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Drugs for Cancer Treatment - Chapter 17

CHAPTER 17: Drugs for Cancer Treatment

Page 1

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Page 2: OVERVIEW

  • Cancer overview

  • Traditional chemotherapy

  • Hormone therapy for cancer treatment
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Page 3: OVERVIEW OF CANCER

  • Cancer is a result of abnormal cell growth.

  • Changes to the normal DNA result in damage or alterations in gene expression, leading to:

    • Loss of normal cell growth controls

    • Uncontrolled growth

  • Reference Table 17.1 on Page 333 regarding the characteristics of normal and cancer cells.
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Page 4: CANCER CELL BIOLOGY

  • Mitosis: The process of cell division.

  • Neoplasia: The condition when new or continued abnormal cell growth occurs that is unnecessary for normal development or tissue replacement.

    • Benign tumors: Grow by expansion rather than invasion; do not metastasize.

  • Loss of gene expression processes controlling normal cell growth and function.
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Page 5: CANCER CELLS

  • Cancer cells undergo continuous cell division.

  • They divide more rapidly than normal cells.

  • They possess an unlimited lifespan, overgrow, and can spread (metastasize) through invasion into other body areas.
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Page 6: CANCER DEVELOPMENT

  • Malignant transformation or carcinoma: The multistep process by which a normal cell transforms into a cancer cell.

  • Carcinogens: Substances or events that can damage normal cell DNA and contribute to cancer development.

  • Primary tumor: The original site where a cancerous tumor arises.

  • Metastasis: This occurs when cancer cells migrate from the site of the primary tumor through hematologic or lymphatic spread, establishing tumors in new areas of the body.
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Page 7: The Cell Cycle

  • Cell Cycle Stages:

    • Gā‚ (1st gap phase)

    • S (synthesis phase: DNA replication)

    • Gā‚‚ (2nd gap phase)

    • M (mitotic phase)
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Page 8: CAUSES OF CANCER

Three interacting factors that influence cancer development:

  1. Exposure to carcinogens

  2. Genetic predisposition

  3. Immune function
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Page 9: CAUSES OF CANCER

Personal and Environmental Factors:

  • Environmental carcinogens:

    • Chemicals

    • Physical agents

    • Certain viruses (oncoviruses)

  • Personal factors:

    • Immune function

    • Age

    • Genetic risk
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Page 10: CANCER TREATMENT APPROACHES

Two primary categories:

  1. Local treatment:

    • Surgery & radiation therapy.

    • Most effective for tumors confined to a localized area.

  2. Systemic treatment:

    • Traditional chemotherapy, hormone therapy, biologics, or targeted therapies.

    • Can have a cancer-killing effect throughout the body.

    • Often used in combination to effectively kill cancer cells.
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Page 11: CANCER DRUG NOMENCLATURE

  • Malignant neoplasm: More technical term for cancer.

  • Antineoplastic drugs: Medications used for cancer treatment.

    • Other terms: cancer drugs, anticancer drugs, cytotoxic chemotherapy, or simply chemotherapy.
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Page 12: TRADITIONAL CHEMOTHERAPY

  • Uses cytotoxic drugs aimed at killing cancer cells.

  • These drugs damage cancer cell DNA and interfere with cell division.

  • Categories vary, yet they share the common outcome of limiting cancer cell division, leading to cancer cell death.

  • They damage both normal and cancer cells.

  • Chemotherapeutic agents can be cell-cycle specific or cell-cycle nonspecific.
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Page 13: TRADITIONAL CHEMOTHERAPY CAUTION!

  • Dosage is calculated based on the patientā€™s body surface area (BSA).

  • Monitor the absolute neutrophil count (ANC), which measures neutrophils (critical infection-fighting white blood cells).

    • Normal healthy neutrophil range: 2,500 ā€“ 6,000 cells/mmĀ³.

  • All chemotherapy drugs are classified as high-alert drugs because incorrect dosaging can cause severe harm.

  • Only chemotherapy-certified registered nurses are authorized to administer traditional chemotherapy drugs.
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Page 14: CHEMOTHERAPY TERMS

  • Dose-limiting adverse effects: commonly impact the GI tract and bone marrow.

  • Other terms:

    • Alopecia (hair loss)

    • Emetic potential (vomiting risk)

    • Myelosuppression (bone marrow suppression)

    • Extravasation (leakage into surrounding tissues)

    • Targeted drug therapy.
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Page 15: CATEGORIES OF CHEMOTHERAPY DRUGS

  • Types of drugs include:

    • Alkylating agents

    • Antimetabolites

    • Antitumor antibiotics

    • Topoisomerase inhibitors

    • Mitotic inhibitors (also known as antimitotic agents)

    • Combination therapy (using more than one class).
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Page 16: CHEMOTHERAPY DRUGS

Considerations include:

  1. Action (how the drug works)

  2. Uses (types of cancer treated)

  3. Expected Side Effects

  4. Adverse Reactions

  5. Nursing Implications and Patient Teaching
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Page 17: ALKYLATING AGENTS

  • Action:

    • Prevent cell division by damaging DNA.

  • Uses:

    • Effective against lung, breast, and ovarian cancers, as well as leukemia, lymphoma, Hodgkin's disease, multiple myeloma, and sarcoma.

  • Expected Side Effects:

    • Nausea, vomiting, alopecia.

  • Adverse Reactions:

    • Bone marrow toxicity, suppression of granulocytes and platelets, GI toxicities, pulmonary damage and fibrosis, renal toxicity.

  • Nursing consideration: Report bruising, petechiae, or ecchymosis related to low platelet counts.
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Page 18: Alkylating Agents Overview

List of Alkylating Agents (Table 17.2):

  • altretamine

  • ifosfamide

  • bendamustine

  • lomustine

  • busulfan

  • mechlorethamine

  • carboplatin

  • melphalan

  • carmustine

  • chlorambucil

  • cisplatin

  • cyclophosphamide

  • oxaliplatin

  • temozolomide

  • thiotepa

  • trabectedin

  • dacarbazine
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Page 19: ALKYLATING AGENTS EXAMPLES

  • Cisplatin (Platinol):

    • Used for solid tumors.

  • Cyclophosphamide (Cytoxan):

    • Treats bone, lymph, blood, and solid tumors.

  • Mechlorethamine (Mustargen, nitrogen mustard):

    • Used for Hodgkin's lymphoma.

  • Others include various alkylating agents discussed previously.
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Page 20: ANTIMETABOLITES

  • Action:

    • Considered cell-cycle-specific drugs as they interfere with DNA synthesis.

  • Uses:

    • Effective against leukemias and cancers of the breast, ovary, head and neck, and gastrointestinal (GI) system, including colon, rectal, breast, stomach, lung, pancreatic cancers.

    • Should not be used in pregnancy or breast-feeding due to teratogenic effects.
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Page 21: ANTIMETABOLITES INDICATIONS

  • Used in combination with other drugs to treat various cancer types.

  • Can be administered in oral and topical forms for low-dose maintenance and palliative therapy.

  • Methotrexate is also used for severe psoriasis and rheumatoid arthritis.
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Page 22: ANTIMETABOLITES ADVERSE EFFECTS

Expected Side Effects:

  • Nausea, vomiting, loss of appetite, diarrhea, constipation, fatigue, headaches, alopecia.

Adverse Reactions:

  • Liver damage (hepatotoxicity), bone marrow suppression, severe GI effects, and neurological, cardiovascular, pulmonary, genitourinary, dermatological, ocular, optic, and metabolic toxicity.

  • Tumor lysis syndrome.

  • Stevens-Johnson syndrome, toxic epidermal necrolysis.
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Page 23: Tumor Lysis Syndrome

Risk Factors:

  • Large tumor burden.

  • Marked increase in lactate dehydrogenase (LDH).

  • Pre-existing chronic kidney disease/acute kidney injury (CKD/AKI).

Laboratory Diagnosis Criteria:

  • At least two abnormalities within 24 hours, for example:

    • Phosphorus: ā‰„4.5 mg/dL

    • Potassium increase of 25% or ā‰„6 mEq/L

    • Corrected Calcium: increase 21.5 ULN

    • Uric acid increase of 25% or ā‰„8 mg/dL

Clinical Diagnosis Criteria:

  • At least one clinical criterion indicating symptoms such as arrhythmia or seizure.

Management:

  • Maintain high urine flow, aggressive intravenous hydration, manage electrolyte abnormalities, consider uric acid therapy (allopurinol or rasburicase), and hemodialysis for refractory hyperkalemia or symptomatic hypocalcemia.

  • Tumor lysis syndrome is an oncologic emergency characterized by metabolic abnormalities that can lead to severe complications.
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Page 24: Table 17.3 Antimetabolites

  • azacitidine

  • gemcitabine

  • capecitabine

  • hydroxyurea

  • cladribine

  • clofarabine

  • 6-mercaptopurine

  • methotrexate

  • cytarabine

  • nelarabine

  • decitabine

  • pemetrexed

  • 5-fluorouracil

  • pentostatin

  • floxuridine

  • fludarabine

  • pralatrexate

  • thioguanine
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Page 25: ANTIMETABOLITES CONTINUED

Categories Include:

  1. Folate (folic acid) antagonists:

    • Interferes with the use of folic acid, preventing DNA production, leading to cell death.

  2. Purine antagonists:

    • Interrupt metabolic pathways of purine nucleotides, disrupting DNA and RNA synthesis.

  3. Pyrimidine antagonists:

    • Interrupt metabolic pathways of pyrimidine bases, also leading to the inhibition of DNA and RNA synthesis.
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Page 26: ANTIMETABOLITES EXAMPLES

  • Folate antagonists:

    • Methotrexate (MTX), pemetrexed, pralatrexate.

  • Purine antagonists:

    • Fludarabine (F-AMP), mercaptopurine (6-MP), thioguanine (6-TG), cladribine, pentostatin.

  • Pyrimidine antagonists:

    • Fluoracil (5-FU), cytarabine (ara-C), capecitabine, floxuridine (FUDR), gemcitabine.
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Page 27: ANTITUMOR (CYTOTOXIC) ANTIBIOTICS OVERVIEW

  • These are cell-cycle nonspecific and act by binding with DNA to prevent necessary RNA synthesis for cell survival.

  • Divided into two subcategories:

    1. Anthracycline antibiotics

    2. Nonanthracycline antibiotics

  • Adverse Effect:

    • One significant risk of anthracycline antibiotics is potentially irreversible damage to heart muscle cells, with limits on cumulative dosing.
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Page 28: ANTITUMOR ANTIBIOTICS

  • Action:

    • They block cell growth and the spread by interfering with DNA replication.

    • Cell cycle nonspecific actions (except for bleomycin, which primarily acts in the G2 phase).

  • Uses:

    • Treat a variety of solid tumors and hematologic malignancies, including leukemia, ovarian cancer, breast cancer, bone cancer, and squamous cell carcinomas.
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Page 29: Table 17.4 Antitumor Antibiotics

Anthracycline Antibiotic Agents:

  • daunorubicin

  • doxorubicin

  • epirubicin

  • idarubicin

  • valrubicin

Nonanthracycline Antibiotic Agents:

  • bleomycin

  • dactinomycin

  • mitomycin-C

  • mitoxantrone
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Page 30: ANTITUMOR ANTIBIOTICS

  • Produced from the mold Streptomyces.

  • Common toxicity: Bone marrow suppression.

  • Bleomycin:

    • Associated with pulmonary toxicity, pulmonary fibrosis, and pneumonitis.

  • Daunorubicin:

    • Can lead to heart failure; urine may turn reddish.

  • Doxorubicin:

    • Associated with left ventricular heart failure.
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Page 31: ANTITUMOR ANTIBIOTICS ADVERSE EFFECTS

Expected Side Effects:

  • Alopecia, fatigue, nausea, vomiting, mouth sores, anemia, bruising, and bleeding.

Adverse Reactions:

  • Heart failure, bone marrow suppression, pulmonary fibrosis (specific to Bleomycin).

  • Cardiomyopathy with high doses of Doxorubicin.

  • Routine cardiac monitoring is recommended (using MUGA scans).

  • Cytoprotective drugs such as dexrazoxane may mitigate risks of cardiac toxicity.
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Page 32: TOPOISOMERASE INHIBITORS OVERVIEW

  • Considered cell-cycle-specific drugs; most active during S and early G2 phases.

  • They interfere with cell growth and DNA synthesis by disrupting topoisomerase enzymes, essential for DNA maintenance.

  • Types:

    1. Topoisomerase I inhibitors

    2. Topoisomerase II inhibitors
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Page 33: TOPOISOMERASE INHIBITORS

  • Action:

    • Inhibit cell division and growth by causing DNA damage and blocking the cell cycle.

  • Uses:

    • Effective against colorectal, lung, pancreatic, ovarian, breast cancers, and hematological cancers.

  • Expected Side Effects:

    • Alopecia, nausea, vomiting, fatigue, mouth sores, diarrhea, appetite loss.

  • Adverse Reactions:

    • Bone marrow suppression, GI issues, hypersensitivity reactions, liver, and kidney impairment, interstitial lung disease.
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Page 34: Table 17.5 Topoisomerase Inhibitors

Topoisomerase I Inhibitors:

  • irinotecan

  • topotecan

Topoisomerase II Inhibitors:

  • etoposide

  • mitoxantrone

  • teniposide
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Page 35: TOPOISOMERASE 1 INHIBITORS (CAMPTOTHECINS)

Adverse Effects:

  • Topotecan:

    • Bone marrow suppression, nausea, vomiting, diarrhea, headache, rash, muscle weakness, cough.

  • Irinotecan:

    • More severe adverse effects than topotecan; notable for hematologic effects and cholinergic diarrhea.
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Page 36: MITOTIC INHIBITORS OVERVIEW

  • Also referred to as antimitotic agents.

  • They are cell-cycle-specific drugs derived from plant alkaloids targeting microtubules.

  • Subcategories:

    1. Taxanes

    2. Vinca alkaloids

  • Notably cause peripheral neuropathy, a potential permanent side effect.
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Page 37: MITOTIC INHIBITORS

  • Action:

    • Disrupt microtubule formation necessary for cell division, also causing general cellular damage.

  • Uses:

    • Effective for cancers of the breast, lung, ovary, lymphoma, and leukemia.

  • Expected Side Effects:

    • Nausea and vomiting, joint pain or stiffness, skin reactions.

  • Adverse Reactions:

    • Severe peripheral neuropathy, bradycardia, bone marrow suppression.
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Page 38: Table 17.6 Antimitotic Agents

Taxanes:

  • cabazitaxel

  • docetaxel

  • paclitaxel

Vinca Alkaloids:

  • vinblastine

  • vincristine

  • vinorelbine
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Page 39: ADVERSE REACTION: NEUROPATHY

  • Neuropathy can be permanent, with symptoms such as:

    • Numbness, tingling, difficulty walking and maintaining balance.

    • Severe constipation due to autonomic neuropathy.

    • Hearing loss may occur due to neuropathy.
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Page 40: Ā§ Assessing Neuropathy

  • Assess patient walking ability and balance.

  • Inquire about symptoms of numbness, tingling, pain, or loss of sensation in extremities.

  • Special considerations for patients with hereditary neuropathy (e.g., Charcot-Marie-Tooth disease).
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Page 41: COMBINATION CHEMOTHERAPY

  • Typically involves using a combination of chemotherapy drugs to maximize cell cycle kill.

  • Combining cell-cycle specific and nonspecific drugs enhances efficacy against cancer throughout the cell cycle.

  • Increased side effects and damage to normal tissues are a consequence of combination therapy.
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Page 42: MISCELLANEOUS ANTINEOPLASTICS

Example drugs:

  • Bevacizumab (Avastin):

    • An angiogenesis inhibitor that blocks the blood supply to tumors.

    • Used for metastatic colon cancer, rectal cancer (with 5-FU), non-small cell lung cancer, and malignant glioblastoma.

  • Hydroxyurea (Hydra, Droxia):

    • Similar action to antimetabolites; treats squamous cell carcinoma and some leukemias.

    • Adverse effects: edema, drowsiness, headache, rash, hyperuricemia.
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Page 43: MISCELLANEOUS ANTINEOPLASTICS CONTINUED

  • Imatinib (Gleevec):

    • Treats chronic myeloid leukemia (CML); a targeted therapy but not a monoclonal antibody.

    • Inhibits an active CML enzyme, potential for severe drug interactions observed.

  • Mitotane (Lysodren):

    • Adrenal cytotoxic drug specifically used for inoperable adrenal corticoid carcinoma.

    • Adverse effects: CNS depression, rash, nausea, vomiting.
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Page 44: MISCELLANEOUS ANTINEOPLASTICS CONTINUED

  • Octreotide (Sandostatin):

    • Manages carcinoid crisis conditions and diarrhea caused by vasoactive intestinal peptide-secreting tumors.
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Page 45: HORMONE THERAPY

  • Certain hormones promote the growth and rapid division of hormone-sensitive cancers (e.g., prostate and breast cancers).

  • Reducing hormone levels in sensitive tumors can slow their growth for extended periods, although this may not lead to a cure.
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Page 46: HORMONE THERAPY FOR BREAST CANCER

Mechanism:

  • Estrogen promotes the growth of some breast cancers; hormone therapy aims to reduce estrogen availability, inhibiting cancer growth.

Duration of Therapy:

  • Generally long-term, typically at least five years or until disease progression occurs.
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Page 47: HORMONE THERAPY FOR BREAST CANCER DRUG CATEGORIES

  • Categories include:

    • Aromatase inhibitors (AIs)

    • Selective estrogen receptor modulators (SERMs)

    • Estrogen receptor antagonists (ERAs)

    • Luteinizing hormone-releasing hormone (LHRH) agonists
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Page 48: Table 17.7 Hormone Therapy for Breast Cancer

Drug Category

Drug Name

Usual Dose

Aromatase inhibitors (AIs)

anastrozole (Arimidex)

1 mg orally daily

exemestane (Aromasin)

25 mg orally once daily

letrozole (Femara)

2.5 mg orally once daily

Selective estrogen receptor modulators (SERMs)

tamoxifen (Nolvadex, Soltamox)

20-40 mg orally once daily

raloxifene (Evista)

60 mg orally once daily

Estrogen receptor antagonists

fulvestrant (Faslodex)

60 mg orally once daily

LHRH agonists

goserelin (Zoladex)

Initial: two 250 mg IM injections on days 1, 15, 29; maintenance: same dose once monthly

leuprolide (Fensolvi, Lupron)

3.6 mg subcutaneously every 28 days

triptorelin (Trelstar, Triptodur)

11.25 mg subcutaneously once every 3 months for 2 years

3.75 mg IM once monthly

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Page 49: HORMONE THERAPY FOR BREAST CANCER CONTINUED

Drug Mechanisms:

  • Aromatase Inhibitors (AIs):

    • Inhibit aromatase, the enzyme converting androgens into estrogens, slowing tumor growth.

  • Selective Estrogen Receptor Modulators (SERMs):

    • Block estrogen receptors on breast cancer cells, inhibiting their growth.

  • Estrogen Receptor Antagonists (ERAs):

    • Block estrogen from binding to its receptor, decreasing estrogen's growth-promoting effects.

  • LHRH Agonists:

    • Stimulate FSH/luteinizing hormones, leading to ovarian shrinkage and reduced estrogen production over 4 weeks.
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Page 50: HORMONE THERAPY FOR BREAST CANCER COMMON SIDE EFFECTS

Side Effects:

  • Return of perimenopausal symptoms for women pre-menopause; heavier, irregular menses.

  • Bone, muscle, and joint pain.

  • Adverse Effects:

    • Increased serum cholesterol, fluid retention (peripheral edema), elevated blood pressure, increased stroke and heart attack risk.
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Page 51: HORMONE THERAPY FOR PROSTATE CANCER

Mechanism:

  • Prostate cancers have androgen receptors and growth is augmented when these receptors bind testosterone.

  • Suppressing androgen production or function is critical in slowing prostate cancer cellular growth.
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Page 52: HORMONE THERAPY FOR PROSTATE CANCER DRUG CATEGORIES

Categories include:

  • Androgen receptor antagonists

  • LHRH agonists

  • LHRH antagonists
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Page 53: Table 17.8 Hormone Therapy for Prostate Cancer

Drug Category

Drug Name

Usual Maintenance Dosages

Androgen