1. Ginger for Chemotherapy-related Nausea in Cancer Patients Julie L. Ryan, PhD, MPH 1 C. Heckler, PhD 1, S.R. Dakhil, MD 2, J. Kirshner, MD 3, P.J. Flynn, MD 4, J.T. Hickok, MD, MPH 1, G.R. Morrow, PhD, MS 1 1 University of Rochester Medical Center, URCC CCOP, Rochester, NY; 2 Witchita CCOP, Witchita, KS; 3 HAOCNY CCOP, Syracuse, NY; 4 Metro-MN CCOP, St. Louis Park, MN Supported by NCI PHS grants U10CA37420 and 1R25CA10618

2. Chemotherapy-related Nausea Most severe & distressing chemotherapy-related side effects: –Nausea = #1 –Vomiting = #5 Nausea experienced by over 73% of cancer patients receiving chemotherapy. Onset: –Acute (0-24 hours after treatment) –Delayed (24-120 hours after treatment)

3. What is Nausea? A subjective and unobservable phenomenon Brain-Gut Connection Enteric nervous system (2 nd brain) Neurotransmitters in the gut: –Serotonin (5-HT 3 ) –Dopamine –Neurokinin Self assessment tools, such as diaries and visual analog scales, are gold standard for measuring nausea. http://www.thewholechild.us/integrative_/gut-brain.jpg

4. Why Ginger? Long history (~2500 years) of medicinal use –Headaches, acid indigestion, nausea, diarrhea, colds, arthritis, rheumatological conditions, muscular discomfort. North American Folklore –What your grandma always told you!! Potent anti-inflammatory Anti-spasmodic activity in the gut http://www.bonappetit.com/images/tips_tools_ingredients/i ngredients/ttar_ginger_v.jpg

5. Research on Ginger & Chemotherapy-related Nausea Effective –Pace et al (1986): N = 41 Two-arm, randomized, placebo-controlled; 500mg Ginger –Levine et al (2008): N = 28 Unblinded, three arm study (Protein with ginger) Ineffective –Zick et al (2008): N =162 Three-arm, randomized, placebo-controlled; 1.0g & 2.0g Ginger

6. Central Illinois CCOPGulf Coast MBCCOPNorth Shore University Hospital CCOP Columbia River CCOPHawaii MBCCOPNorthwest CCOP Columbus CCOPHematology-Oncology of CNY CCOPSoutheast Cancer Control Consortium Dayton Clinical Oncology ProgramKalamazoo CCOPUniversity of Illinois at Chicago MBCCOP Evanston CCOPKansas City CCOPUpstate Carolina CCOP Grand Rapids CCOPMarshfield Clinic Research Foundation CCOPVirginia Mason Research Center CCOP Greenville CCOPMetro-Minnesota CCOPWichita CCOP Nevada Cancer Research Foundation CCOP CCOPs URCC University of Rochester Cancer Center Community Clinical Oncology Research Base Map of Affiliates (2009)

7. Primary Objective To determine if ginger is more effective than placebo in controlling chemotherapy-related nausea on Day 1 of chemotherapy in patients receiving 5-HT 3 receptor antagonist antiemetics.

8. Eligibility Criteria Cancer patients who experienced nausea with any chemotherapy cycle. Patients scheduled for at least 3 additional chemotherapy cycles. Patients scheduled to receive 5-HT 3 receptor antagonist antiemetics on Day 1 of all chemotherapy cycles. Patients not taking warfarin (Coumadin®) or heparin.

9. Study Schema Placebo 0.5g Ginger 1.0g Ginger 1.5g Ginger

10. Study Schema

11. Key Points of Study All patients received 5-HT 3 receptor antagonist antiemetics (i.e., Zofran®, Kytril®, etc.) on Day 1 of all cycles. All patients took ginger or placebo for six days, starting three days before chemotherapy. Patients reported nausea four times daily (morning, afternoon, evening, night): 17 Not Nauseated Extremely Nauseated

12. Patient Descriptives  Total N = 644 cancer patients 90% female, 92% White, mean age = 53  Most common cancer types Breast (66%), alimentary (6.5%), lung (6.1%)  Previous Treatments 86% Surgery; 56% Chemotherapy; 7% Radiation  No exclusion based on chemotherapy regimen Both moderately & highly emetic regimens used.  No significant difference in drop-out rate between treatment arms. Overall = 15% 71% of patients completed all study cycles.

13. Results Day 1, Study Cycle 2Day 1, Study Cycle 3 M = Morning (6 hrs.); A = Afternoon (12 hrs.); E = Evening (18 hrs.); N = Night (24 hrs.) P=0.003 LessLess LessLess LessLess LessLess

14. No Significant Effect on Vomiting Time of Day -0.05 0.00 0.05 MAENMAEN Placebo0.5g Ginger1.0g Ginger1.5g Ginger Day 1, Study Cycle 2Day 1, Study Cycle 3 Time of Day Change in Proportion Vomited

15. Conclusions Ginger supplementation at daily dose of 0.5g-1.0g significantly aids in reduction of nausea on the first day of chemotherapy. Reduced nausea will lead to improved quality of life for cancer patients during chemotherapy.

16. Acknowledgements Gary R. Morrow, PhD, MS Joe Roscoe, PhD Jane Hickok, MD Charles Heckler, PhD Behavioral Medicine Unit Community Clinical Oncology Program Affiliates University of Rochester Medical Center & Wilmot Cancer Center National Cancer Institute