Managing Gastrointestinal Side Effects of Targeted Therapies

1. Managing Gastrointestinal Side Effects of Targeted Therapies Amy Goodrich, MSN, NP-AC The Johns Hopkins Kimmel Cancer Center, Baltimore, MD

2. General Concepts of GI Toxicity in Cancer Patients • Chronic GI side effects commonly cause significant morbidity and reduced quality of life in cancer patients • GI side effects commonly overlooked due to focus on disease status • GI symptoms can often be alleviated or eliminated

3. GI Toxicity in Targeted Therapies • Spectrum of GI toxicity and causes often poorly defined • Normal cells of the GI system, including liver, may express molecular targets • Hepatic or GI adverse events may be alternate markers of treatment efficacy of some targeted agents • Extensive Drug-Drug interactions • GI toxicity and management varies from single agent to combination therapy

4. Diarrhea Grading

5. Diarrhea • Major cause of treatment discontinuation • Common DLT

6. Diarrhea • EGFR overexpressed in normal GI mucosa- possibly due to increased chloride secretion leading to secretory diarrhea • Imatinib- dose related • Bortezomib- watery diarrhea with abdominal pain and cramps • Temsiroloimus- Immunosupressive or antimicrobial effect could alter normal bowel flora leading to mucoid feces and colitis • Gefitinib- Inflammatory mediators in response to cell immunity activation

7. Diarrhea Management • Hydration • Electrolyte management • BRAT diet • Culture • Loperamide • Octreotide • Antibiotics if prolonged or w/neutropenia • Low dose aspirin with gefitinib

8. Nausea and Vomiting Grading

9. Nausea and Vomiting

10. Nausea and Vomiting • Cited as the most concerning symptom of antineoplastic therapy • Significantly impacts quality of life • Affected by: specific agent, dose, schedule and route, patient-related variables • Multifactorial • Most Targeted Therapies have low to minimal emetogenic potential • Is it time for a revised CTCAE to reflect long term therapy vs. traditional chemo cycles?

11. Management of Nausea and Vomiting • Follow guidelines for prevention and treatment • Hydration • Dietary changes- small frequent meals, bland foods, full liquids, room temperature foods • Nonpharmacologic- acupuncture, guided imagery, music therapy, progressive muscle relaxation, many others

12. Recommended Antiemesis Prophylaxis

13. Oral Mucositis Grading

14. Stomatitis/Mucocitis

15. Oral Mucositis Management • Oral care- Saline rinses, soft tooth brushes • Hydration • Dietary modifications- Soft diet, bland foods • Analgesics- topical and systemic • Consider anti-infectives

16. Dyspepsia Grading

17. Dyspepsia

18. Dyspepsia Management • Pharmacologic treatment, watch for drug-drug interactions • Dietary changes- avoid spicy or fatty foods, no eating within 2 hours of bedtime

19. Liver Function Abnormality Grading

20. Liver Function Abnormalities

21. GI Emergencies

22. Conclusions • Targeted therapies carry high incidence of GI toxicity • Usually mild • Patient distress easily overlooked by providers • Chronic dosing of targeted therapies makes side effect control critical