Drug Therapy for the Treatment of Cancer

Cancer

Disease process characterized by uncontrolled cell growth, invasiveness and metastasis with numerous etiologies, clinical manifestations, and treatments

Oncology

Study of cancer and its treatment

Purpose of oncologic medication

Kill, damage, or slow growth of cancer cells and prevent/treat adverse effects

Normal cells

• Reproduce in response to the need for tissue growth/repair

• Stop reproduction when the need is met

• Well differentiated in appearance and function

• Have characteristic lifespan

Malignant cells

• Occupy space; serve no useful purpose

• Steal blood and nutrients from normal tissue

• Grow in uncontrolled fashion

• Undifferentiated; loosely connected

• Break off and invade adjacent tissues or circulate throughout the body in bloodstream

Hematologic malignancies

• Invade bone marrow and lymphoid tissue

  • Leukemias, lymphomas, multiple myeloma

Solid neoplasms

• Carcinomas (epithelial tissue)

• Sarcomas (connective tissue)

Malignant Neoplasms: Grading and Staging

• classifications assist in determining treatment modalities.

• Localized tumors:

  • surgery, radiation, or concurrent chemotherapy and radiation

• Metastatic disease:

  • requires systemic chemotherapy alone

Cancer Treatment: Overview

• Surgery

  • Excise localized tumors, treat complications

• Radiation therapy

  • Used alone or in combination

• Chemotherapy

  • Eliminate/control neoplasm growth

  • Relieve symptoms, improve life quality

Chemotherapy- Cytotoxic antineoplastic drugs

• Most standard chemotherapies damage or kill all rapidly dividing normal and cancerous cells.

• Hormone inhibitors (another therapeutic approach) slow the growth of cancer cells stimulated by hormones (breast and prostate cancer).

Goal of treatment w/ cytotoxic antineoplastic drugs

• cure

• remission (period when symptoms of a disease have subsided)

• palliation (alleviation of pain and symptoms)

Antineoplastic Drug Therapy: Overview

• Most regimens involve combination of drugs with differing cellular action.

• Drug resistance is a major problem.

  • Newer drugs used after primary medications become ineffective.

• Usually administered in cycles

  • Taking medications on prescribed schedule with recovery period after each cycle

• Regimens are managed by medical oncologists.

  • Medications administered by specially trained and certified nurses

Oncologic Medication Groups

• Traditional cytotoxic agents

  • alkylating agents, antimetabolites, antibiotics, plant alkaloids

• Biologic targeted therapies (cytotoxic)

  • monoclonal antibodies, growth factor inhibitors

• Hormone inhibitors (non-cytotoxic)

• Medications that reduce adverse effects of cytotoxic medications

Traditional cytotoxic agents

• Alkylating agents

  • cyclophosphamide (Cytoxan)

• Antimetabolites

  • methotrexate (Otrexup)

• Antitumor antibiotics

  • Daunorubicin (Cerubidine)

  • Bleomycin (Blenoxane)

• Plant alkaloids

  • vincristine sulfate (Vincasar, Oncovin)

Safety Precautions With Cytotoxic Antineoplastic Medications

• Most are carcinogenic, mutagenic, and teratogenic.

  • Avoid exposure while pregnant.

• Parenteral solutions are irritating to skin, mucous membranes—avoid direct contact with skin or respiratory tract; wash hands thoroughly after administration.

• do not administer injectable medications unless certified.

Alkylating Drugs

• include nitrogen mustard derivatives, nitrosoureas, platinum compounds, and triazenes.

• Before these drugs are administered, it is important to assess liver function.

Nitrogen Mustard Derivatives (cyclophosphamide) Pharmacodynamics/ Action

prevents cell division through the cross-linking of DNA strands, resulting in decreased DNA synthesis

Nitrogen Mustard Derivatives (cyclophosphamide) Uses/ Indications

neoplasms - including multiple myeloma, sarcoma, & breast cancer

Nitrogen Mustard Derivatives (cyclophosphamide) Contraindications

• Caution with use of aminoglycosides with nephrotoxic agents

• Caution acetaminophen with agents that can cause liver failure

• Caution with use of loop diuretics (furosemide) with agents that may cause hearing loss

Nitrogen Mustard Derivatives (cyclophosphamide) Adverse Effects

• Bone marrow depression

• nausea/vomiting, alopecia

• hemorrhagic cystitis*

• secondary leukemia or bladder cancer

Nitrosoureas (carmustine) Pharmacodynamics/ Action

prevents cell division through the cross-linking of DNA strands, resulting in decreased DNA synthesis

Nitrosoureas (carmustine) Uses/ Indications

• malignant glioblastomas

• hodgkin’s and non-hodgkin lymphomas

• pancreatic islet cell tumors

Nitrosoureas (carmustine) Contraindications

• Caution with use of aminoglycosides with nephrotoxic agents

• Caution acetaminophen with agents that can cause liver failure

• Caution with use of loop diuretics (furosemide) with agents that may cause hearing loss

Nitrosoureas (carmustine) Adverse Effects

• Alopecia

• Anemia, neutropenia, bone marrow suppression, thrombocytopenia

• nausea/vomiting

• Bleeding

• Fatigue

• mucositis

Platinum compounds (carboplatin) Pharmacodynamics/ Action

prevents cell division through the cross-linking of DNA strands, resulting in decreased DNA synthesis

Platinum compounds (carboplatin) Uses/ Indications

cancers of ovaries, head, and neck

Platinum compounds (carboplatin) Contraindications

• Caution with use of aminoglycosides with nephrotoxic agents

• Caution acetaminophen with agents that can cause liver failure

• Caution with use of loop diuretics (furosemide) with agents that may cause hearing loss

Platinum compounds (carboplatin) Adverse Effects

• Alopecia

• Anemia, neutropenia, bone marrow suppression, thrombocytopenia

• nausea/vomiting

• Bleeding

• Fatigue

• mucositis

Triazene compounds (dacarbazine) Pharmacodynamics/ Action

prevents cell division through the cross-linking of DNA strands, resulting in decreased DNA synthesis

Triazene compounds (dacarbazine) Uses/ Indications

• cancers of the lymph system

• malignant melanoma

Triazene compounds (dacarbazine) Contraindications

• Caution with use of aminoglycosides with nephrotoxic agents

• Caution acetaminophen with agents that can cause liver failure

• Caution with use of loop diuretics (furosemide) with agents that may cause hearing loss

Triazene compounds (dacarbazine) Adverse Effects

• Alopecia

• Anemia, neutropenia, bone marrow suppression, thrombocytopenia

• nausea/vomiting

• Bleeding

• Fatigue

• mucositis

Antimetabolites

• Similar to metabolites or nutrients needed by cells for reproduction

• Include:

  • Folate Antagonists

  • Purine antagonists

  • Pyrimidine analogs

Folate antagonist (methotrexate) Pharmacodynamics/ Action

• Inhibits formation of folate

• Interfere with DNA synthesis, repair, and cellular replication

Folate antagonist (methotrexate) Uses/ Indications

• Cancer

• Rheumatoid arthritis, psoriasis, Chron’s Disease

Folate antagonist (methotrexate) Contraindications

Avoid salicylates, NSAIDs, and PPIs

Folate antagonist (methotrexate) Adverse Effects

• Alopecia

• Anemia, neutropenia, bone marrow suppression, thrombocytopenia

• nausea/vomiting

• Bleeding

• Fatigue

• mucositis

Purine antagonist (mercaptopurine) Pharmacodynamics/ Action

Inhibits DNA and RNA synthesis

Purine antagonist (mercaptopurine) Uses/ Indications

Primarily used in leukemias

Purine antagonist (mercaptopurine) Contraindications

severe liver or kidney disease

Purine antagonist (mercaptopurine) Adverse Effects

• Alopecia

• Anemia, neutropenia, bone marrow suppression, thrombocytopenia

• nausea/vomiting

• Bleeding

• Fatigue

• mucositis

Pyrimidine antagonist (fluorouracil – 5FU) Pharmacodynamics/ Action

• Affects DNA and RNA synthesis

• Replaces uracil in tumor cell RNA

Pyrimidine antagonist (fluorouracil – 5FU) Uses/ Indications

Carcinomas, solar keratosis and basal cell carcinoma

Pyrimidine antagonist (fluorouracil – 5FU) Contraindications

severe liver or kidney disease

Pyrimidine antagonist (fluorouracil – 5FU) Adverse Effects

• Alopecia

• Anemia, neutropenia, bone marrow suppression, thrombocytopenia

• nausea/vomiting

• Bleeding

• Fatigue

• mucositis

Plant Alkaloids

• Camptothecins- inhibit enzyme required for DNA replication

• Podophyllotoxins, etoposide and teniposide- cause DNA strand breakage and prevent mitosis

• Taxanes- stop the cell cycle

• Vinca Alkaloids

Plant alkaloids (anti-mitotics) - Camptothecin

• Irinotecan (Camptosar) – used in colon/SCLC

• Topotecan (Hycamtin) – used in ovarian/cervical/SCLC

Plant alkaloids (anti-mitotics) - Podophyllotoxins

• Etoposide (Toposar) – used in lung/testicular/SCLC

• Tenoposide (Vumon) – used in childhood ALL

Plant alkaloids (anti-mitotics) - Taxanes

• Paclitaxel (Taxol, Abraxane) – peripheral neuropathy, >Cr, cardiac effects

• Docetaxel (Taxotere) – peripheral neuropathy

• Carbazitaxel (Jevtana) – febrile neutropenia, >liver enzy

Plant alkaloids- Vinca Alkaloid (vincristine) Pharmacodynamics/ Action

• Cell cycle specific agents

• Interfere with cell mitosis

Plant alkaloids- Vinca Alkaloid (vincristine) Uses/ Indications

Used to treat solid tumors/sarcoma, e.g., Wilm’s tumor

Plant alkaloids- Vinca Alkaloid (vincristine) Contraindications

• Only recommended to be administered IV, deaths have occurred when given intrathecally

• Radiation may be contraindicated

Plant alkaloids- Vinca Alkaloid (vincristine) Adverse Effects

• AVOID EXTRAVASATION AS IT ACTS AS A VESICANT – can cause tissue blistering and necrosis

• severe autonomic nerve injury, e.g. constipation, urinary hesitance, peripheral neuropathy (weakness, numbness, tingling, foot drop, ataxia, & paresthesia) decreased reflexes, sensory loss

Precautions- Preventing Interactions

• Changes in hepatic metabolism most common reason for cytotoxic drug interactions

• Azole antifungals, erythromycin and protease inhibitors increase blood levels of cytotoxic drug

• Carbamezepine, griseofulvin, phenytoin and St. John’s wort can decrease blood levels

Nursing Considerations with Chemo

• Since chemo is administered in cycles, the optimal route for chemotherapy administration is via central venous catheter.

• Several drugs (called vesicants) cause severe inflammation, pain, ulceration, and tissue necrosis if they leak into soft tissues around veins.

• Efforts are needed to prevent extravasation or to minimize tissue damage if it occurs.

Biologic Response Modifiers

• Target differences between malignant and normal cells

• Increases immune response and decreases production of cancer cells

• Useful alone and in combination with cytotoxic drugs

• Includes immunotherapy drugs and drugs that target biologic processes of malignant cells

Newer cytotoxic “biologic targeted therapies”

• Monoclonal antibodies

• Kinase/Growth Factor Inhibitors

• Proteosome Inhibitors

Monoclonal Antibodies (alemtuzumab) Pharmacodynamics/ Action

• Bind to an antigen on T and B lymphocytes and malignant lymphoid cells

• Activate antibody and compliment activated cytotoxicity

Monoclonal Antibodies (alemtuzumab) Uses/ Indications

• Alone or in combination with cytotoxic antineoplastic drugs

• Treatment of cancer

Monoclonal Antibodies (alemtuzumab) Contraindications

• Vary few drug interactions

• Must be given IV- destroyed by GI enzymes if taken orally

Monoclonal Antibodies (alemtuzumab) Adverse Effects

• Heart failure

• Bleeding problems

• Electrolyte imbalances

Targeted MAB - Rituximab (Rituxan)

• MOA – CD20 directed antibodies

• Used to treat non-Hodgkin’s lymphoma, CLL

• Adverse reactions – infusion reactions, rash, hypotension, wheezing; premedicate with antihistamine and/or corticosteroid

  • Treat adverse rxn – stop infusion, administer epinephrine

• Others – flu-like reaction

• Can cause tumor lysis syndrome due to rapid cell death

Kinase Inhibitors - Erlotinib (Tarceva)

• oral

• Adverse effects – increased AST/ALT in this class

Kinase Inhibitors - Imatinib (Gleevec)

• oral

• Adverse effects – flu like symptoms, hypokalemia

Kinase Inhibitors - Ponatinib (Iclusig)

• oral

• Adverse effects – monitor for evidence of arterial occlusion, heart failure, hepatotoxicity, and venous thromboembolism

Antineoplastic Hormone Inhibitor Drugs

• Malignant tumors of the breast, uterus, ovary, and prostate are influenced by hormones.

• Sex hormones act as growth factors in some malignancies. For example, some breast tumors have estrogen receptors, whereas prostate cancer in men grows under stimulation by testosterone.

• Hormone inhibitors slow the growth of cancer cells stimulated by hormones.

Classes of non-cytotoxic agents

• Corticosteroids

  • Suppress lymphocyte production causing lymphocyte apoptosis and regression of lymphoid tissue; other uses include treatment of nausea/vomiting, intracerebral edema, and hypercalcemia

• Anti-estrogens

  • Aromatase inhibitors

• Anti-androgens

  • Gonadotropin releasing hormone agonists

Tamoxifen (Nolvadex)

• Anti-estrogens

• Treatment of breast cancer, stops growth of estrogen dependent cells

• Can be used to treat or prevent breast cancer

• Not cytotoxic

Tamoxifen (Nolvadex) adverse effects

increased tumor or bone pain, hypercalcemia, hot flashes, nausea, fatigue, mood swings, depression, H/A, thinning hair, constipation, dry skin, loss of libido, vaginal discharge/bleeding

Tamoxifen (Nolvadex) possible side effects

endometrial cancer, thromboembolism (DVT, PE, stroke)

Anastrazole (Arimidex)

• Aromatase Inhibitors

• Stops growth of breast cancer cells by blocking estrogen production

Anastrazole (Arimidex) adverse effects

nausea, hot flashes, edema, muscle and joint pain, vaginal bleeding, increased risk of osteoporosis (bisphosphonate can be used to prevent/treat)

Flutamide (Eulexin)

• Anti-androgens

• Blocks testosterone at receptor site

• Used in conjunction with gonadotropin releasing hormone agonist (leuprolide) to block androgen receptors and suppress growth of prostate cancer

• Androgen receptor blockers are used during first weeks of therapy to prevent leuprolide (Lupron) induced tumor flare.

Flutamide (Eulexin) Adverse effects

nausea/vomiting, hot flashes, hepatotoxicity, decreased libido, erectile dysfunction, gynecomastia, decreased bone density, dysrhythmias, pulmonary edema

Leuprolide (Lupron)

• GRHA – Gonadotropin releasing hormone agonist

• Prevents release of lutenizing and follicle stimulating hormones (FSH) to prevent testosterone production by the testicles and estrogen by the ovaries (treating endometriosis)

• Used to treat prostate cancer

Leuprolide (Lupron) adverse effects

nausea/vomiting, hot flashes, hepatotoxicity, decreased libido, erectile dysfunction, gynecomastia, decreased bone density, dysrhythmias, pulmonary edema

Leuprolide (Lupron) nursing considerations

Monitor PSA, testosterone levels, increase Ca++ and vitamin D intake

Cyclophosphamide nursing concerns

administer on empty stomach. If severe stomach upset occurs, give with food. Have Pt. 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.

Doxorubicin nursing concerns

urine may turn red for 1 to 2 days after drug administration. Report edema, shortness of breath, and excessive fatigue. Drug may need to be stopped.

Fluorouracil (5-FU) nursing concerns

increase fluid intake while taking. Common side effects: mucocitis, loss of appetite, hair loss, and inflammation of the skin.

Methotrexate nursing concerns

advise patient to avoid alcohol, ASA, and prolonged exposure to sunlight.

Oxaliplatin nursing concerns

advise Pt. to avoid exposure to cold during & x3 to 5 days post drug administration to prevent or minimize nerve damage (numbness, tingling, and pain in the throat or hands).

Vincristine nursing concerns

promote high-fiber foods to prevent constipation. Maintain a high fluid intake. A stool softener or bulk laxative may be prescribed for daily use

Common Adverse Effects of Traditional Cytotoxic Antineoplastic Drugs

• Infection

• Neutropenia, thrombocytopenia, myleosuppression

• Alopecia, anemia, bleeding

• Fatigue, mucositis

• N/V, Anorexia

• May damage

• Heart

• Liver, kidneys

• Nerves

Tumor Lysis Syndrome

• Most often seen with tx of leukemias and lymphomas

• Can lead to kidney failure, hypocalcemia, hyperkalemia, hyperphosphatemia, hypomagnesemia, hyperuricemia and acidosis.

Tumor Lysis Syndrome Nursing actions

Monitor kidney function (output, BUN, Creatinine and other lab values) and administer dialysis if needed. Monitor for metabolic changes (GI upset, fatigue, altered mental status, hypertension, muscle cramps, paresthesias (numbness & tingling), tetany, seizures, dysrhythmias, cardiac arrest, reduced urine output and acute renal failure).

Tumor Lysis Syndrome prevention or minimization

• Aggressive hydration with NS, alkalinization with IV sodium bicarbonate, and administration of allopurinol to reduce uric acid levels as necessary.

• tx of hyperkalemia with IV dextrose and regular insulin (drive potassium into cells) or Kayexalate to eliminate potassium in the feces.

• tx of hyperphosphatemia with adm. of aluminum hydroxide or other phosphate binder.

• Maintain urine pH of 7 or higher prevents renal failure due to uric acid crystals in the urine.

• Hemodialysis if other measures are ineffective in maintaining urinary elimination

Safety Precautions for Nurses

• Because of the toxicity of these drugs, nurses who administer intravenous (IV) cytotoxic chemotherapy receive special training and are certified in handling and administering the chemotherapy drugs safely and accurately.

• it is also important for the RN to wear protective equipment when preparing chemotherapy infusions to protect from harm from the toxic nature of the drugs.

• Several drugs (called vesicants) cause severe inflammation, pain, ulceration, and tissue necrosis if they leak into soft tissues around veins. Thus, efforts are needed to prevent extravasation or to minimize tissue damage if it occurs. That’s why most patients have an implanted port for chemo infusions

Safety Precautions With Cytotoxic Antineoplastic Medications

• Most are carcinogenic, mutagenic, and teratogenic.

  • Avoid exposure while pregnant.

• Parenteral solutions are irritating to skin, mucous membranes—avoid direct contact with skin or respiratory tract; wash hands thoroughly after administration.

• do not administer injectable medications unless certified.

Chemotherapy handling and spills

• Follow institutional procedures

• Small spills can be handled with a spill kit

  • Goggles, mask, protective clothing, shoe covers, absorbent pads, detergent cleaners, chemotherapy waste disposal bags

• Large spills – contact hospital safety department