Tumor Suppressor

Genes -ve (p53)

Growth Factors

Oncogenes +ve

SDNA

Synthesis

G2Premitotic

Interval

M

PROPHASEMETAPHASE

ANAPHASE

TELOPHASE

MITOSIS

G0G1

S PHASESPECIFICArbinoside

HydroxyureaS PHASE

SPECIFIC

SELFLIMITING6-MercaptpurineMethotrexate.

M PHASESPECIFICvincristinevinblastinepaclitaxel

PHASE NONSPECIFICalkylating agents, cis-platinumnitrosoureas, dacarbazineAntibiotics

G0

Differentiation


12/67

CELL GROWTH CYCLE5 DISTINCT PHASES OF MITOSIS

1. G0 - Resting - no mitosis2. G1 - Postmitotic - first growth3. S - DNA synthesis phase4. G2 - Premitotic - second growth

5. M - Mitosis phaseGENERATION TIME - one complete cycle differentin all tumors, from hours to days


13/67

ANTINEOPLASTIC AGENTS2 MAIN GROUPS OF AGENTS:

CELL CYCLE - NONSPECIFIC (CCNS)

ALKYLATING AGENTScytotoxic in any phase of cell cycleeffective against slowly growing tumors

CELL CYCLE - SPECIFIC (CCS) 3 TYPES

ANTIMETABOLITES - cytotoxic is S phaseMITOTICINHIBITORS - cytotoxic in M phaseCYTOTOXIC ANTIBIOTICS (some are CCNS)

effective against rapidly growing tumors


14/67

PENTOSTATIN

Inhibits adenosine

Deaminase

PALA

Inhibits PyrimidineBiosynthesis

Purine

synthesis

Pyrimidine

synthesis

Ribonucleotides

Deoxyribonucleotides

DNA

HYDROXYUREA

Inhibit

Ribonucleotide

Reductase

6-MERCAPTOPURINE

6-THIOGAUNINEInhibit Puring ring

biosynthesis

Inhibit Neocleotide

interconversions

5-FLOUROURACIL

Inhibit TMP

Synthesis

METHOTREXATEInhibit dihydrofolate

reduction, blocks

TMP and Purine

synthesis


15/67

DNA

RNA

(Transfer, messenger, ribosomal)

CYTARABINE

FLUDARABINE

2-CHLORODEOXY

ADENOSINE

Inhibit DNA

Synthesis

ALKYLATING AGENTS

MITOMYCETINCISPLATIN

PROCARBAZINE

DACARBAZINE

Form adducts w/ DNA

BLEOMYCIN

ETOPOSIDE

TENIPOSIDEDamage DNA and

Prevent repair

DACTINOMYCINE

DAUNORUBICINDOXORUBICIN

MITOXANTRONE

Intercalate with DNA

Inhibit RNA synthesis

PROTEINS

Enzymes Microtubules

A-ASPARAGINASEDeaminate

asparagine

Inhibits protein

synthesis

PACLITAXELVINCA ALKALOIDS

COLCHICINE

Inhibit function of

Microtubules


16/67

ANTINEOPLASTIC AGENTS

ADVERSE EFFECTS:

Kills all fast growing cells Hair follicles

GI tract mucosa Bone marrow suppression (BMS)

causing anemia, thrombocytopenia and leukopenia Nephro- hepato- cardio- neoro and ototoxic Extravasation of IV can result in tissue damage


17/67

Antineoplastic Agents

ADVERSE EFFECTS: (Contd)

All have an emetic index All have wide interaction with other drugs.


18/67

ALKYLATING AGENTSNITROGEN MUSTARDS first developed in 1940s

CCNS killing abilitymechlorethamine is the prototypical agent

USES: Hodgkins disease & lymphomas.leukemias,

CANCERS OFlung,breast,ovary,

testes,brain,bladder,

Most widely used agent, often in combination with otheragents.


19/67

ALKYLATING AGENTS

SELECTED AGENTS:

Mechlorethamine (Mustine, Mustargen)IV only (adult use only)

Cyclophosphamide (Cytoxan, Neosar)IV and PO, adults and pediatric use

Carmustine (BiCNU)

IV, adult only, can cross blood-brain barrier,therefore used to tread brain lesions

OTHER AGENTS: Chlorambucil, Streptozotocin


20/67

ANTIMETABOLITESACTIONS:Antagonism of folate,purines, and pyrimidines needed for synthesis of nucleicacids -stops cell replication

USES:Solid tumors

(breast, lung, liver, brain, colon. Stomach, pancreas)Lymphomas, leukemias.Some agents also immunosuppressive,Useful in treating immune-mediated diseases


21/67

ANTIMETABOLITESSELECTED AGENTS: (FOLIC ACID ANALOG) METHOTREXATE (Folex, Rheumatrex, MTx) Folic acid antagonist

PO & IM, adult and pediatric use Also used to treat immune-mediated diseases, Used incombination with misoprostol for therapeutic

abortion Causes profound anemia (folate depletion)

Therefore leucovorin rescue often used tocounteract


22/67

ANTIMETABOLITESSELECTED AGENTS:

PURINE ANALOG

- MERCAPTOPURINE (6-MP, Purinethol)- Purine antagonist- PO only, adult and pediatric use

PYRIMIDINE ANALOG -CYTARABINE (Ara-C, Cytosar-U)

-Pyrimidine antagonist-IV and intrathecal (within spinal canal)


23/67

MITOTICINHIBITORSACTIONS:Plant alkaloids (periwinkle, yew tree, mandrake plant, etc.)

Bind to and disrupt mitotic spindles

USES:Lymphomas (Hodgkins and non-Hodgkins),NeuroblastomaKaposis sarcoma,Solid tumors (breast, testicular, etc.)


24/67

MITOTICINHIBITORSSELECTED AGENTS:

ETOPOSIDE (VP-16, VePesid)IV

and PO, adult use onlyPACLITAZEL(Taxol)IV only, adult use onlydrug of choice for ovary and breast ca

VINCRISTINE (LCR, VCR,Oncovin)IV only, adult and pediatric usedrug of choice for acute leukemia


25/67

CYTOTOXIC ANTIBIOTICSACTIONS: Source: Streptomyces mold - work by intercalation

(insertion of drug molecule between the 2 DNA strandscausing it to (unwind) Kill some bacteria and viruses but are too toxic to use forinfections

IV extravasation constant danger !USES:wide variety of solid tumors,always used in combination with other agents


26/67

CYTOTOXIC ANTIBIOTICS

SELECTED AGENTS:

DOXORUBICIN (ADR, Rubex, Doxil)IV only, adult use only

BLEOMYCIN (BLM, Blenoxane)IM, IV, SQ, adult use only

very toxic agents !!!


27/67

MISCELLANEOUS ANTINEOPLASTICSVarious actions,Both CCNS and CCSUsed in combinations with other agents

SELECTED AGENTS:

Cisplatin (Platinol)IV, adult and pediatric use

ALTRETAMINE (Hexalen)PO only, adult use only, primarily used to treat ovarian cancer

ASPARAGINASE (Elspar)IV

only, adult and pediatric useHYDROXYUREA (Hydrea)PO only, adult use only


28/67

MISCELLANEOUS ANTINEOPLASTICSHORMONES AND ANTAGONISTS.

1. Adrenocortical Suppressant:Mitotane, Aminoglutethimide. (Adrenal Cortex)

2.Adrenocortical Steroids.Prednisone. (Lukemias, Lymphomas, Breast)

3.Progestins.

Hydroxyprogestrone.(Endometrium, (Breast)Medroprogestrone, Megesterol acetate.4.Estrogens.

DES, Ethinylesterdiol.(Breast, Prostate)5.Antiestrogens.

Tamoxifen .(Breast)6.Androgens. Testosterone (Breast)7.Antiandrogens. Flutamide (Prostate).8.Gonadotropin Releasing Hormone Analog.

Leuprolide. (Prostate)


29/67

NURSING MANAGEMENT

- Before chemotherapy program asses physical

status and baseline data

- Monitor the results of a variety oflaboratory test

~ which test are necessary depend on the drugs

(bone marrow suppression, cardiotxic, nephrotoxic,

neurotoxic, ototoxic, hepatotoxic)


30/67

PLANNING

Decrease anxiety, understand of thechemotherapy program, adaptation to changes in

body appereance and function, absence of thevariety of injury, absence of diarrhea/constipation, maintanance of oral mucousmembrane integrity, maintanance of optimalnutritional status, maintanance of fluid and

electrolyte balance, achievement of maximalphysical mobility, peformance of self careactivities within physical limitations


31/67

INTERVENTIONS-Body image disturbance (alopecia-High risk for infection ~ bone marrow supp.-High risk for nephrotoxicity

-Altered oral mucous membrane-Altered nutrition-High risk for drug extravasation (tissuedamage,loss of function, infection, necrosis)Antidotum:10% sodium thiosulfate ~

mechloretamine, pyridoxine~ mitomycin,hyaluronidase and warming ~ vinca alcaloids,dimethyl sulfoxide ~ daunorubicin/doxorubicin)


32/67


33/67

Treatment of Extravasation

AT FIRST SIGN, stop chemo

Attempt to aspirate residual drug

Remove IV Notify physician

Administer antidote (if ordered)

Heat/Cold as appropriate

Elevate extremity Document extravasation and management


34/67

Local Reactions from ChemotherapyAdministration

Extravasation: leakage or infiltration of a vesicantchemotherapy agent into local tissue

Vesicant: any agent that has the potential to cause blisteringor tissue necrosis

Irritant: any agent that causes a local inflammatory reactionbut does not cause tissue necrosis

Flare reaction: venous inflammatory response with

subsequent histamine release that may result in flarereaction; incidence is usually about 3% and duration usuallyless than 45 minutes


35/67

Local Reactions


36/67


37/67

Risk of Infection

ANC of > 1000 = No risk of infectionANC 500 to 1000 = Mild to moderate risk

ANC < 500 = Severe risk of infection

The longer severe neutropenia lasts, the greaterthe risk of a life-threatening infection


38/67

Assessment

FEVER is most important sign of infection

Monitor ANC

Look for pain, redness at wound sites, open areas,frequent urination, mental status changes

Assess head to toe

Teach patient to observe for signs of infection

Take temperature at least once q 24 hours

Call if > 100.4

Go to ER if > 102 and mental status changes


39/67

Management of Neutropenia

Temperatures q 4 hours around the clock

Limit Tylenol; can mask fever

Cultures done with first fever (before abx) First antibiotic given as STAT dose ( ~ 1 hr)

Monitor vital signs frequently - sepsis kills rapidly

New or continued fevers

May need to change antibiotic

May need to add anti-fungal agent

Temp should drop 1 degree in 24 hrs and be gone after 48hours if abx is working


40/67

Neutropenic Precautions

NOT reverse isolation

Controversial whether infection risk is lowered

Private room No fresh fruits or vegetables to eat

No live plants/flowers/standing water

No sick visitors or caregivers

No small children (very controversial) No caregivers taking care of other infected pts

Pt wears mask when out of room


41/67

Thrombocytopenia

Decreased number of platelets

Risk of bleeding increases below 50,000 Risk of bleeding substantial under 20,000

Transfusions may not be done until 10-15,000

risk of auto-immunizing patient


42/67

Management

Assess head to toe for bleeding/petechiae

Monitor platelet count

Teach patient to report signs of bleeding orincreased petechiae

Transfuse as ordered (pre-medicate usually)


43/67

Bleeding Precautions

NO ASA or NSAIDS

Nothing inserted into rectum or vagina

No foley catheters if at all possible

No IM injections

Limit venipunctures and invasive procedures

Soft toothbrush-no flossing - electric razor No vigorous exercise

Avoid straining at stool


44/67

Anemia

Decreased number of red blood cells

Transfusions given when Hgb < 8, Hct < 24 or

patient is symptomatic

Elderly patients or those with history of cardiacproblems may not tolerate anemia

Epogen (Procrit) given to stimulate RBC production

Helps combat fatigue


45/67

Fatigue

Multiple causes

Most common side effect from chemo

Not relieved by sleep

Prevention of anemia can reduce incidence

Short periods of mild exercise can reduce severity

Teach energy conservation and appropriate restperiods

Need for caregiver assistance


46/67

Nausea & Vomiting

Stimulation of vomiting center (brain) bychemo-receptor trigger zone (CTZ), vagal

stimulation, seratonin, etc.

Most distressing side effect of chemo

Acute, delayed, anticipatory

Not all chemo drugs have same emeticpotential


47/67

Emesis Induced by Therapeutic Interventions

Cancer Chemotherapy-induced emesis

Radiotherapy-induced emesis

Postoperative emesis


48/67

Types of Emesis in PatientsReceiving Cancer Chemotherapy

Type Onset

e24 h postchemotherapy

>24 h postchemotherapy

Before administration of

chemotherapy

Acute emesis

Delayed emesis

Anticipatory nausea/

vomiting


49/67

Adapted from Mitchell and Schein. Toxicity of Chemotherapy. 1984:271.

The Physiology of Emesis

Cerebral

Cortex

Chemoreceptor Trigger Zone

Vomiting Center

EFFERENT PATHWAYS

Vagi

Sympathetics

Phrenics


50/67

Proposed Mechanism of Cancer

Chemotherapy-Induced Emesis

Cytotoxin triggers release of serotonin fromenterochromaffin cells in the gastrointestinal tract

Serotonin stimulates nerve receptors that project toand activate the vomiting center

In humans, urinary 5-HIAA (5 hydroxyindo-leaceticacid, a metabolite of serotonin) excretion increasesafter cisplatin administration in parallel with the onsetof emesis; the released serotonin may stimulate vagalafferents through the 5-HT3 receptors, thereby initiatingthe vomiting reflex


51/67

Emetogenic Potential of

Chemotherapy Drugs Very High (5)

Cisplatin

Nitrogen Mustard

High (4)

Cytoxan (HD)

Ara-C (HD)

Methotrexate (HD)

Moderate (3) Etoposide (VP-16)

Ifosfamide

Ara-C

Moderate (cont)

Carboplatin

Methotrexate

Low (2)

Bleomycin

Taxanes

5-FU

Doxil Very Low (1)

Vinca Alkaloids

Methotrexate (LD)


52/67

Anti-emetics

5HT3 blocker

Ondansetron (Zofran)

Granisetron (Kytril)

Dolasetron (Anzemet)

Benzamide

Metaclopramide

(Reglan)

Phenothiazides

Compazine

Thorazine

Corticosteroids

Decadron

Butyrophenones

Haldol

Cannabinoids

Marinol

Miscellaneous

Lorazepam (Ativan)

Benedryl


53/67

Management of N&V

Very sensitive to smells (may be abnormal)

TAKE antiemetics as ordered

Room temperature or cold foods smell less

Frozen juice or popsicles are soothing

Avoid fatty, greasy, spicy, sweet foods

Eat small meals

Avoid favorite foods at this time


54/67

Anorexia

Taste changes last ~ 1 week

Smells become acute; lasts 1-3 weeks

Mild exercise or wine may stimulate appetite

Avoid too much liquid near mealtime

Eat high calorie, nutritious foods

Avoid junk food

Use supplements as needed

Megace can stimulate appetite (> 350 mg/day)


55/67

Diarrhea

Increase in liquidity and frequency of stools(> 3 stools above usual amount)

Destruction of epithelium of GI tract Related to medication, dose and frequency

Worse with RT to abdomen/gut area

Drugs: Camptosar, Methotrexate, 5-FU

May be dose-limiting toxicity of drug

May be concommitant infection (C. diff)


56/67

Management of Diarrhea

Camptosar: treat early diarrhea with Atropine andlate diarrhea with Immodium--prophylactically

BRAT diet -- low residue diet -- clear liquids Avoid milk products

Scrupulous peri care; keep area dry

Use moisture barrier cream (Desitin)

Use anti-diarrheals: Lomotil, Immodium,Kaopectate, Pepto-bismol, Sandostatin (last resort)


57/67

Constipation

Infrequent hard, dry, bowel movements thatmay cause pain or bleeding

Vinca Alkaloids - Vincristine worst

Other reasons: dehydration, no activity,opioid use, low residue diet

May cause bloating, pain, N&V, obstructionor ileus, rectal bleeding, hemorrhoids, tears


58/67

Management of Constipation

Treat prophylactically

Adequate fluid intake

Increased fiber intake

Increased activity

Stool softeners taken routinely (Senekot)

Laxative or Cathartic if no BM in 3 days Try to avoid enemas


59/67

Stomatitis/Mucositis

Inflammation or ulceration of mouth which canprogress to entire GI tract

Destruction of fast-growing epithelial cells

Drugs: 5-FU, Methotrexate, Xeloda, Bleomycin, HDchemo

Radiation fields that include mouth or throat

Alcohol, tobacco use

Poor oral hygiene, dental caries

Causes pain, infection, dehydration, weight loss


60/67


61/67

Management of Mucositis

Daily/Bid oral assessment

Frequent (q 2 hr) mouth care

NS rinse (avoid alcohol-containing mouthwash)

Brush with soft toothbrush--also brush tongue

Keep lips and mouth moist

Soft diet with high caloric bland foods

Topical anesthetic agents

Treat infections quickly

PREVENTION is best


62/67

Alopecia

Temporary - begins in 2 to 3 weeks

Hair regrows 4 to 6 weeks after chemo

Texture and color may be different in new hair Degree of alopecia related to drug, dose,

schedule, and amount of hair patient hadprior to chemo

MOST distressing symptom

May be equally distressing for men and women


63/67

Management of Alopecia

PATIENT TEACHING is very important

May lose hair on entire body (taxanes, high dose

chemo or total body radiation) Cut hair short to reduce irritation from shedding

Wig or headcovering resources available-may beinsurance benefit--can get script for wig

Wear headcovering to reduce temperature loss

Protect scalp from sun (may be photosensitive)


64/67

Photosensitivity

Increased skin sensitivity to UV exposure

Drugs causing: 5-FU, Methotrexate, Taxol,

Adriamycin, Vincristine Sunburn with blisters and erythema;

hyperpigmentation

Avoid tanning booths, sunbathing even on cloudy

days Wear sunscreen (> 15 spf) or protective clothing


65/67


66/67

Sexual Side Effects

Related to drug, dose, length of treatment, age andsex of patient

Men: impotence, decreased libido, hot flashes,decreased sperm count, gynecomastia, body imagechanges

Women: irregular or no menses, vaginal dryness,

decreased ova production, painful intercourse,decreased libido, hot flashes, body image changes


67/67

Management

Patient education

Discuss concerns frankly Sperm banking

Birth control

Lubrications

Position changes

Counseling (time of high stress)

Anticancer PSIK2007

Documents

Transcript of Anticancer PSIK2007