1. Managing Chemotherapy Toxicities in GI Cancers September 30, 2008 Christine Brezden-Masley, MD PhD FRCPC

2. GI Chemotherapy Management | Sept 30, 2008 | 2 C. Brezden Objectives To understand toxicities from –colorectal cancer therapy –gastric cancer therapy To manage toxicities from –colorectal cancer therapy –gastric cancer therapy

3. GI Chemotherapy Management | Sept 30, 2008 | 3 C. Brezden Colorectal Cancer Adjuvant colorectal cancer –FOLFOX –Xeloda –Clinical trial: CRC2 – Stage 3 CRC: FOLFOX +/- Cetuximab (for RAS wt patients) CRC3 – Stage 2 CRC: 18q deletion: FOLFOX +/- Avastin CRC4 – Stage 2-3 Rectal cancer: FOLFOX +/- Avastin

4. GI Chemotherapy Management | Sept 30, 2008 | 4 C. Brezden FOLFOX Dose-limiting cold-induced sensory peripheral neuropathy –Ask patients if are able to button shirt and write If so, but have tingling >14 days (into next cycle) then decrease dose of oxaliplatin 85 mg/m 2 to 65 mg/m 2 If pain and significant paresthesia, cannot button shirt, cannot write – discontinue oxaliplatin and continue with FUFA –Any prevention studies for neuropathy?

5. GI Chemotherapy Management | Sept 30, 2008 | 5 C. Brezden CalMag Infusions

6. GI Chemotherapy Management | Sept 30, 2008 | 6 C. Brezden 2008 ASCO

7. GI Chemotherapy Management | Sept 30, 2008 | 7 C. Brezden 2008 ASCO

8. GI Chemotherapy Management | Sept 30, 2008 | 8 C. Brezden 2008 ASCO

9. GI Chemotherapy Management | Sept 30, 2008 | 9 C. Brezden 2008 ASCO

10. GI Chemotherapy Management | Sept 30, 2008 | 10 C. Brezden 2008 ASCO

11. GI Chemotherapy Management | Sept 30, 2008 | 11 C. Brezden 2008 ASCO

12. GI Chemotherapy Management | Sept 30, 2008 | 12 C. Brezden 2008 ASCO

13. GI Chemotherapy Management | Sept 30, 2008 | 13 C. Brezden 2008 ASCO

14. GI Chemotherapy Management | Sept 30, 2008 | 14 C. Brezden 2008 ASCO

15. GI Chemotherapy Management | Sept 30, 2008 | 15 C. Brezden 2008 ASCO

16. GI Chemotherapy Management | Sept 30, 2008 | 16 C. Brezden 2008 ASCO

17. GI Chemotherapy Management | Sept 30, 2008 | 17 C. Brezden 2008 ASCO

18. GI Chemotherapy Management | Sept 30, 2008 | 18 C. Brezden 2008 ASCO

19. GI Chemotherapy Management | Sept 30, 2008 | 19 C. Brezden 2008 ASCO

20. GI Chemotherapy Management | Sept 30, 2008 | 20 C. Brezden 2008 ASCO

21. GI Chemotherapy Management | Sept 30, 2008 | 21 C. Brezden 2008 ASCO

22. GI Chemotherapy Management | Sept 30, 2008 | 22 C. Brezden 2008 ASCO

23. GI Chemotherapy Management | Sept 30, 2008 | 23 C. Brezden 2008 ASCO

24. GI Chemotherapy Management | Sept 30, 2008 | 24 C. Brezden 2008 ASCO

25. GI Chemotherapy Management | Sept 30, 2008 | 25 C. Brezden Neuropathy CalMag –2-3 tablets per day without food Stay warm Do not drink cold fluids

26. GI Chemotherapy Management | Sept 30, 2008 | 26 C. Brezden Nausea and Vomiting FOLFOX –Hesketh 4 FOLFIRI –Hesketh 4 ECF/ECX –Hesketh 5 Xeloda (Capecitabine) –Hesketh 2

27. GI Chemotherapy Management | Sept 30, 2008 | 27 C. Brezden

28. GI Chemotherapy Management | Sept 30, 2008 | 28 C. Brezden Nausea and Vomiting Immediate –Zofran 8mg po BID –Decadron 8 mg po BID X 3 days with chemotherapy Delayed –Stemetil –Maxeran

29. GI Chemotherapy Management | Sept 30, 2008 | 29 C. Brezden Delayed N/V IV hydration at home –CCAC daily IV hydration with NS 600ml/day Marinol/Nabilone (cannabinoid) Haldol Aprepitant –Cost Zyprexa (olanzapine)

30. GI Chemotherapy Management | Sept 30, 2008 | 30 C. Brezden Diarrhea FOLFOX FOLFIRI –Imodium –Loperamide NO MAXIMUM for chemotherapy-induced diarrhea Ensure no C.Difficile (ischemic gut) –Somatostatin (100 mg sc x1)

31. GI Chemotherapy Management | Sept 30, 2008 | 31 C. Brezden FOLFIRI Immediate diarrhea (during infusion) –SN38 active metabolite –Cholinergic response Treatment with Atropine 0.2 mg sc x1 Morphine (cramping)

32. GI Chemotherapy Management | Sept 30, 2008 | 32 C. Brezden Myelosuppression No role for primary prevention of GCSF –FOLFIRI>FOLFOX –ECF/ECX For CURATIVE intent –Can treat with GCSF – funding an issue –If private insurance – can use in advanced care to push doses

33. GI Chemotherapy Management | Sept 30, 2008 | 33 C. Brezden Myelosuppression If febrile neutropenia –Not difficult for Section 8 to fund FOLFOX and Gemcitabine –Thrombocytopenia If platelets <85 should dose-reduce Educate patient about bleeding risk Anemia –Check for Fe stores – supplement –Role for ESAs?

34. GI Chemotherapy Management | Sept 30, 2008 | 34 C. Brezden XELODA Hand-Foot Syndrome –Keep hands and feet moist with Udder cream –May reduce dose if continues (blistering and desquamation and pain) Diarrhea Mucositis

35. GI Chemotherapy Management | Sept 30, 2008 | 35 C. Brezden Mucositis Good oral hygeine critical –Baking soda rinses – ½ teaspoon of baking soda in half glass of water daily 2-3x –If severe neutropenia – than mucositis usually occurs Nystatin (Nilstat) 500,000 Units po q4-6 hours (swish and swallow) Tantum (ODB) Butlers/Blacksteins mouth wash

36. GI Chemotherapy Management | Sept 30, 2008 | 36 C. Brezden DPD Dihydropyrimidine dehydrogenase (DPD) –Catabolic pathway of 5-FU Responsible for 85% of degradation of 5-FU –5-FU5-FUTP5-FdUMP (ACTIVE form) DPD deficiency –3-5% population (polymorphisms as high as 8%) –Autosomal recessive

37. GI Chemotherapy Management | Sept 30, 2008 | 37 C. Brezden DPD Deficiency DPD Deficiency Syndrome –Grade 4 neutropenia –Severe/fatal diarrhea –Mucositis/stomatitis –Rash Can happen after 1 st or 2 nd dose of 5-FU Treatment –Supportive care

38. GI Chemotherapy Management | Sept 30, 2008 | 38 C. Brezden Clinical Pearls Shape your practice – you’re the boss Do not need to examine patient at each chemotherapy session – but need to –MONITOR ALL BLOODWORK –MONITOR SIDE-EFFECTS –ASK PATIENT HOW THEY’RE DOING FATIGUE/ENERGY APPETITE MOOD

39. GI Chemotherapy Management | Sept 30, 2008 | 39 C. Brezden CLINICAL PEARLS NEED TO ASSESS PATIENT –Pain –New symptoms/signs Dehydration Neurologic Major organ involvement –Respiratory (r/o PE) –Cardiac (electrolyte disturbances) –Renal –Hepatic (Ascites)

40. GI Chemotherapy Management | Sept 30, 2008 | 40 C. Brezden Thanks Questions? brezdenc@smh.toronto.on.ca