Chemotherapy and Drug Therapy Quiz

Antineoplastics Chemotherapy

• Antineoplastics chemotherapy is a treatment for cancer
• Chemotherapy targets various aspects of cancer treatment
• Includes different categories of drugs with specific mechanisms of actions
• The course covers the 2024-2025 curriculum for PHAR1059

Antineoplastic Drug Therapy

• Chemotherapy, hormonal, targeted drug therapies, and supportive drug therapies are types of antineoplastic drug therapies

Chemotherapy

• General Mechanism of Action: Cytotoxic but not Tumoricidal
  • Kills cells, including cancer cells
  • Stops cancer cells from dividing and growing
  • Shrinks tumors in size
  • Not specific to tumor cells
• General Mechanism of Action: Tumoricidal
  • Kills only tumor cells
  • More specific and targeted mechanism of action

Chemotherapy (Effects and Pharmacokinetics)

• Effective on rapidly dividing cells
• Narrow margin between therapeutic effects and toxicity
• Many adverse effects
• Drug combinations are often more effective
• Resistance to drugs can develop
• Dosing varies based on cancer type, previous treatment, and administered drugs
• Body surface area (m²) is commonly used to calculate the dose

Chemotherapy (Adverse Effects)

• Describes side effects of a drug or treatment that are serious enough to prevent increasing the dose or level of treatment
• Targets normal rapidly dividing healthy cells. Many adverse effects relate to these cells
  • Bone marrow suppression (neutropenia, thrombocytopenia, anemia)
  • Hair loss (hair follicles)
  • Gastrointestinal issues (diarrhea, mucositis, nausea and vomiting)
  • Teratogenic risks versus benefits in pregnancy
  • Infertility, IV form risk of extravasation

Chemotherapy - Cell Cycle Specific

• Cytotoxic during a specific phase of the cell cycle
• Frequently used for solid tumors and circulating tumors
• Does not work on resting or dormant phase cells
• Includes several classes:
  • Antimetabolites
  • Mitotic Inhibitors
  • Topoisomerase Inhibitors
  • Antineoplastic enzymes

Chemotherapy - Cell Cycle Specific (Classes)

• Antimetabolites: Structurally similar to normal cellular metabolites; interfere with cellular growth by disrupting synthesis or actions of several component needed for cell reproduction.
  • Mechanism: Falsely substitutes purines, pyrimidines, and folic acid
  • Mechanism: Inhibits crucial enzymes involved in synthesis of purines, pyrimidines, and folic acid
  • Cell-cycle phase target: S phase (DNA synthesis)
• Mitotic Inhibitors: Plant-derived compounds that target various phases of the cell cycle, particularly mitosis (cell division).
• Topoisomerase Inhibitors: Newer class of chemo drugs derived from a Chinese shrub (camptotheca). Binds to the DNA- topoisomerase I complex during the S phase; inhibits proper DNA functioning by slowing/breaking DNA strands

Chemotherapy - Antimetabolites

• Folate Antimetabolites: Includes Methotrexate, Pemetrexed, Raltitrexed (Tomudex®)
  • Mechanism: Inhibits enzyme needed to activate folic acid into its active form (folate), needed for DNA synthesis.
  • Result: DNA synthesis is suppressed, leading to cell death
  • Indications: Solid tumors of the head, neck, breast, lung & leukemia; lymphomas; Pemetrexed (lung cancer only); and Raltitrexed (colorectal cancer)
• Purine Antimetabolites: Include Cladribine, Fludarabine (F-AMP), Mercaptopurine (6-MP), Thioguanine (6-TG)
  • Mechanism: Act as synthetic forms of adenine and guanine (purines) and disrupt RNA and DNA synthesis
  • Indication: Leukemia and Lymphoma
• Pyrimidine Antimetabolites: Includes Capecitabine, Cytarabine (ara-C), Fluorouracil (5-FU), Gemcitabine
  • Mechanism: Acts as synthetic forms of cystine and thymine (DNA) and uracil and cytosine (RNA); incorporate into the metabolic pathways for DNA and RNA synthesis, disrupting RNA/DNA production
  • Administration: Mostly intravenous (except capecitabine - oral)

Chemotherapy - Adverse Effects, Specific Antimetabolites

• Nausea, vomiting, diarrhea, hair loss
• Bone marrow suppression (methotrexate)
• Lung and liver damage (methotrexate)
• Neuro damage (methotrexate)
• Peripheral neuropathy

Chemotherapy - Mitotic Inhibitors

• Plant-derived compounds
• Targets various phases of the cell cycle (G2 or during mitosis)
• Slows cell division
• Indications: Variety of solid tumors, some hematological cancers
• Synergistic use with other drugs

Chemotherapy - Mitotic Inhibitors (Subclasses)

• Vinca Alkaloids: Derived from periwinkle and mandrake plants; interfere with mitotic spindle structures during M phase, inhibits cell reproduction, causes cell death, Vinblastine, Vincristine, Vinorelbine
• Taxanes: Derived from bark of yew trees; acts on late G2 phase and M phase; high risk adverse effects during infusion, requires highly trained nurse administration, Paclitaxel, Docetaxel.

Chemotherapy - Mitotic Inhibitors Adverse Effects/Events

• Hair loss
• Nausea and vomiting
• Bone marrow depression
• Nephrotoxicity
• Hepatotoxicity
• High risk of extravasation
• Antidote use/ need is Hyaluronidase SC.
• Warm compresses indicated

Chemotherapy - Topoisomerase Inhibitors

• Topoisomerase II Inhibitors: Etoposide, Teniposide; inhibit topoisomerase II, breaks DNA strands, targets late S phase and G2 phase of cell cycle
• Topoisomerase I Inhibitors: Topotecan, Irinotecan; newer class of chemo-drugs, semi-synthetic drug derived from Chinese shrub; binds to DNA-topoisomerase I complex during S phase, inhibits proper DNA functioning by slowing and breaking DNA strands
• Indications: Ovarian cancers, colorectal cancer, small cell lung cancer.
• Administration: Injectable only

Chemotherapy - Topoisomerase Inhibitors (Adverse Effects)

• Stomatitis
• Hair loss
• Mild gastrointestinal upset (GI)
• Severe diarrhea
• Lacrimation (excessive tears)
• Sweating
• Bone marrow depression
• Cardiovascular Toxicity, Pulmonary Embolism, Cerebral Vascular Accident, Myocardial Infraction
• Special Notes: Etoposide-contains diluent that may cause hypotension, risk of orthostatic hypotension when used for testicular cancer

Chemotherapy - Antineoplastic Enzymes

• Use of enzymes produced in bacteria using recombinant technology
• Make cells unable to synthesize asparagine (required for G1 DNA synthesis and cell survival)
• Indications: Lymphocytic leukemia— Pegasparagase
• Administration: Injectable only

Chemotherapy - Antineoplastic Enzymes (Adverse Effects)

• Allergic reactions are common
• Impaired pancreatic function
• Hyperglycemia
• Pancreatitis

Chemotherapy - Cell Cycle Non-Specific

• Cytotoxic to neoplasms at any phase of the cell cycle
• Includes two broad categories
  • Alkylating drugs
  • Cytotoxic antibiotics
• Chemotherapeutic agents emerged in the 1940s; the first was an alkylating drug developed from mustard gas (nitrogen mustard).

Chemotherapy - Cell Cycle Non-Specific (Alkylating drugs)

• Alkylation = process where alkyl group moves from one molecule to another in DNA leading to faulty chemical bonds between DNA strands
• Defective DNA leads to DNA damage; prevents reproduction and causes cell death
• Used to treat solid and circulating cancers with three categories.
• Classic Alkylators (Nitrogen Mustards)
  • Cyclophosphamide
  • Chlorambucil
  • Isofamide
  • Melphalan
• Nitrosoureas
  • Carmustine
  • Lomustine
  • Streptozocin
• Miscellaneous Alkylators
  • Busulfan
  • Carboplatin
  • Cisplatin
  • Dacarbazine
  • Procarbazine hydrochloride
  • Temozolimide
• Adverse effects Include similar dose limiting effects and nephrotoxicity, neurotoxicity, bone marrow suppression, ototoxicity, pulmonary fibrosis

Chemotherapy - Cell Cycle Non-Specific (Cytotoxic Antibiotics)

• Natural or semi-synthetic substances derived from mold
• Classified by mechanism of action (intercalation—inserts molecules between two DNA strands to cause strand breaks and programmed cell death).
• Inhibit topoisomerase II
• Generate free radicals causing DNA strand breaks resulting in programmed cell death
• Indications: Solid tumors and hematological cancers
• Anthracyclines (Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Valrubicin)
• Other cytotoxic antibiotics (Bleomycin, Dactinomycin, Mitomycin, Mitoxantrone)

Chemotherapy - Cell Cycle Non-Specific (Adverse Events)

• Hair loss
• Nausea and vomiting
• Bone marrow suppression
• Hepatotoxicity
• Pulmonary toxicity (pulmonary fibrosis and pneumonitis)
• Heart failure and cardiomyopathy
• Drug interactions (especially with Digoxin)

Hormonal Antineoplastics

• Often not considered a type of chemotherapy
• Sex hormones accelerate cancer growth
• Mechanism of action targets to block body's sex hormone receptors OR by administering hormones with opposing effects

Hormonal Antineoplastics (Breast Cancer)

• The growth of some breast cancer cells is moderated by estrogen; increasing cancer growth
• "Estrogen receptor-positive breast cancer"
• Blocking estrogen production or utilization can slow growth; Tamoxifen (Nolvadex-D), Toremifene (Fareston)

Hormonal Antineoplastics (Breast Cancer- Modulators)

• Types of Selective Estrogen Receptor Modulators (SERMs)
  • Anastrozole
  • Exemestane
  • Letrozole
• Anti-estrogen effects can be present on breast tissue and may be proestrogenic in uterine tissue
• Prevents Aromatase formation: inhibits the action for synthesis of estrogen and cannot be used with Tamoxifen.

Hormonal Antineoplastics (Prostate Cancer)

• Prostate cancer can be affected by testosterone increasing the growth levels
• Hormones interfere with a production of testosterone ,or compete with androgen receptors
• Androgen Deprivation Therapy
  • Bicalutamide (Casodex)
  • Flutamide (Eulexin)
  • Emcyt (Estramustine)

Hormonal Antineoplastics (Adverse Effects)

• Female Specific:
  • Menopausal-like symptoms
  • Hot flashes
  • Night sweats
  • Irregular periods
  • Increased osteoporosis risk
  • Increased risk of endometrial cancer
• General:
  • Fatigue
  • Infertility; impotence
  • Increased blood clot risk ;Increased cholesterol levels that increase cardiovascular risks

Targeted Drug Therapy

• Focuses on cancer drug research
• Uses drugs targeted to specific molecules involved in cancer cell growth, while sparing healthy cells
• Includes Imatinib (tyrosine inhibitor) Vorinostat (histone deacetylase inhibitor)

Targeted Drug Therapy (Immunotherapy)

• Uses the body's immune system to target cancer cells
• Includes:
  • Hematopoietic or Colony Stimulating Factors Agents: Increase immunity in patients affected via chemotherapy
  • Monoclonal Antibodies (MABs): Trigger immune system to attack/kill cancer cells
  • Angiogenesis Inhibitors: Inhibit/restrict growth of the new blood supply to tumors.
  • Interferons and Interleukins-2 (cytokines): Improve the immune system to target cancer cells.
  • Immunostimulants: Used to stimulate the production of immune cells—or antibodies that target cancer cells
• CAR-T Cells (Chimeric Antigen Receptor T-cells):
  • Modifies patients T-cells in a lab
  • Used as a standard treatment for patients with relapsed leukemia, and for new trials with some relapsing solid tumors.

Supportive Drugs

• Used to offset damaging effects of cancer treatment
• Includes:
  • Chemo-protective
  • Radio-protective
  • Cyto-protective
• Not considered a type of chemotherapy treatment
• Protects cells and organs from side effects in combination of chemotherapy and/ or radiation therapy

Supportive Drugs (Specific Drugs and Mechanism of Action)

• Allopurinol (Zyloprim): Prevents uric acid buildup (during leukemia or lymphoma treatment)
• Rasburicase (Fasturtec): Helps clear uric acid from the blood
• Dexrazoxane (Zinecard): May prevent damage from doxorubicin (used to prevent complications of some types of cancer therapy)
• Folinic acid (leucovorin): Protects from damage via methotrexate by increasing the production of blood cells.
• **Colony-stimulating factors (e.g., Filgrastim):**Lowers the risk of low blood cell counts by stimulating the bone marrow increase the production of blood cells.

General Patient Education

• Understanding the treatment protocol (treatment plan); adverse effects
• Educate on signs of infections; bleeding; Anemia
• Prevention of hair loss
• Maintain mouth hygiene
• Prevention of exposure to others with infections
• Manage diarrhea
• Fluid intake management to 3 liters per day
• Precautions to avoid risks of bleeding (ASA or Ibuprofen)
• Contraceptives/ reproductive support prior to treatment
• Use of reliable resources such as Canadian Cancer Society.

Nursing Considerations

• Establish a therapeutic relationship; offer support; labs
• Monitor electrolytes, minerals, uric acid levels,complete blood count (CBC), platelets, bleeding times, liver and renal function
• Check neutrophil counts; signs of infections
• Presence of infection— or Febrile Neutropenia (Fever associated with Neutropenia)
• Monitor tumor markers(tumour marker may be used to monitor the effectiveness of treatment); oral mucosa, swallowing, weight, nutritional status, bowel patterns, N&V
• Signs of infection, bleeding, anemia
• Antiemetics 30-60 minutes before treatment or/and meals
• Be aware of look-alike, sound-alike drug names
• Safe handling and certification, PPE, spill kits
• Monitor IV site closely; extravasation protocols
• Patency of central lines
• Double flush of bodily secretions; reverse isolation protocol when required
• Use reliable resources (Canadian Association of Nurses in Oncology).

Test your knowledge on chemotherapy and drug therapy focused on cancer treatment. This quiz covers drug classes, mechanisms of action, and adverse effects associated with chemotherapy. Dive deep into the intricacies of how these drugs target cancer cells during various cell cycle phases.