Chemotherapy Agents: General Adverse Effects

Part 1: General Overview

Instructor: Kenneth Mueller, PharmD, BCPS

Lecture Objectives

Describe and manage common adverse effects of chemotherapy/anti-neoplastic agents
Describe the term "Nadir"
Identify, manage, and prevent "Febrile Neutropenia"
Review appropriate labs and terminology for Bone Marrow Suppression (WBC, RBC, Plts)
Compare/Contrast Infiltration vs Extravasation including signs/symptoms, management, and drug culprits
Assess, Monitor, Manage, and Evaluate Tumor Lysis Syndrome

Drugs to Know

WBC Agent/Colony Stimulating Factor (CSF):
- Filgrastim
RBC Agent/Erythropoietin Stimulating Agent (ESA):
- Epoetin Alfa
- Darbepoetin Alfa
Review:
- Xanthine Oxidase Inhibitors: Allopurinol

Importance of Pharm

A quiz question example:
- "Don't decrease the metabolic capacity of intestinal CYP3A4" refers to:
- C. No grapefruit juice with meds

Chemotherapy Mechanism

General Mechanism: Most chemotherapy drugs work by suppressing rapidly proliferating cells:
  - Good: Slows down or destroys cancer (tumors)
  - Bad: Targets normal cells in high turnover areas:
    - GI Tract Cells:
      - GI Ulcers, Stomatitis, Mucositis
    - Bone Marrow:
      - Pancytopenia, Blood Dyscrasias, Aplastic Anemia
      - Neutropenia, Anemia, Thrombocytopenia
    - Hair Follicles:
      - Alopecia

Management for Chemotherapy Patients

Bone Marrow Suppression:
  - Neutropenia: Infection Risk/Safety
  - Anemia: Signs/Symptoms (S/S) and Management
  - Thrombocytopenia: S/S and Management
Administration Concerns:
- Infiltration/Extravasation: S/S and Management
- Disposal and Personal Protective Equipment (PPE)
GI Tract Concerns:
- Nausea/Vomiting
- Oral Care, GI irritation/ulceration
Other Patient Safety Concerns:
  - Alopecia
  - Tumor Lysis Syndrome
  - Sexual/Reproductive Health

Neutropenia and Nadir

Neutropenia: Deficiency in Neutrophils
Nadir:
- Refers to the lowest point after chemotherapy when many cell lineages die
- Highest risk for infection due to low white blood cells (WBC)
Monitoring:
  - WBC and Neutrophil Count
  - Frequent temperature monitoring (every 4 hours)
  - Don't give chemotherapy if Absolute Neutrophil Count (ANC) < 1000
Lab Measures:
- Normal Range for WBC: 5,000-10,000 cells/mm³
- Normal Range for ANC: > 1,500 cells/mm³

Expected Temperature Ranges

Oral temperature range: 36° to 38° C (96.8° to 100.4° F); average: 37° C (98.6° F)
Rectal temperatures: Usually 0.5° C higher than oral
Axillary temperatures: Usually 0.5° C lower than oral
Important Note:
- If a patient develops a fever, it is considered an emergency: "Febrile Neutropenia"

Febrile Neutropenia

If a neutropenic patient develops a fever, it indicates a potential infection.
Medical emergency:
- If at home, go straight to emergency department.
- Start antibiotics immediately (STAT)
Patient Safety/Risk Reduction Precautions:
  - Limit unnecessary procedures
  - Live vaccines are NOT recommended
  - Limit visitors, especially sick or ill ones
  - Avoid flowers/potted plants due to microorganisms
  - Cook and clean fruits and vegetables thoroughly
  - No raw fruits/vegetables
  - Misconception: “I will avoid crowds to keep from infecting others.” (Incorrect logic; risk for infection remains acute)

Granulocyte Colony Stimulating Factor (G-CSF): Filgrastim

Used to treat:
- Severe Chronic Neutropenia
- Chemotherapy-induced Neutropenia
Mechanism of Action:
- Stimulates bone marrow to produce more neutrophils
Administration Consideration:
  - Give 24 hours or later after chemotherapy
  - Monitor Complete Blood Count (CBC) biweekly (WBC/ANC)
  - Hold if WBC > 10,000 or ANC > 1,000
Monitoring Goals:
- Target ANC: 1,000 cells/mm³

Adverse Effects of Filgrastim

Common Adverse Effects:
  - Bone pain in 25% of patients (due to bone marrow stimulation)
  - Leukocytosis (excess WBC production) controlled by frequent monitoring
  - Hold medication if WBC are elevated

Administering Filgrastim

Administration Guidelines:
  - Do not give within 24 hours of chemotherapy
  - Administer via IV or subcutaneous (SUBQ) routes
  - Do NOT shake or re-use vials
  - Usage Note: Single-use only due to high cost

Erythropoietin Stimulating Agents (ESA): Epoetin Alfa

Used to treat anemia:
- Correct iron and vitamin stores beforehand
- Anemia in chronic kidney disease (CKD) and chemotherapy-induced anemia
Therapeutic Outcomes:
  - Goals for Hemoglobin and Hematocrit (H/H):
    - Hematocrit: Target towards normal range; don’t exceed limits.
    - Hemoglobin Goal: Maintain at < 11 gm/dL (hold if ≥ 11 gm/dL)

Adverse Effects of Epoetin Alfa

Common Adverse Effects:
  - Hypertension (most common)
  - Serious cardiovascular events: heart attack, stroke, heart failure, thrombosis, seizures
  - Risk of blood clots (DVTs/PEs) – due to rapid increase in hematocrit and hemoglobin ("Milk Shake Analogy")
Contraindications:
- Drug allergy, uncontrolled hypertension, head and neck cancers, risk of thrombosis

Nursing Considerations for Epoetin Alfa

Before Administration:
- Monitor blood pressure
- Monitor hemoglobin and hematocrit (H/H)

Administration Note for Epoetin Alfa

Administration Guidelines:
- Do NOT shake vials
- One-time single-use vial (do not reuse)

Summary of Bone Marrow Suppression Effects

Includes monitoring of:
  - White Blood Cells
  - Red Blood Cells
  - Platelets
Importance of identifying and managing general adverse effects of all chemotherapy regimens
Key Terms: "Nadir" and "Febrile Neutropenia"

Administration Techniques for Infiltration vs Extravasation

Infiltration

Definition: Non-tissue damaging medication infiltration
Signs/Symptoms: Swelling, slowed infusion, pallor, damp/cold bandage
Management Steps:
  1. Stop infusion
  2. Remove catheter
  3. Elevate the extremity, encourage range of motion
  4. Apply warm or cold compress depending on the infiltrate
  5. Check with the provider about drug administered
Prevention: Careful site selection and securement of catheter

Extravasation

Definition: Tissue damaging medication infiltration
Signs/Symptoms: Pain, burning, redness, erythema, swelling, warmth
Management Steps:
  1. Stop the infusion
  2. Attempt to withdraw solution from IV access
  3. Keep catheter in place to infuse an antidote if needed
  4. Elevate extremity and follow hospital protocol
Prevention: Use central line, chemotherapy-certified nurses only administer chemotherapy, use infusion pumps, monitor IV sites

Administration: Personal Protective Equipment (PPE)

Importance of Safe Handling: Proper disposal and use of PPE, including gloves, gown, hair and shoe covers, respiratory and facial protection
Chemotherapy Spill Protocols:
- Large Spill: Contact OSHA
- Small Spill: Use Chemotherapy Spill Kits: goggles, mask, protective clothing, absorbent pads, and disposal bags

GI Tract Concerns Related to Chemotherapy

Key Symptoms:
- Nausea (CINV) and Damage to GI Tract (Mucositis/Stomatitis)
Management Strategies:
  1. Pre-medication with ondansetron 1 hour before chemotherapy
  2. Follow-up doses as needed
  3. Non-pharmacological measures to reduce nausea (comfortable foods, manage fluid intake)

Alopecia and Tumor Lysis Syndrome

Alopecia: Hair loss due to chemotherapy targeting rapidly dividing cells; may grow back differently
Tumor Lysis Syndrome:
- Occurs from destruction of cancer cells releasing byproducts (uremic toxins)
- Treatment/Prevention includes hydration and Allopurinol

Sexual Health Considerations

Chemotherapy can impact fertility, sperm production, fetal development
Discuss contraception options and educate patients on potential reproductive effects.