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 Burkitts 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
Inhibits adenosine synthesis synthesis
Deaminase Inhibits Pyrimidine
Biosynthesis

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

METHOTREXATE 5-FLOUROURACIL
Inhibit dihydrofolate
reduction, blocks Inhibit TMP
TMP and Purine Synthesis
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
PROTEINS COLCHICINE
asparagine
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: Hodgkins 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 (Hodgkins and non-Hodgkins),
Neuroblastoma
Kaposis 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-HT 3
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)