Anticancer Drugs

Nur Permatasari
“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
 Causal Factors

 According to etiologic factors

 Chemical

 Familial

 Physical

 Viral

 According to environmental factors

 Occupational

 Dietary

 Lifestyle

 Environmental
 Chemical Carcinogenesis

 Carcinogens are rich in electrons (free radicals) that bind

to 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
 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

 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 malignant

transformation
 Asbestos inhalation
 Synergistic with tobacco smoke

 Mechanism of action unknown

 Causes mesotheliomas and bronchogenic cancers

 Viral Carcinogenesis

 Earliest viral oncogene found in 1911

 Caused Sarcoma in chickens

 Viral infections DO NOT produce malignancy – multi-step

process
 Human T-cell leukemia virus type 1 (HTLV1) implicated in
adult T-cell leukemia
 Hep B - Hepatocellular cancer
 Hep C - Hepatoma
 Epstein-Barr virus – Burkitt’s lymphoma
 Human Papillomaviruses (HPV) – cervical and other
genital cancers
 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 risk

of gastric carcinoma.
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
Cell Cycle
 M
G2 M PHASE
PROPHASE
S PHASE Premitotic METAPHASE
SPECIFIC
SPECIFIC Interval ANAPHASE
vincristine
Arbinoside TELOPHASE
S
Hydroxyurea
S PHASE
vinblastine
paclitaxel
MITOSIS
DNA
SPECIFIC
Synthesis
SELF LIMITING
6-Mercaptpurine
Methotrexate.

PHASE NONSPECIFIC
• Tumor Suppressor
alkylating agents, cis-platinum
Genes -ve (p53)
nitrosoureas,
• Growth Factors dacarbazine G 1 G0 G0
Antibiotics
Oncogenes +ve R Differentiation
CELL GROWTH CYCLE
5 DISTINCT PHASES OF MITOSIS

1. G0 - Resting - no mitosis
2. G1 - Postmitotic - first growth
3. S - DNA synthesis phase
4. G2 - Premitotic - second growth
5. M- Mitosis phase
GENERATION TIME - one complete cycle different
in all tumors, from hours to days
ANTINEOPLASTIC AGENTS
2 MAIN GROUPS OF AGENTS:

CELL CYCLE - NONSPECIFIC (CCNS)

ALKYLATING AGENTS
cytotoxic in any phase of cell cycle
effective against slowly growing tumors

CELL CYCLE - SPECIFIC (CCS) 3 TYPES

ANTIMETABOLITES - cytotoxic is S phase
MITOTIC INHIBITORS - cytotoxic in M phase
CYTOTOXIC ANTIBIOTICS (some are CCNS)
effective against rapidly growing tumors
 PENTOSTATIN Purine Pyrimidine PALA
synthesis synthesis
Inhibits adenosine Inhibits Pyrimidine
Deaminase Biosynthesis

Ribonucleotides
6-MERCAPTOPURINE HYDROXYUREA
6-THIOGAUNINE
Inhibit Puring ring Inhibit
biosynthesis Ribonucleotide
Deoxyribonucleotides
Inhibit Neocleotide Reductase
interconversions

METHOTREXATE 5-FLOUROURACIL
Inhibit dihydrofolate
Inhibit TMP
reduction, blocks
Synthesis
TMP and Purine
synthesis DNA
 BLEOMYCIN CYTARABINE
ETOPOSIDE FLUDARABINE
TENIPOSIDE 2-CHLORODEOXY
DNA ADENOSINE
Damage DNA and
Prevent repair Inhibit DNA
Synthesis

DACTINOMYCINE ALKYLATING AGENTS

DAUNORUBICIN MITOMYCETIN
DOXORUBICIN CISPLATIN
MITOXANTRONE PROCARBAZINE
Intercalate with DNA RNA DACARBAZINE
Inhibit RNA synthesis (Transfer, messenger, ribosomal) Form adducts w/ DNA

A-ASPARAGINASE PACLITAXEL
Deaminate VINCA ALKALOIDS
asparagine PROTEINS COLCHICINE
Inhibits protein Inhibit function of
synthesis Microtubules
Enzymes Microtubules
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
Antineoplastic Agents

ADVERSE EFFECTS: (Contd)

• All have an emetic index

• All have wide interaction with other drugs.
ALKYLATING AGENTS
NITROGEN MUSTARDS first developed in 1940s

CCNS killing ability

mechlorethamine is the prototypical agent
USES: Hodgkin’s disease & lymphomas.
leukemias,
CANCERS OF
lung,
breast,
ovary,
testes,
brain,
bladder,
Most widely used agent, often in combination with other
agents.
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
ANTIMETABOLITES
ACTIONS:
•Antagonism of folate,
•purines, and pyrimidines needed for synthesis of nucleic
acids -
•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
ANTIMETABOLITES
SELECTED 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 to
counteract
ANTIMETABOLITES
SELECTED 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)
MITOTIC INHIBITORS
ACTIONS:
Plant alkaloids (periwinkle, yew tree, mandrake plant, etc.)
Bind to and disrupt mitotic spindles

USES:
Lymphomas (Hodgkin’s and non-Hodgkin’s),
Neuroblastoma
Kaposi’s sarcoma,
Solid tumors (breast, testicular, etc.)
MITOTIC INHIBITORS
SELECTED AGENTS:
ETOPOSIDE (VP-16, VePesid)
IV and PO, adult use only
PACLITAZEL (Taxol)
IV only, adult use only
drug of choice for ovary and breast ca
VINCRISTINE (LCR, VCR,Oncovin)
IV only, adult and pediatric use
drug of choice for acute leukemia
CYTOTOXIC ANTIBIOTICS
ACTIONS:
• Source: Streptomyces mold - work by intercalation
(insertion of drug molecule between the 2 DNA strands
causing it to (“unwind”)
• Kill some bacteria and viruses but are too toxic to use for
infections
IV extravasation constant danger !
USES:
wide variety of solid tumors,
always used in combination with other agents
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 !!!
MISCELLANEOUS ANTINEOPLASTICS
Various actions,
Both CCNS and CCS
Used 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 use
•HYDROXYUREA (Hydrea)
PO only, adult use only
MISCELLANEOUS ANTINEOPLASTICS
HORMONES 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)
NURSING MANAGEMENT

- Before chemotherapy program asses physical

status and baseline data
- Monitor the results of a variety of laboratory test
~ which test are necessary depend on the drugs
(bone marrow suppression, cardiotxic, nephrotoxic,
neurotoxic, ototoxic, hepatotoxic)
PLANNING

Decrease anxiety, understand of the

chemotherapy program, adaptation to changes in
body appereance and function, absence of the
variety of injury, absence of diarrhea/
constipation, maintanance of oral mucous
membrane integrity, maintanance of optimal
nutritional status, maintanance of fluid and
electrolyte balance, achievement of maximal
physical mobility, peformance of self care
activities within physical limitations
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 (tissue
damage,loss of function, infection, necrosis)
Antidotum:10% sodium thiosulfate ~
mechloretamine, pyridoxine~ mitomycin,
hyaluronidase and warming ~ vinca alcaloids,
dimethyl sulfoxide ~ daunorubicin/doxorubicin)
 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
Local Reactions from Chemotherapy
Administration
 Extravasation: leakage or infiltration of a vesicant
chemotherapy agent into local tissue
 Vesicant: any agent that has the potential to cause blistering
or tissue necrosis
 Irritant: any agent that causes a local inflammatory reaction
but does not cause tissue necrosis
 Flare reaction: venous inflammatory response with
subsequent histamine release that may result in flare
reaction; incidence is usually about 3% and duration usually
less than 45 minutes
Local Reactions
Neutropenia

 Decreased number of granulocytes

 Granulocytes - one of the white blood cells
 Absolute neutrophil count (ANC) = number of
granulocytes in the blood.
 Measures the first line of defense against infection
 ANC = total WBC x (% polys + % bands)
example: 5000 x ( 40% + 10%) = 2,500
Risk of Infection

 ANC of > 1000 = No risk of infection

 ANC 500 to 1000 = Mild to moderate risk
 ANC < 500 = Severe risk of infection

 The longer severe neutropenia lasts, the greater the

risk of a life-threatening infection
 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

 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 48

hours if abx is working

 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
 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
 Management

 Assess head to toe for bleeding/petechiae

 Monitor platelet count
 Teach patient to report signs of bleeding or
increased petechiae
 Transfuse as ordered (pre-medicate usually)
 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
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 cardiac
problems may not tolerate anemia
 Epogen (Procrit) given to stimulate RBC production
 Helps combat fatigue
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 rest
periods
 Need for caregiver assistance
Nausea & Vomiting

 Stimulation of vomiting center (brain) by

chemo-receptor trigger zone (CTZ), vagal
stimulation, seratonin, etc.
 Most distressing side effect of chemo
 Acute, delayed, anticipatory
 Not all chemo drugs have same emetic
potential
Emesis Induced by Therapeutic Interventions

 Cancer Chemotherapy-induced emesis

 Radiotherapy-induced emesis
 Postoperative emesis
Types of Emesis in Patients
Receiving Cancer Chemotherapy

Type Onset
Acute emesis  24 h postchemotherapy

Delayed emesis >24 h postchemotherapy

Anticipatory nausea/ Before administration of

vomiting chemotherapy
 The Physiology of Emesis

Cerebral Cortex

Chemoreceptor Trigger Zone

Vomiting Center

EFFERENT PATHWAYS
Vagi
Sympathetics
Phrenics

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

 Proposed Mechanism of Cancer
Chemotherapy-Induced Emesis

 Cytotoxin triggers release of serotonin from

enterochromaffin cells in the gastrointestinal tract
 Serotonin stimulates nerve receptors that project to
and activate the vomiting center
 In humans, urinary 5-HIAA (5 hydroxyindo-leacetic
acid, a metabolite of serotonin) excretion increases
after cisplatin administration in parallel with the onset
of emesis; the released serotonin may stimulate vagal
afferents through the 5-HT3 receptors, thereby
initiating the vomiting reflex
Emetogenic Potential of
Chemotherapy Drugs
 Very High (5)  Moderate (cont)
 Cisplatin  Carboplatin
 Nitrogen Mustard  Methotrexate
 High (4)  Low (2)
 Cytoxan (HD)  Bleomycin
 Ara-C (HD)  Taxanes
 Methotrexate (HD)  5-FU
 Moderate (3)  Doxil
 Etoposide (VP-16)  Very Low (1)
 Ifosfamide  Vinca Alkaloids
 Ara-C  Methotrexate (LD)
 Anti-emetics

 5HT3 blocker  Corticosteroids

 Ondansetron (Zofran)  Decadron
 Granisetron (Kytril)  Butyrophenones
 Dolasetron (Anzemet)  Haldol
 Benzamide  Cannabinoids
 Metaclopramide  Marinol
(Reglan)  Miscellaneous
 Phenothiazides  Lorazepam (Ativan)
 Compazine  Benedryl
 Thorazine
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
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)
 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)
Management of Diarrhea

 Camptosar: treat early diarrhea with Atropine and

late 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)
Constipation

 Infrequent hard, dry, bowel movements that

may cause pain or bleeding
 Vinca Alkaloids - Vincristine worst
 Other reasons: dehydration, no activity,
opioid use, low residue diet
 May cause bloating, pain, N&V, obstruction
or ileus, rectal bleeding, hemorrhoids, tears
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
 Stomatitis/Mucositis
 Inflammation or ulceration of mouth which can progress
to entire GI tract
 Destruction of fast-growing epithelial cells
 Drugs: 5-FU, Methotrexate, Xeloda, Bleomycin, HD
chemo
 Radiation fields that include mouth or throat
 Alcohol, tobacco use
 Poor oral hygiene, dental caries
 Causes pain, infection, dehydration, weight loss
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
 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 had prior
to chemo
 MOST distressing symptom
 May be equally distressing for men and women
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 be
insurance benefit--can get script for wig
 Wear headcovering to reduce temperature loss
 Protect scalp from sun (may be photosensitive)
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
Sexual Side Effects

 Related to drug, dose, length of treatment, age and

sex of patient
 Men: impotence, decreased libido, hot flashes,
decreased sperm count, gynecomastia, body image
changes
 Women: irregular or no menses, vaginal dryness,
decreased ova production, painful intercourse,
decreased libido, hot flashes, body image changes
 Management

 Patient education
 Discuss concerns frankly
 Sperm banking
 Birth control
 Lubrications
 Position changes
 Counseling (time of high stress)