Chemotherapeutic Agents

NSC 330: Chemotherapeutic Agents

The Cell Cycle

• Definition: A series of intracellular events occurring from one cell division to the next.

Normal Cells

• Characteristics:
    - Reproduce according to a predetermined sequence of events.
    - Well differentiated (specific functions).
    - Reproduce in response to a need:
      - Stop reproduction when the need for new cells has been met.

Malignant Cells

• Characteristics:
    - Reproduce with the same sequence of events as normal cells but grow in an uncontrolled manner.
    - Do not differentiate or mature or function like normal cells.
    - Proliferate indefinitely, meaning they can increase rapidly in numbers.

• Neoplasm: Abnormal growths of new tissue that can be classified as benign or malignant.

Chemotherapy

• Types:
    - Primary Induction: The initial chemotherapy administered before additional cancer treatments.
      - Indicated for patients with advanced disease.
    - Neoadjuvant Therapy: Systemic therapy given prior to surgery or radiation

  • drug therapy first, then surgery
      - Adjuvant Therapy: Administered alongside surgery and/or radiation.
      - Direct Installation: Localized treatment to the affected region, drug is directly into the tumor

Characteristics of Antineoplastic Agents

• Primary Actions:
    - Cytotoxic: Most kill malignant cells by interfering with cell replication, act during specific phases of the cell cycle
    - Cell Cycle Specific: More effective when administered continuously (e.g., via prolonged infusion or multiple small doses).
    - Cell Cycle Non-Specific: More effective when administered intermittently.

Antineoplastic Agents

• Key Characteristics:
    - Most are active against rapidly-dividing and proliferating cells.
    - Each dose of an antineoplastic drug kills some but not all malignant cells.
    - Administration Routes: Primarily oral (PO) or intravenous (IV).
    - Risk of inducing drug-resistant malignant cells.
    - Many are potential teratogens (harmful to fetus).

Cell Cycle Specific vs. Non-specific

• Cell-Cycle Specific Drugs: Work during a specific phase of the growth cycle. Effective for high growth fraction malignancies.

• Cell-Cycle Non-Specific Drugs: Work during any phase of the cell cycle. Effective for both low growth fraction malignancies (solid tumors) as well as high growth fraction malignancies.

Agent Classification

• 1. Alkylating Agents: Cell cycle nonspecific, toxic to tissues with high growth factor, hepatotoxic: assess liver function BEFORE
    - Example: cisplatin.

• 2. Antimetabolites: Similar to necessary nutrients for cell reproduction.
    - Causes depletion of necessary substances or abnormal DNA formation.
    - Example: fluorouracil.

• 3. Plant Alkaloids: Inhibit cell division, Cell-cycle specific.
    - Example: vincristine.

• 4. Antitumor Antibiotics:
    - Some anti-infective activity but too toxic for general antibiotic use.
    - Cardiac toxicity with doxorubicin (causes dysrhythmias).
    - Pulmonary toxicity with bleomycin (causes respiratory complaints).

• 5. Hormones & Hormone Inhibitors:
    - Alter the hormonal environment that promotes cancer growth.
    - Goal is to bind to estrogen receptors and prevent activation by estradiol

• daily dosing (up to 5 years)
    - Tamoxifen.
      - Indication: Estrogen receptor-positive breast cancer.
      - Adverse Effects (AE): Hot flashes, menstrual irregularity, bone pain.
      - Risk of endometrial cancer in females with an intact uterus.
      - Use barrier contraception in sexually active, pre-menopausal patients up to 2 months post-therapy.
    - Anastrozole.
      - Class: Aromatase inhibitor: Reduces estrogen production in ovaries and other tissues

• prevent/treat recurrence of estrogen-responsive breast cancer
      - Commonly used after 2-3 years of Tamoxifen
      - Adverse Effects: Hot flashes, nausea, edema.
    - Flutamide
      - Class: Antiandrogen.
      - Treats advanced prostate cancer by blocking testosterone effects.
      - Adverse Effects: Hot flashes, nausea/vomiting/diarrhea (N/V/D), hepatotoxic.

Common Adverse Effects of Antineoplastic Agents

• 1. Bone marrow depression:
    - Decreased neutrophils (risk of infection), thrombocytes (risk of bleeding), and erythrocytes (risk of anemia).

• 2. Toxic effects on GI lining:
    - Symptoms: Nausea/Vomiting, stomatitis (inflammation of the mouth), diarrhea, impairment of nutrient absorption.

• 3. Toxic effects on hair follicles:
    - Symptom: Alopecia (hair loss).

Drugs Used to Reduce Toxicity

• 1. Dexrazoxane: Reduces cardiac toxicity associated with doxorubicin.

• 2. Erythropoietin:
    - Treats chemotherapy-induced anemia.
    - Dosage: 150 units/kg subcutaneously (SC) 3 times/week.
    - Adjust according to hematocrit
    - Effectiveness may take 2-4 weeks; may eliminate need for blood transfusion.

• 3. Filgrastim:
    - Treats chemotherapy-induced neutropenia.
    - Administration: SC or IV, at a dose of 5 micrograms/kg daily (for up to 2 weeks or until absolute neutrophil count reaches 10,000 cells/mm³).

General Nursing Considerations

• 1. Special training is required

• 2. CBC with differential should be done before each cycle of chemotherapy.

• 3. Management of Nausea/Vomiting (N/V):
    - Administer antineoplastic drugs at bedtime.
    - Antiemetics to be given before treatment and regularly for 48 hours afterwards (e.g., Ondansetron or Dexamethasone).

• 4. Stomatitis Management:
    - Use viscous lidocaine as a mouth and throat anesthetic; assess swallowing and toleration of food temperature.
    - For oral infections, local nystatin can be employed.

• 5. Extravasation (especially with doxorubicin and vincristine):
    - Recommendations:
      - Avoid placing IV in small veins; inject IV dose rapidly into rapidly flowing intravenous fluids.
      - Flush the vein 2-5 minutes after drug administration.

• If extravasation occurs:
    1. Stop the infusion.
    2. Attempt to aspirate.
    3. Apply heat to the area.
    4. Be aware this may lead to surgical debridement and skin grafting.
    5. Note institution-specific protocols.

Hyperuricemia Management

• Cause: Rapid breakdown of malignant cells.

• Recommendations:
    - Maintain high fluid intake to promote urination.
    - Potential need for allopurinol to inhibit uric acid formation.

Combination Therapy in Chemotherapy

• Recommendations: Use agents with different mechanisms of action and minimal overlapping toxicities.

• Advantages:
    - Increased therapeutic effects.
    - Decreased adverse effects (AEs).
    - Suppressed drug resistance.
    - Decreased injury to normal cells.

General Administration Guidelines

• Drugs are usually given in high doses on intermittent schedules, minimizing immunosuppression and allowing periods for tissue recovery.

• Dosage calculations are based on body weight.

• Handling Antineoplastic Drugs:
    - Precautions include avoiding contact with the drug solution, wearing protective gear (gloves, gowns, eye protection), and if handling powder forms, wearing a mask to prevent inhalation.
    - Prepare cytotoxic drugs on disposable trays/towels to contain spills.
    - Dispose of waste as per specialized regulations.

Immunosuppressive Agents

• Definition: Damage or kill dividing cells, especially immunologically competent lymphocytes.

• Example: Methotrexate.
    - Mechanism of Action (MOA): Folate inhibitor that inhibits lymphocyte proliferation.

• Uses:
    - High doses for cancer treatment.
    - Low doses for juvenile rheumatoid arthritis, severe psoriasis (scaly skin).

• Adverse Effects:
    - Stomatitis.
    - Nausea/Vomiting/Diarrhea (N/V/D).
    - Thrombocytopenia (low platelet count).

Further Adverse Effects of Immunosuppressive Agents

• Potential adverse effects include:
    - Erythrocytopenia (low red blood cell count).
    - Alopecia (hair loss).
    - Photosensitivity (increased skin sensitivity to sunlight).
    - Renal toxicity (toxic effects on kidneys).
      - Important to keep the patient well hydrated during treatment.
    - Hepatotoxic (toxic effects on the liver).
    - Teratogenic effects (causing developmental abnormalities in a fetus).

Nursing Implications for Immunosuppressive Agents

• Key Nursing Considerations:
    - Closely observe for bleeding events.
    - Monitor for signs of infections due to impaired immune function.
    - Monitor renal function
    - Observe for potential hepatotoxicity
    - Advise patients to wear sunscreen.
    - Recommend using reliable forms of contraception
    - Encourage maintaining a healthy lifestyle
    - Suggest wearing a medic-alert bracelet for safety
    - Be aware of pregnancy category X risks associated with certain drugs.