Chemotherapy and Antiemetics Overview

Chemotherapy Agents

Chemotherapy and Antiemetics

Cancers

Solid Tumors

  • Types: Breast, Lung, Prostate, Colon, Rectum

  • Characteristics:
      - Low growth fraction
      - Respond poorly to drugs

Most Common Cancers

  • Examples:
      - Lymphocytic leukemia
      - Hodgkin's disease
      - Certain testicular cancers

  • Characteristics:
      - High growth fraction
      - Respond well to drugs
      - Rarer cancers have a high cure rate

Mitosis

Cell Cycle Overview

  • Phases of Cell Cycle:
      - G₁ Phase: Resting period before DNA synthesis starts.
      - S Phase: Synthesis of DNA, during which DNA is replicated.
      - G₂ Phase: Preparation for mitosis where components needed for mitosis are synthesized.
      - M Phase: Mitosis occurs, leading to cell division.

Chapter 2: Neoplastic Cells vs Normal Cells

Differences between Cancer Cells and Normal Cells

  • Unrestrained Growth and Division: Cancer cells proliferate without the usual regulatory mechanisms.

  • Metastasis: Cancer cells penetrate adjacent tissues, facilitating spread to other areas of the body.

  • Immortality: Cancer cells have the ability to divide indefinitely.

Basic Principles of Cancer Chemotherapy

Definitions and Treatment Methods

  • Definition of Cancer: Unregulated cellular proliferation.

  • Treatment Modalities:
      - Surgery: Direct removal of tumors.
      - Radiation: Targeting tumors with radiation therapy.
      - Drug Therapy:
        - Treatment of choice for disseminated cancers (examples: leukemia, widespread metastases).
        - Additionally, can be used as an adjunct to surgery and radiation.

Strategies for Successful Chemotherapy

Main Objectives

  • Identify Obstacles: Address the major obstacles to successful chemotherapy.

  • Strategies for Overcoming Obstacles: Discuss how these can be effectively managed.

  • Major Toxicities: Review common toxic effects of chemotherapeutic drugs and potential mitigation strategies.

Obstacles to Successful Chemotherapy

Key Challenges

  • Toxicity to Normal Cells: Chemotherapy often impacts healthy cells.

  • Need for 100% Cell Kill: To achieve a cure, all cancer cells must be eliminated.

  • Lack of Early Detection: Early detection is critical for effective treatment.

  • Response of Solid Tumors: Solid tumors typically respond poorly to chemotherapy.

  • Drug Resistance: Tumors can develop resistance to chemotherapy agents.

  • Heterogeneity of Tumor Cells: Variability within tumor populations complicates treatment.

  • Limited Drug Access: Not all drugs can effectively reach tumor cells.

Strategies for Maximizing Chemotherapy Efficacy

Techniques

  • Intermittent Chemotherapy: Administering chemotherapy intermittently can reduce toxicity while maintaining effectiveness.

  • Combination Chemotherapy: Utilizing multiple drugs can enhance treatment efficacy and reduce resistance.

  • Regional Drug Delivery: Specialist delivery methods include:
      - Intra-arterial: Directly into the blood vessel serving the tumor.
      - Intrathecal: Administered into the spinal canal.
      - Other Specialized Routes.

Major Toxicities of Cancer Chemotherapy

Common Side Effects

  • Chemotherapy agents tend to be most toxic to tissues with a high growth fraction.

  • Specific Toxicities Include:
      - Bone Marrow Suppression: Leads to neutropenia, thrombocytopenia, and anemia.
      - Alopecia: Loss of hair follicles.
      - Reproductive Toxicity: Particularly affects sperm production.
      - Digestive Tract Injury: Stomatitis, nausea, vomiting, and diarrhea.
      - Local Injury from Vesicants: Can cause severe tissue damage upon extravasation.
      - Hyperuricemia: Elevated levels of uric acid.

Making the Decision to Treat

Considerations in Treatment Decisions

  • Benefit-Risk Ratio: Benefits of treatment must balance against associated risks.

  • Informed consent: Patients need to be aware of the potential benefits of therapy, which may involve:
      - Cure of the disease.
      - Prolongation of Life: Extending survival even if not curative.
      - Palliation: Alleviating symptoms and improving quality of life.

Cytotoxic Agents

Classification and Management

  • Groups of Cytotoxic Agents:
      - Alkylating Agents: (e.g., Cyclophosphamide)
      - Antimetabolites: (e.g., Methotrexate)
      - Antitumor Antibiotics: (e.g., Doxorubicin)
      - Mitotic Inhibitors: (e.g., Vinca Alkaloids)

  • Nursing Management Involvement: Each group requires focused education regarding the specific medications used.

Alkylating Agents

Characteristics and Mechanism of Action

  • Types: Nitrogen Mustards, Nitroureas, Platinum Compounds.

  • Mechanism of Action: These agents kill rapidly dividing cells by interrupting DNA and RNA synthesis.
      - Cell Cycle Phase: Non-specific, acting across all phases.

  • Indications for Use: Treat a range of neoplastic diseases.

  • Adverse/Side Effects: Includes resistance development, severe bone marrow suppression, nausea, vomiting, alopecia, and acute hemorrhagic cystitis.

  • Client Teaching:
      - Importance of hydration and usage of protective agents like Mesna for hemorrhagic cystitis.
      - Consider selecting a hairpiece prior to experiencing alopecia.

  • Examples:
      - Nitrogen Mustards: Cyclophosphamide
      - Nitroureas: Carmustine
      - Platinum Compounds: Cisplatin

Antimetabolites

Types and Mechanism of Action

  • Categories:
      - Folic Acid Analogs,
      - Pyrimidine Analog,
      - Purine Analog

  • Mechanism of Action: Interrupt the S phase of cell reproduction leading to cell death.

  • Indications for Use: Designed primarily for various neoplastic diseases.

  • Specific Functions:
      - Folic acid analog disrupts DNA synthesis by preventing the conversion of folic acid to its active form.
      - Pyrimidine analog treats solid tumors.
      - Purine analog is S-phase specific for oral use in various cancers.

  • Adverse/Side Effects: Side effects include bone marrow suppression, nausea, vomiting, and alopecia.

  • Client Teaching:
      - Fluid encouragement (2-3 L/day) to monitor for uric acid buildup.

  • Examples:
      - Folic Acid Analogs: Methotrexate
      - Pyrimidine Analog: Fluorouracil
      - Purine Analog: Mercaptopurine

Antitumor Antibiotics

Mechanism of Action and Examples

  • Categories:
      - Anthracyclines (can damage the heart)
      - Non-anthracyclines (less cardiac harm)

  • Mechanism of Action: Prevent the synthesis of RNA, DNA, or proteins, leading to cell death.

  • Applications: Used to treat solid tumors and disseminated cancers (e.g., Hodgkin's lymphoma, non-Hodgkin's lymphoma, sarcomas).

  • Adverse Effects: Similar toxicity as other chemotherapy including bone marrow suppression, nausea, and severe tissue damage (particularly from vesicants) leading to alopecia.

  • Client Teaching:
      - Administer antiemetics before chemotherapy to manage nausea.

  • Example:
      - Anthracycline type: Doxorubicin

Mitotic Inhibitors

Overview of Action and Side Effects

  • Categories: Vinca Alkaloids, Taxanes

  • Mechanism of Action: Inhibit mitosis, preventing cell division.

  • Indications: Utilize for various neoplastic diseases.

  • Adverse/Side Effects:
      - Vincristine: Peripheral neuropathy without significant bone marrow suppression.
      - Paclitaxel: Dose-limiting toxicity including hypotension, angioedema, dyspnea, and bone marrow suppression.

  • Client Teaching: Notify the MD of any neurological symptoms or weakness.
      - Example: Vinca Alkaloids (Vincristine), Taxanes (Paclitaxel)

Hormonal Agents, Targeted Drugs, and Noncytotoxic Agents

Characteristics

  • General Info: Most lack the severe toxicities seen with cytotoxic agents (e.g., bone marrow suppression, alopecia, severe nausea, and vomiting).

  • Cell Cycle Phase: Most are non-specific across different cell phases.

  • Hormonal Agents:
      - Target primarily breast and prostate cancer.
      - Function by mimicking or blocking the action of endogenous hormones.

Breast Cancer

Treatment Strategies

  • Therapies Include:
      - Surgery
      - Radiation
      - Cytotoxic drugs
      - Hormonal agents

  • Major Groups of Hormonal Agents:
      - Antiestrogens: Block estrogen receptors.
      - Aromatase Inhibitors: Block estrogen synthesis; useful for hormone receptor-positive cancers.

Breast Cancer Medications

Antiestrogens

Tamoxifen

  • Mechanism of Action: Blocks estrogen from binding to cancer cells.

  • Indications: Approved for established breast cancer and high-risk primary prevention.

  • Adverse Effects: Risk of endometrial cancer, thromboembolism.

  • Client Education:
      - Administer consistently each day, typically for 5-10 years.

  • Example: Tamoxifen (Nolvadex).

Aromatase Inhibitors

Mechanism of Action

  • Action: Lowers estrogen levels by inhibiting aromatase enzymes.

  • Indications: Intended for postmenopausal women with hormone-positive breast cancer.

  • Adverse Effects: Joint/muscle pain, hot flashes, osteoporosis, fatigue, vaginal dryness.

  • Client Education:
      - Administer consistently each day, regular Dexa scans recommended, and increase calcium and vitamin D intake.

  • Example: Anastrozole (Arimidex).

Prostate Cancer Treatments

Overview

  • Commonality: Leading cause of cancer among men in the US.

  • Standard Treatment: Androgen Deprivation Therapy (ADT).

  • Types of Agents: Gonadotropin-Releasing Hormone (GnRH) Agonists.

  • Mechanism of Action: Risk of initial testosterone surge followed by suppression of production by the testes.

  • Indications: Specifically for prostate cancer treatment.

  • Adverse Effects: Well-tolerated in most cases but may include hot flashes, reduced libido, erectile dysfunction (ED), gynecomastia, and loss of muscle/bone mass.

  • Client Education: Co-treatment with an androgen receptor blocker (e.g., Flutamide) is advised; potential for fetal harm noted.

  • Example: Leuprolide (Lupron).

Angiogenesis Inhibitors

Mechanisms and Side Effects

  • Mechanism of Action: Prevent growth of new blood vessels needed for tumor sustenance.

  • Indications: Applicable to a diverse range of tumors.

  • Adverse Effects:
      - Risk of hemorrhage, arterial clots leading to stroke or heart attacks, hypertension, impaired wound healing.
      - Risk of reversible posterior leukoencephalopathy syndrome.
      - Possible proteinuria.

  • Client Education: Regular monitoring of side effects is essential.

  • Examples: Bevacizumab (Avastin), Ramucirumab (Cyramza), Sunitinib (Sutent).

Antiemetics

Overview of Nausea and Vomiting

  • Definitions:
      - Nausea: Unpleasant sensation leading to the urge to vomit.
      - Vomiting: Forceful expulsion of gastric contents (emesis).

  • Causes of Nausea and Vomiting: Potential causes include:
      - Morning sickness during pregnancy
      - Gastroenteritis
      - Motion sickness
      - Food poisoning
      - Medication side effects (especially chemotherapy).
      - GERD and ulcers.

Mechanism of Vomiting

Process Description

Involved Systems

  • Cerebral Cortex

  • Limbic System

  • Vomiting Center: Primarily located in the medulla and integrated with GI tract signals.

Physiological Actions:

  • Stomach relaxes.

  • Increased pyloric tone.

  • Decreased lower esophageal sphincter tone.

  • Glottis and vocal cords close.

  • Soft palate rises.

  • Contracting abdominal wall and diaphragm.

  • Activation of the chemoreceptor trigger zone (CTZ).

Antiemetics Overview

Anticholinergics

Mechanism of Action

  • Action: Block ACh receptors in the vestibular center and brain to inhibit nausea-inducing stimuli to the CTZ and vomiting center.

  • Administration Instructions:
      - Attach only one transdermal system at a time.
      - Do not cut patches and apply to a hairless area behind the ear.
      - Monitor for mental/physical impairment while on this medication.

  • Examples:
      - Scopolamine.

Antihistamines

Mechanism of Action

  • Action: Block H1 receptors in the vestibular center and may also inhibit ACh.

  • Specific Considerations: Contraindicated in glaucoma or enlarged prostate. Dosage recommendations indicate starting one hour before travel.

  • Examples: Meclizine.

Dopamine Antagonists

Mechanism of Action

  • Action: Block dopamine in the CTZ and may calm the central nervous system.

  • Client Teaching:
      - Avoid alcohol and other CNS depressants while taking this medication.
      - Watch for urine discoloration and increased sensitivity to light.

  • Examples: Prochlorperazine.

Prokinetics

Mechanism of Action

  • Action: Block dopamine and sensitize tissues to ACh, promoting gastrointestinal peristalsis.

  • Client Teaching: Report unusual movements (such as lip smacking and shaking) to healthcare provider.

  • Examples: Metoclopramide (Reglan).

Serotonin (5-HT3) Receptor Antagonists

Mechanism of Action

  • Action: Block serotonin receptors in the GI tract, CTZ, and vomiting center.

  • Warnings: Risk of serotonin syndrome when combined with other serotonin antagonists.

  • Adverse Effects: May include headaches, drowsiness, and QT prolongation.

  • Examples: Ondansetron.

Neurokinin Receptor Antagonists

Mechanism of Action

  • Action: Inhibit substance-P neurokinin receptors in the brainstem.

  • Client Teaching: Patients on warfarin should monitor their INR levels closely. Utilize backup contraception when on oral contraceptives.

  • Examples: Aprepitant, Fosaprepitant, Rolapitant.

Tetrahydrocannabinoids (THC)

Mechanism of Action

  • Action: Alters mood and perception; may relieve nausea and stimulate appetite.

  • Administration Considerations: Recognized as a controlled substance due to its potential for abuse.

  • Client Teaching: Patients should avoid driving or operating machinery.

  • Examples: Dronabinol.

Herbal and Vitamin Supplements

Examples

  • Ginger: Traditional antiemetic believed to block specific receptors.

  • Peppermint: Used for its soothing effects.

  • Pyridoxine (Vitamin B6): Recommended for pregnancy-related nausea.

Case Scenarios and Questions

Example Scenarios

  1. A patient develops severe nausea and vomiting from chemotherapy. Causes could include:
       - A. Stimulation of the chemoreceptor trigger zone
       - B. Anxiety and anticipatory grieving
       - C. Increased peristalsis of the gastrointestinal tract
       - D. Injury of the epithelial lining of the esophagus and stomach

  2. When receiving chemotherapy, a male patient’s laboratory value may lead to treatment being withheld if:
       - A. Platelet count is 157,000/mm³
       - B. Neutrophil count is 375/mm³
       - C. Hemoglobin is 12.2 g/dL
       - D. Partial thromboplastin time is 35 seconds

  3. Patient inquiries about minimizing chemotherapy side effects and appropriate advice includes:
       - A. “Avoid contact with people who are ill.”
       - B. “Take antiemetics immediately after chemotherapy.”
       - C. “Treat fevers immediately with ibuprofen.”
       - D. “Use a firm-bristled toothbrush to stimulate gums.”

  4. In a patient prescribed cyclophosphamide (Cytoxan), nursing education will include:
       - A. Monitoring for hepatotoxicity
       - B. Alopecia as a rare side effect
       - C. Taking it on an empty stomach
       - D. Increasing fluid intake to prevent kidney damage

  5. About vincristine (Oncovin) therapy, nurses will educate about:
       - A. Expectation of peripheral neuropathies
       - B. Expectation of hair loss
       - C. Expectation of nausea and vomiting
       - D. Expectation of bone marrow suppression