Cancer chemotherapy

NRS 308Module 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 body’s 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 body’s own defense system in killing the cancer cells

– Chemo drugs suppress body’s 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 resistance- it’s 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 cell’s 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 treatment-related 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 Nolvadex1. 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 body’s cells

• Gleevec: inhibits enzyme unique to leukemia cells

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