ASTRO-RTOG 1012 symptom managementpresentation 2014.pptx

Manuka honey to prevent radiation esophagitis

1. Randomized Phase II Trial of Best Supportive Care, Manuka Honey Liquid and Manuka Honey Lozenges for Prevention of Radiation Esophagitis d uring Chemotherapy and Radiotherapy for Lung Cancer . Lawrence B. Berk, MD , PhD , Snehal Deshmukh , MS, Shannon Fogh , MD, Kevin Roof, MD, Sherif Yacoub , MD, PhD, Thomas Gergel , MD, Kevin Stephans , MD, Andreas Rimner , MD, Albert DeNittis MD MS, John Pablo, MD, Justin Rineer , MD, Arnab Chakravarti , MD, Deborah Bruner , PhD, RN ASTRO September 2014

2. Rationale Folk literature on using honey to heal wounds Preclinical data showing effects of honey on inflammatory cytokines and stimulation of wound repair Four published clinical trials showing clinical and statistical efficacy of honey for prevention of radiation oropharyngeal mucositis . The trials used local honeys. Biswal et al., 2003, 40 patients, Malaysia Motallebnejad et al., 2008, 40 patients, Iran Rashad et al., 2009, 40 patients, Egypt Khanal et al., 2010 40 patients, Nepal This project was supported by RTOG grant U10 CA21661, and CCOP grant U10 CA37422 from the National Cancer Institute (NCI )

3. Manuka Honey Chosen for this Trial Honey from New Zealand Regulated by the Active Manuka Honey Association Controlled for anti-bacterial activity (Unique Manuka Factor, UMF) Extensive basic studies on its contents and activity Extensive clinical studies on its use in wound healing and is a commercial product for wound healing

4. Clinical Design Chose to evaluate radiation esophagitis during chemoradiation therapy Defined parameters expected to induce clinically significant esophagitis Chemotherapy and radiation therapy for small cell or non-small cell lung cancer with once a day treatment At least 5 cm of the esophagus receiving within 69 Gy isodose No prior chemotherapy for the lung cancer IMRT or 3D planning allowed Receiving at least 60 Gy total dose

5. Schema

6. Endpoints Primary Endpoint – swallowing pain on an 11 point scale (Numerical Pain Rating Scale, NPRS) at 4 weeks of RT Secondary Endpoints: overall severity of esophagitis during treatment including all times of NRPS assessment (weekly during treatment and 12 weeks from the start of treatment ) EORTC QLQ-30 with pain subscale at baseline and at 4 and 12 weeks from start of treatment swallowing diary daily during treatment and at 12 weeks including dysphagia Patient weight loss from baseline to 4 weeks Opioid use CTCAE V4 adverse events PRO-CTCAE pilot study

7. Accrual The trial opened to accrual on February 28, 2012. Due to distribution issues, it temporarily closed to accrual on April 10, 2012 to reopen on April 23, 2012. Due to honey-related issues, it closed on July 26, 2012 and reopened on April 4, 2013. The study reached its target accrual and closed on October 15, 2013 with 163 patients enrolled. Monthly accrual was higher than projected (8.3 vs. 5 patients per month).

8. Eligibility

9. Worst AEs per Patient XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

10. NPRS Compliance Reasons for Non-Compliance: Consent withdrawal (11% by 12 weeks) Other Not reported No protocol treatment Illness Unable to contact patient

11. Primary Endpoint: Change in NPRS Score at 4 Weeks XXXXXXXXXXXXX p=0.92 n=41 n=40 n=38

12. Longitudinal Change in NPRS Scores XXXXXXXXXXXXXXX

13. Discussion Two subsequent trials showed that Manuka honey is inactive for mucositis Hawley et al., 2013, 81 patients, Canada Bardy et al., 2012, 131 patients, England One subsequent trial showed local honey is active for mucositis Raeesi et al., 2014, 75 pts (honey vs. honey and coffee vs. betamethasone), Iran

14. Limitations/Conclusions Testing natural products introduces many confounding variables and issues when compared to standard drug protocols. In this trial m anuka honey had no significant effect on preventing pain due to radiation esophagitis A trial with a honey active in other trials is needed for confirmation of their results