Chemotherapy Agents

Jeremy S. Heiner, Ed.D., CRNA

Objectives

• Discuss the major chemotherapeutic agent classes.

• Identify effects of chemotherapeutic agents on body systems.

• Review anesthesia considerations.

• Discuss the effects of surgery and anesthesia on cancer recurrence and the immune system.

Cancer Incidence

• 2012 = 1,640,000 new cases/ 577,000 deaths.

• 2nd most common cause of death.

• Breast, prostate, lung, & colorectal cancers.

Chemotherapeutic Agents

• Interfere with cell replication and DNA synthesis.

• Target cells that rapidly replicate.

• Damage healthy cells.

Cytotoxic Drug Sites of Action During Cell

Division

Alkylating Agents

• Essentially these drugs chemically modify the cells DNA.

• Transfer of alkyl group within DNA from one molecule to another.

• Bind to DNA and inhibit both normal and cancer cell DNA processing.

• Intracellular imbalance and cell death.

• Inhibit protein synthesis.

Antimetabolites

• Substitute chemicals that are structurally similar to normal metabolites.

• Interfere with cell growth and division by preventing normal DNA replication.

• Can halt cell growth and cell division.

Antitumor Antibiotics

• Inhibit DNA and RNA synthesis.• Causes structural distortion of

DNA/RNA molecule.

• Block DNA transcription and replication. • Inhibits enzymes that wind and

unwind DNA.

• Damages DNA and cell membranes.• Iron-mediated free oxygen

molecules.

Vinca Alkaloids & Taxanes

• Interfere with the structural components important for cell replication.

• Interacts with and modifies microtubular proteins: • Alters cell division and cytokinesis• Alter microtubule function causing apoptosis

(programmed cell death)

• Made from the sap of the Madagascar Periwinkle.

Miscellaneous Agents

• Biological response modifiers• Interferon-alpha• Monoclonal antibodies

• Hormone therapy

• Mustard gas

• Other chemotherapeutic agents alter cell replication and DNA synthesis.

Cancer Premedications

• Antiemetic medications• Combination therapy

• Histamine blocking agents

• Analgesics• Cancer is associated with significant pain

• Anxiolytics• Psychological aspect of cancer

Toxic Effects of Chemotherapeutic Agents

• Type of drug

• Cumulative dose

• Dosing schedule

• Side effects vary

Myelosuppresion

• Bone marrow suppression

• Anemia

• Leukopenia

• Thrombocytopenia

• Coagulation disorders – anthracyclines & antitumor antibiotics

Central Nervous System

• Seizures – Busulfan

• Peripheral neuropathies – Vinca alkaloids; Taxanes; Alkylating agents

• Loss of deep tendon reflex – Vinca alkaloids

• Extremity weakness – Vinca alkaloids

• Vocal cord paralysis – Vinca alkaloids

• Loss of extraocular muscle function – Vinca alkaloids

Cardiovascular System• Anthracyline

antibiotics can cause cardiotoxicity.

• Risk factors for cardiac dysfunction:• Radiation of mediastinum or left chest

• Age

• Preexisting cardiac disease

• Left ventricular ejection fraction <50%

• Type of surgery

Cardiovascular System

• Signs and symptoms of cardiac damage:• Abnormal ECG findings, ST-T wave changes, QT interval

prolongation, dysrhythmias• Thrombosis, myocarditis, pericarditis, myocardial infarction,

cardiomyopathy

• Chronic manifestations of progressive cardiotoxicity:• Tachycardia • Blood pressure changes• Ventricular dilation• Exercise intolerance• Pulmonary and venous congestion• Poor perfusion

Pulmonary System

• Damage from direct lung injury or indirectly from inflammatory process.

• Bleomycin most associated with pulmonary toxicity.

• Risk factors for pulmonary dysfunction:• Age over 70• Existing pulmonary disease (COPD)• Smoking history• Genetic predisposition• Thoracic radiation therapy

Pulmonary System

• Signs and symptoms of pulmonary dysfunction:• Early inflammatory interstitial

pneumonitis• Acute noncardiogenic pulmonary

edema• Bronchospasm• Pleural effusion• Dyspnea• Cough• Tachypnea• Rales and/or wheezing• Fever

Renal System

• Acute or chronic renal failure.

• Damage to glomerular filtration, proximal tubular function, and distal tubular function.• Cisplatin, methotrexate, & ifosfamide

• Nonsteroidal anti-inflammatory drugs.

• Avoid or decrease the dose of medications that require renal clearance.

Renal System

• Risk factors for renal dysfunction:• Previous renal dysfunction • Decreased renal perfusion

• Signs and symptoms of renal dysfunciton:• Increased serum creatinine and decreased urine

creatinine clearance• Uremia• Electrolyte abnormalities • Filtration abnormalities

Hepatic System

• Signs and symptoms of hepatic dysfunction:• Elevated liver enzymes• Cirrhosis• Coagulopathies• Jaundice • Dark amber urine

• Methotrexate may induce hepatic cirrhosis and fibrosis.

• Anesthetic medications may have prolonged effect.

Gastrointestinal System

• GI mucosa sensitive to cytotoxic agents.

• Increased risk for aspiration.

• Electrolyte imbalances, dehydration, weight loss, and malnutrition.

• Signs and symptoms of GI dysfunction:• Oral mucositis • Decreased appetite• Diarrhea • Nausea and vomiting

Anesthetic Considerations

• Comprehensive preoperative history and physical examination.

• Consult with cancer physician.

• Consider corticosteroid supplementation.

• Aspiration prophylaxis.

• Patients may be taking antiemetic.

• Patients are at increased risk of sepsis.

• Prolonged duration of muscle relaxants.

• Neuromuscular blockade monitoring.

Labs and Tests

• Consider electrolytes, blood count, coagulation studies, cardiac enzymes, renal function, urine creatinine clearance, and liver function tests.

• Chest radiograph.

• Obtain ECG, cardiac echocardiogram, and may consider ejection fraction.

• PFT’s as needed.

• Blood products.

Lines and Monitoring

• IV access may be difficult

• Arterial line

• Central line

• Careful management of intravenous fluids

• TEE

• Temperature

Airway Considerations

• Range of motion

• Hoarseness

• Oral inflammation and ulceration

• Existing airway tumors in or around airway

• Auscultate

• Avoid high FiO2 (bleomycin)

• Post-operative Ventilation

Anesthetic Considerations

• Document existing neuropathies

• Chronic SNS stimulation• Consider non-adrenergic inatropes• Avoid ketamine

• Avoid excessive fluid administration

• Avoid NSAID’s

• Avoid Sevoflurane if evidence of renal disease

• Possible P-450 enzyme induction

• Pain management

Surgery and Anesthesia Effects on Cancer

Recurrence

• Tumor metastases

• Surgery suppresses immune system

• Anesthesia can suppress immune system

• Regional anesthesia

Anesthetic Best Practice for Patients

with Cancer• Cancer pain requires treatment.

• Currently no evidence to justify altering anesthesia techniques.

• Focus should be on good analgesia, decreasing surgical stress, and reducing inflammation.

Questions?