1. Chemotherapy Agents Jeremy S. Heiner, Ed.D., CRNA

2. 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.

3. Cancer Incidence 2012 = 1,640,000 new cases/ 577,000 deaths. 2 nd most common cause of death. Breast, prostate, lung, & colorectal cancers.

4. Chemotherapeutic Agents Interfere with cell replication and DNA synthesis. Target cells that rapidly replicate. Damage healthy cells.

5. Cytotoxic Drug Classes Alkylating agents Antimetabolites Antitumor antibiotics Vinca Alkaloids & Taxanes Miscellaneous

7. Cytotoxic Drug Sites of Action During Cell Division

8. 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.

9. 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.

10. 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.

11. 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.

12. Miscellaneous Agents Biological response modifiers Interferon-alpha Monoclonal antibodies Hormone therapy Mustard gas Other chemotherapeutic agents alter cell replication and DNA synthesis.

13. Cancer Premedications Antiemetic medications Combination therapy Histamine blocking agents Analgesics Cancer is associated with significant pain Anxiolytics Psychological aspect of cancer

14. Toxic Effects of Chemotherapeutic Agents Type of drug Cumulative dose Dosing schedule Side effects vary

16. Myelosuppresion Bone marrow suppression Anemia Leukopenia Thrombocytopenia Coagulation disorders – anthracyclines & antitumor antibiotics

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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.

23. 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

24. 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.

25. 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

26. 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.

27. 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.

28. Lines and Monitoring IV access may be difficult Arterial line Central line Careful management of intravenous fluids TEE Temperature

29. 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

30. 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

31. Surgery and Anesthesia Effects on Cancer Recurrence Tumor metastases Surgery suppresses immune system Anesthesia can suppress immune system Regional anesthesia

32. 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.

33. Questions?