Cancer chemotherapy

NRS 308
Module 7

Cancer cells
Characterized by
persistent proliferation
invasive growth
and the ability to form metastases (spread elsewhere in
the body)

May be treated 3 ways:

Surgery
Radiation
Chemotherapy

Chemotherapy
3 major classes:
Cytoxic agents (drugs that kill cells directly)
Hormones and hormone antagonists
Biologic response modifiers (gets the bodys immune
system to attack the cancer directly)

Toxicity to normal cells is the #1 barrier to success

in chemotherapy
Especially in tissues that divide rapidly
Bone marrow, GI tract, hair, testes also divide
rapidly and thus tend to have significant adverse
effects

Selective toxicity
Chemo drugs lack selective toxicity
Makes them harmful to normal tissues as well as cancer
cells

Chemo drugs cannot kill target cells without also

killing other cells with which the target cells are in
intimate contact
Cancer cells and normal cells are very similar
chemo drugs cannot tell them apart
Chemotherapy drugs work best against cancer
cells that are rapidly dividing

No help from the body, either

In contrast to antibiotics, chemo drugs receive
minimal help from the bodys own defense system
in killing the cancer cells
Chemo drugs suppress bodys immune system
Immune system generally fails to recognize cancer cells
as appropriate for attack

Chemo drugs must work entirely on their own to kill

the cancer cells

Drug resistanceits not just for antibiotics!

During course of chemotherapy, cancer cells can
develop resistance to the drugs used against them
Usually results from change in cancer cells DNA
Because resistant cells cannot be killed with drugs,
the risk of therapeutic failure becomes greater
with each round of treatment

Other challenges for chemo

drugs
Tumors may consist of a variety of cancer cells
Tumor cells mutate constantly, and become groups of
dissimilar cells
Can differ in responsiveness to chemo drugs, with
varied levels of resistance

Some tumors have limited blood supply, so chemo

drugs have limited access to the cancer cells
Tumors within the CNS are hard to reach because
of the blood-brain barrier

Intermittent chemo
Chemo usually administered intermittently
Normal cells have time to repopulate between
rounds of chemo
Normal cells must then repopulate faster than
cancer cells!
If cancer cells grow faster than the normal cells,
will see no reduction in tumor mass

Combination chemo
Suppresses drug resistance
chance of mutating to survive multiple drugs

Increases cancer cell kill

Kill more cancer cells when use multiple drugs
with different mechanisms of action

Reduces injury to normal cells

Can use lower doses and reduce toxicity to
normal cells

Bone marrow suppression

Chemo is highly toxic to bone marrow
# of white blood cells (WBC)
risk of infection
ability to fight off infections

# of red blood cells (RBC)

Anemia

# of platelets (PLT)
Bleeding, inability to clot

Neutropenia
Infection secondary to WBC is the most serious
complication of chemo
Onset is usually rapid and recovery develops
quickly
Begins few days after dosing, reaches lowest point
(nadir) at days 10-14, recovers in 3-4 weeks

Some drugs delayed neutropenia

Fall in 1-2 weeks, nadir between weeks 3& 4, recover
after week 7

If WBC <500, chemo should be held until WBC

back to normal

Colony Stimulating Factors

Some drugs can stimulate production of
cells within the bone marrow
Neumega increase platelets
Neupogen, Procrit increase red blood cells
Leukine increase white blood cells

Very expensive (may be thousands of $ per

dose)
Usually given by injection

Thrombocytopenia
Reduction in circulating platelets
Drugs that promote bleeding should be
avoided (ASA, Motrin, coumadin)
Patients should take Tylenol as needed for
minor aches
Caution with venipuncture, brushing teeth,
shaving, IM injections

Anemia
Anemia is usually less severe than
neutropenia and thrombocytopenia
RBCs have longer lifespan, so can recover
before levels of existing RBCs falls too low

Erythropoietin helps RBC levels and

avoid transfusions
Cannot be used in patients with leukemia or
multiple myeloma

GI tract injury
Chemo can cause stomatitis (inflammation
of the oral mucosa)

Starts few days after chemo

May persist for weeks after chemo completed
May lead to ulceration and severe pain
May develop yeast infection (thrush)
May leave patient unable to eat

Nausea & vomiting

Much more severe than with other drugs
Result from direct stimulation of the nausea
& vomiting chemoreceptors in the brai
Can be reduced by pre-medicating with
combination of antiemetic drugs
Decadron, Emend
Zofran, Ativan, Compazine

Alopecia
Reversible hair loss results from injury to hair
follicles
Can occur with most cytotoxic chemo drugs
Begins 7-10 days after treatment started
Maximal 1-2 months
Regeneration 1-2 months after treatment ended

Second only to nausea as greatest treatmentrelated fear

Hair may come back with different appearance
than before chemo
Different color, may become curlier or straighter

Handling of chemo drugs

Certain chemo drugs can cause severe injury if
touch skin or tissues directly
Gloves should always be worn when handling chemo
drugs
Gown and goggles are sometimes appropriate

Always given IV because rapid dilution in blood

minimizes risk of injury to tissues
Usually given through a central IV line directly into
superior vena cava rather than IV in the arm
If leakage of chemo drug occurs at IV site, may cause
severe ulceration resulting in pain, infection and
necrosis

Reproductive toxicity
Testes
Chemo drugs can severely injure germinal epithelium
in the testes (where sperm are manufactured)
Can cause irreversible sterility sperm banking may
be recommended

Developing fetus
Can cause death of early embryo or severe fetal
malformation
Women undergoing chemo should be warned against
becoming pregnant

Cytotoxic drugs
Act directly on cancer cells to cause their death
Are also toxic to normal body tissues
Characteristics:
Mutagenic: causes changes in cellular DNA
Teratogenic: causes birth defects
Carcinogenic: can cause new cancer

Healthcare personnel must follow safe handling

procedures!
Gown/gloves/goggles
Approved techniques for administration

More toxic to cells that are actively dividing

Examples of cytotoxic chemo drugs

Cytoxan (cyclophosphamide): active against
wide variety of cancer cells
BCNU (carmustine): can be administered as
a wafer inserted into brain tissues to treat
cancer within the CNS
Platinol (cisplatin): high rate of nausea &
vomiting (may last for days)

Examples of cytotoxic chemo drugs

Oncovin (vincristine): may cause severe
peripheral nerve damage but little bone marrow
suppression
Taxol (paclitaxel): may cause severe
hypersensitivity reactions and severe bone marrow
suppression
Adriamycin (doxorubicin): may cause severe heart
damage

Nolvadex (tamoxifen)
Most widely prescribed drug for breast cancer
Drug of first choice for treating breast cancer
Blocks estrogen receptors on breast cancer cells
Estrogen acts on tumor cells to stimulate growth and
proliferation
Absence of estrogen tumor cell proliferation
decreases
Target cells must be estrogen receptor (ER) positive

Uses for Nolvadex

1. Adjunct therapy to suppress of residual cancer
cells following total mastectomy, lumpectomy,
and breast irradiation

Benefits limited to women with ER-positive cancer

cells

2. Treatment of breast cancer that has metastasized

3. Also approved for reducing risk of breast cancer
development in healthy women at high risk

Reduces incidence by 44%

Risks: increased chances of endometrial CA, PE and
DVT
Only for women at high risk of developing breast CA

Nolvadex adverse effects

Hot flashes, vaginal discharge, fluid retention
Biggest concern:
Increased risk of developing endometrial cancer
Acts as an estrogen agonist at receptors in the uterus
Causes proliferation of endometrial tissue
endometrial hyperplasia (overgrowth of tissue) may
lead to endometrial CA

Biologic response modifiers

Drugs that alter host responses to cancer
Effects:
Stimulate the immune system
Render cancer cells nonmalignant
Help body better tolerate bone marrow suppression
caused by other chemo drugs

Interferon enhances immune response to cancer

cells and help keep cancer cells from dividing

Targeted drugs
Targeted anticancer drugs bind with specific
molecules (targets) on cancer cells that drive tumor
growth
Are more selective than hormones
Kill cancer cells without harming bodys cells

Gleevec: inhibits enzyme unique to leukemia cells

Herceptin: antibody used for breast CA cells that
are HER2-positive