Chemotherapy Drugs Revised

Genes that normally function to restrain cell growth. However, they can become defective and lose ability to inhibit cell growth/division → allows cancer formation.

Tumor suppressor genes

Ex of tumor suppressor gene

p53 gene is a tumor suppressor gene in cells that controls cellular apoptosis (natural death of cells with damaged DNA). Defect of this gene can lead to cancer formation

Genes that stimulate and regulates a cell’s movement through the cell cycle, resulting in cellular growth and proliferation

Proto-oncogenes/oncogenes

What happens when proto-oncogenes become mutated?

These proto-oncogenes genes become oncogenes that stimulate constant, unrelenting proliferation and cell cycling.

Cancer treatment that involves short course of high-dose drug therapy after radiation, OR surgery to destroy residual cancer cells to prevent recurrence. Or drugs used to kill any residual cancer cells after surgery.

Adjuvant treatment

Cancer treatment done prior to surgery. Radiation to shrink tumor and improve outcomes.

Neoadjuvant treatment

Cancer treatment to control symptoms, comfort, improve QOL if cure not available.

Palliative treatment

Cancer treatment involving potentially curative high dose for recurrence or treatment failure.

Salvage treatment

Why is cancer/chemo treatment intermittent?

So normal cells can replenish while maximizing killing of cancer cells

• Reduces drug resistance

• Increase cancer kill count

• Reduces injury to normal cells

Combination therapy

Why does combination therapy reduce drug resistance of cancer cells?

Multiple drugs with different MOAs overwhelm cancer cells so that cancer cells do not have time to adapt resistance to just one drug; combination therapy is also more likely to kill cancer cells. Some meds also protect normal cells from other chemo drugs → give concurrently

Regional drug therapy

Chemotherapy can target specific spots of the body depending on where they are administered

Cell-cycle phase-specific drugs (cytotoxic agents) MOA

• Toxic only to cells in a particular phase

• Cells in G0 phase are not harmed

• Schedule dependent

Cells in G0 phase are harmed/attacked by cell-cycle phase-specific cytotoxic agents. True or false?

False

Phase non-specific drugs (cytotoxic agents) MOA

• Acts during any phase, including G0

• More toxic to proliferating cells than cells in G0

Safe handling of cytotoxic agents

• Protect yourself from exposure

• Don appropriate PPE (gown, gloves, mask, face shield/goggles, shoe covers)

• Follow institutional guidelines

Nursing implications for cytotoxic agents

• High-alert medication

• 2 nurse check with several additional “Rights”

• BSA/Weight based dosing (mostly use BSA-dosing; body surface area)

• Monitor/double check administration rate 

Cell-cycle phase-specific drugs vs phase non-specific drugs

• Phase non-specific acts during any phase, including G0 (cell-cycle phase-specific does NOT act on G0)

• Phase non-specific drugs are more toxic to proliferating than cells in G0

Safe IV administration cytotoxic agents

• Central line vs peripheral IV access (most cytotoxic agents/chemo drugs are given IV central line)

• Cytotoxic agents are an irritant (causes extravasation/phlebitis) → usually occurs peripheral IV

• Vesicant (term given to drug that can cause tissue necrosis or damage if it leaks outside the vein and enters tissue (can lead to permanent destruction, nerve damage, limb loss)

• Hourly IV checks and documentation

• Vesicants best given central line to not worry about extravasation

Term given to drug that can cause tissue necrosis or damage if it leaks outside the vein and enters tissue (can lead to permanent destruction, nerve damage, limb loss; caused by cytotoxic agents. 

Vesicant

Vesicants (e.g. cytotoxic agents) are best given central or peripheral line to not worry about extravasation or irritation?

Central line

It is important to note that the vast majority of chemotherapeutic drugs are administered by a ______ line indwelling catheter device to minimize the risk for extravasation.

Central line

S&S of IV infiltration of tissue

• Redness at or near the insertion site with swollen, taut skin with pain

• Blanching, and coolness of skin around the IV site

• Slowed or stopped IV infusion

• No blood return obtained

Treating extravasation/irritant/vesicant

• Notify provider

• Administer antidote to prevent damage from leakage of drug into tissues

• Follow hospital policy

• Central line vs peripheral IV access (most cytotoxic agents/chemo drugs are given IV central line)

• Cytotoxic agents are an irritant (causes extravasation/phlebitis) → usually occurs peripheral IV

• Vesicant (term given to drug that can cause tissue necrosis or damage if it leaks outside the vein and enters tissue (can lead to permanent destruction, nerve damage, limb loss)

• Hourly IV checks and documentation

• Vesicants best given central line to not worry about extravasation

Safe IV administration cytotoxic agents

Preventing IV extravasation from cytotoxic agents

• Follow hospital policy/protocol

• Check for blood return in IV prior to administering chemo

• Assess patient for pain, burning regularly

• Stop drug immediately if signs of infiltration are noted

  • Give antidote through existing IV if extravasation happens

• Aspiration of drug (5 mL blood) prior to IV removal

• Elevate extremity

• Warm compress/cold compress

  • Determined by specific chemo drug

Types of cytotoxic drug classifications based on MOA

• MOA

  • Cell-cycle phase-specific drugs

  • Phase non-specific drugs

Types of cytotoxic agents

• Alkylating agents

• Platinum compounds

• Antimetabolites

• Antitumor abx

• Mitotic inhibitors

• Other classes

Alkylating agents (cyclophosphamide (Cytoxan, Neosar))

• Cell cycle-nonspecific

• Alkyl groups are part of the alkylating drugs’ structure that attach to DNA molecules by forming covalent bonds.

• As a result, abnormal chemical bonds form between the adjacent DNA strands, which leads to the formation of defective nucleic acids that are then unable to perform the normal cellular reproductive functions, which leads to cell death.

• Nitrogen mustard derivative cytotoxic agent transfers alkyl group that disrupts DNA replication → prevents cancer cells from reproducing leading to death.

Alkylating agents (cyclophosphamide) indication

Broad-spectrum chemo drug effective against a myriad of malignancies. 

Among the first antineoplastic drugs developed

Alkylating agents (cyclophosphamide) 

Cyclophosphamides (alkylating agents) AE/SE

• Can cause acute hemorrhagic cystitis

  • Patient needs adequate hydration (2-3 L) to prevent hemorrhagic cystitis

  • Concurrent mesna (Mesnex) for high dosage to prevent hemorrhagic cystitis

If using high dosage of this drug, administer concurrently mesna (Mesnex); also provide adequate hydration (2-3 L) → both serve to prevent hemorrhagic cystitis

Cyclophosphamides (alkylating agents)

Drug that has AE of hemorrhagic cystitis

Cyclophosphamides (alkylating agents)

Platinum compounds MOA

Contains platinum that cross-links in cell DNA

Name the platinum compounds

Cisplatin (Platinol-AQ)

Platinum compounds indication

• Testicular cancer

• Ovarian

• Bladder cancer

TOB (platinum compounds/cisplatin indication)

• Testicular cancer

• Ovarian cancer

• Bladder cancer

Cytotoxic agent that causes nephrotoxicity & ototoxicity

Cisplastin

Complications of chemo

• Bone toxicity/bone marrow suppression

• GI upset (NV)

• Skin and hair loss (alopecia)

• Sexual dysfunction

• Tumor lysis

• Carcinogenesis; treatment can cause cancer by damaging DNA in normal cells

• Anemia/thrombocytopenia

• Immunosuppression/neutropenia

Preventing nephrotoxicity caused by platinum compounds

Vigorous hydration + diuretic administration

Cisplatin (platinum compound) AE

• Nephrotoxicity & Ototoxicity

• Peripheral neuropathy

Name the antimetabolites

• Methotrexate (Rheumatrex, Trexall)

• Fluorouracil (Adrucil, 5 FU)

Antimetabolites MOA

• Disrupt/antagonize critical metabolic processes for cellular reproduction (e.g. folic acid, purines, pyrimidines); methotrexate antagonizes folic acid.

• Interferes with body’s ability to use nutrients crucial for DNA synthesis.

• Cell cycle specific; works primarily in S phase (phase where DNA synthesis most active)

DNA synthesis is disrupted by these drugs whether or not specific or nonspecific

Cytotoxic agents

Methotrexate AE/SE

• Stomatitis

• Photosensitivity

• High doses (toxic effect/OD) can injure kidneys (nephrotoxicity)

  • maintain hydration & alkaline urine pH

AE of this drug is stomatitis; high doses (toxic effect/OD) can injure kidneys/nephrotoxicity.

Methotrexate

Methotrexate timed levels

Scheduled blood draws to measure methotrexate concentration at set times after a high-dose infusion (e.g., at ~24, 48, and 72 hours).

High-dose methotrexate is associated with severe bone marrow suppression and is always given in conjunction with the “rescue” drug

Leucovorin. Leucovorin is an antidote for folic acid antagonists.

Drug given after/in conjunction w/ methotrexate to rescue healthy cells

Leucovorin 

Fluorouracil (antimetabolite indication)

Used extensively for solid tumors

Fluorouracil AE

Hand-foot syndrome; form of dermatologic toxicity is known as palmar-plantar dysesthesia or paresthesia (also called hand-foot syndrome). It can range from mild symptoms such as painless swelling and erythema to painful blistering of the patient’s palms and soles.

Drug that causes hand-foot syndrome

Fluorouracil (antimetabolite)

Antitumor abx MOA

• Injure cells through direct interaction with DNA

• Intercalation: drug molecule is inserted between the two strands of a DNA molecule, ultimately blocking DNA synthesis.

• These drugs inhibit the enzyme topoisomerase II, which leads to DNA strand breaks. Many of these drugs are able to generate free radicals, which also leads to DNA strand breaks and programmed cell death.

• Only used to treat cancer, not infections

Antitumor abx can treat both infections and cancer. True or false?

False

Name the antitumor abx

• Daunorubicin & doxorubicin

• Bleomycin

Drugs that cause cardiotoxicity due to toxicity/OD

Daunorubicin & doxorubicin

Daunorubicin & doxorubicin (antitumor abx) cardiotoxicity monitoring

Perform ECHO & check LVEF prior to administration

Toxic levels/OD of this antitumor abx causes pulmonary toxicity (pulmonary fibrosis + pneumonitis)

Bleomycin

Antitumor abx indication

Treat a variety of solid tumors and also some hematologic malignancies.

Daunorubicin & doxorubicin AE

• Hepatotoxicity/liver toxicity

• Toxic effect → Cardiotoxicity/HF

• Daunorubicin causes tissue damage if it extravasates 

Mitotic inhibitors MOA

• Interfere with processes during mitosis → retard cell division, inhibit cell division → cell death

• Vinca alkaloid

Name the mitotic inhibitors 

Vincristine

Vincristine (Oncovin) AE/SE

• Peripheral neuropathy

• Never administered intrathecally (into brain/subarachnoid space)

Chemo drug never administer intrathecally

Vincristine (Oncovin; mitotic inhibitor)

• Administer this drug on empty stomach. If severe stomach upset occurs, give with food.

• Have patient  drink 2 - 3 quarts of fluid daily and urinate often, especially at bedtime.

• If hematuria or signs of cystitis, report provider.

• High fluid intake and frequent emptying of the bladder help to decrease bladder damage

Cyclophosphamide specific concerns

Administer this drug on empty stomach. If severe stomach upset occurs, give with food.

Cyclophosphamide

High fluid intake and frequent emptying of the bladder help to decrease bladder damage from this drug 

Cyclophosphamide 

Drug causes urine to turn red for 1-2 days after administration → NORMAL (discoloration harmless; does not indicate bleeding)

Doxorubicin

Report edema, SOB, excessive fatigue for patients taking this drug (due to cardiotoxicity)

Doxorubicin → drug may need to be stopped/held

Drink plenty of fluids while taking

Fluorouracil

Avoid alcohol, aspirin, and prolonged exposure to sunlight with this drug

Methotrexate

Avoid exposure to cold during, and 3-5 days after administration of this drug. 

Oxaliplatin (alkylating drug)

Why avoid cold exposure during and 3-5 days after administration of oxaliplatin?

Helps prevent or minimize nerve damage that may cause numbness, tingling, and pain in the throat or hands.

Swallowing and daily activities that require hand grasping may be impaired if taking this drug

Oxaliplatin

• Eat high-fiber foods such as whole cereal grains, to prevent constipation.

• Also, try to maintain a high fluid intake

• Stool softener or bulk laxative may be described for daily use

Vincristine

Stool softener or bulk laxative may be described for daily use for patients taking this drug

Vincristine

Drugs used for hormonal cancer therapy

• Tamoxifen (more common)

• Anastrozole

• Flutamide

• Leuprolide (more common)

Drugs used for breast cancer

• Tamoxifen

• Anastrozole

Tamoxifen/anastrozole MOA

• Blocks estrogen receptors on breast cancer cells (tamoxifen) 

• Anastrozole reduce available estrogen to cancer cells

Hormonal therapy indication

Breast cancer & prostate cancer

Leuprolide/flutamide MOA

Suppresses androgen production (suppress testosterone; testosterone can drive prostate cancer) OR availability by binding to androgen receptor cells

Drugs used for prostate cancer

Leuprolide (more common) & flutamide

Hormone-receptive negative breast cancer →

Tamoxifen does not work

What chemo drug causes pulmonary fibrosis or pneumonitis as a toxic effect

Bleomycin

Chemo drugs that cause peripheral neuropathy

• Vincristine/Vinblastine

• Cisplatin

Complications of chemotherapy

• Bone marrow suppression → anemia

• GI upset (NV

• Skin & hair loss (alopecia)

• Sexual dysfunction

• Tumor lysis (large amounts of cancer cells released into bloodstream after chemotherapy treatment)

• Carcinogenesis; treatment can cause cancer by damaging DNA in normal cells

• Immunosuppression/neutropenia

GI effects of chemo

• Stomatitis

• Oral thrush

• NVD

• Constipation

Interventions for stomatitis and oral thrush caused by chemotherapy

• Maintain oral hygiene: soft toothbrush, baking soda, mouthwash, assess for infections.

• Educate to not eat tomatoes/acids to avoid irritating ulcers

• Meds: cytoprotective agents, antifungals, local anesthetics (lidocaine), pain meds

Interventions for NV caused by chemotherapy

• Eliminate triggers

• Monitor nutrition/fluid status

• Give antiemetics 30 min to 1 hr before meals

Interventions for diarrhea caused by chemo

• Monitor nutrition/fluid status, skin integrity. 

• Meds → antidiarrheals/probiotics

Labs to monitor for chemotherapy patient

• CBC; WBCs (neutropenia), RBCs (anemia/erythrocytopenia),

• Platelets (thrombocytopenia) → S&S bleeding/bruising/epistaxis, GI bleeding/belly pain (melena, hematochezia)

Interventions for constipation caused by chemo

• Activity level (encourage ambulation), fiber diet, fluids

• Meds → stool softeners, laxatives

Interventions for mucositis caused by chemo

• Use soft toothbrush

• Avoid tart, salty or acidic food

• Eat soft, bland or cool foods

• Avoid alcohol-based mouthwash (give baking soda/lidocaine mouthwash)

• Rinse before and after meals and bedtime

• Use soft toothbrush

• Avoid tart, salty or acidic food

• Eat soft, bland or cool foods

• Avoid alcohol-based mouthwash (give baking soda/lidocaine mouthwash)

• Rinse before and after meals and bedtime

Interventions for mucositis caused by chemo

Skin & hair effects caused by chemo

• Maintain skin integrity

  • Rash, dry, peeling

• Alopecia (loss of hair)

  • Hairpieces

• Body image

  • Consider psychiatric referral

Oncologic medical emergency; when tumor cells lyse and contents release into bloodstream; releases potassium, phosphate, and uric acid; contributes to acidosis.

• More common in leukemia and lymphoma patients; at beginning of treatment.

Tumor lysis syndrome

Electrolyte imbalances caused by tumor lysis syndrome

• hyperkalemia

• hyperphosphatemia

• Hyperuricemia

• Hypomagnesemia

All contribute to metabolic acidosis

Interventions for tumor lysis syndrome

• Vigorous IV hydration (sodium bicarb), monitor I&Os

• Frequent labs – electrolytes, uric acid, WBC, Cr

• ECG/EKG monitoring (hyperkalemia/dysrhythmias and peaked T waves)

• Allopurinol (Zyloprim, Aloprim) prevent gout due to uric acid buildup

• urate oxidase (Rasburicase) prevent gout due to uric acid buildup

• sevelamer (Renagel) → treat hyperphosphatemia

• Dialysis for severe cases

Preventing gout caused by excess buildup of uric acid due to tumor lysis syndrome

Administering allopurinol (Zyloprim, Aloprim) and urate oxidase (Rasburicase) to prevent gout