PMID- 30833486 OWN - NLM STAT- MEDLINE DCOM- 20200727 LR - 20211204 IS - 1549-490X (Electronic) IS - 1083-7159 (Print) IS - 1083-7159 (Linking) VI - 24 IP - 9 DP - 2019 Sep TI - Evaluation of Miracle Mouthwash plus Hydrocortisone Versus Prednisolone Mouth Rinses as Prophylaxis for Everolimus-Associated Stomatitis: A Randomized Phase II Study. PG - 1153-1158 LID - 10.1634/theoncologist.2018-0340 [doi] AB - BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitor-associated stomatitis (mIAS) is a frequent adverse event (AE) associated with mTOR inhibitor therapy and can impact treatment adherence. The objectives are to evaluate two steroid-based mouthrinses for preventing/ameliorating mIAS in patients with metastatic breast cancer (MBC) treated with everolimus. MATERIALS AND METHODS: This prospective, randomized phase II study enrolled 100 postmenopausal patients with hormone receptor-positive MBC within the US Oncology Network who were initiating therapy with an aromatase inhibitor + everolimus (AIE; 10 mg/day). Patients were randomized to prophylactic therapy with one of two oral rinses (Arm 1: Miracle Mouthwash [MMW] 480 mL recipe: 320 mL oral Benadryl [diphenhydramine; Johnson & Johnson, New Brunswick, NJ, USA], 2 g tetracycline, 80 mg hydrocortisone, 40 mL nystatin suspension, water; or Arm 2: prednisolone [P] 15 mg/5 mL oral solution, 1.8% alcohol). Patients were instructed to swish/expectorate 10 mL of the assigned rinse for 1-2 minutes four times daily starting with day 1 of AIE treatment, for the first 12 weeks. RESULTS: A total of 100 patients received treatment (49 MMW; 51 P). The incidence of stomatitis/oral AEs during the first 12 weeks was 35% (n = 17/49) and 37% (19/51) in the MMW and P arms, respectively. The incidence of grade 2 oral AEs was 14% (7/49) and 12% (6/51) with MMW or P, respectively. There were two grade 3 oral AEs (MMW arm) and no grade 4 events. There was one everolimus dose reduction (MMW) and six dose delays (four MMW, two P) and one dose reduction + delay (MMW) during the first 12 weeks of treatment. No patients stopped steroid mouthwash therapy because of rinse-related toxicity. CONCLUSION: Prophylactic use of steroid-containing oral rinses can prevent/ameliorate mIAS in patients with MBC treated with AIE. MMW + hydrocortisone is an affordable option, as is dexamethasone oral rinse. IMPLICATIONS FOR PRACTICE: This prospective phase-II study showed that two steroid-containing mouthrinses substantially reduced incidences of all-grade and grade >/=2 stomatitis and related oral adverse events (AEs), and the number of everolimus dose-delays and/or dose-reduction in metastatic breast cancer (MBC) patients receiving everolimus treatment plus an aromatase inhibitor. Both oral rinses were well tolerated and demonstrated similar efficacy. Prophylactic use of steroid mouth rinse provides a cost-effective option that substantially decreases the incidence and severity of mammalian target of rapamycin (mTOR) inhibitor-associated stomatitis and related oral AEs as well as the need for dose modification in MBC patients undergoing treatment with an mTOR inhibitor. CI - (c) AlphaMed Press 2019. FAU - Jones, Vicky E AU - Jones VE AD - US Oncology Research, Inc., The Woodlands, Texas, USA. AD - Yakima Valley Memorial Hospital/North Star Lodge, Yakima, Washington, USA. FAU - McIntyre, Kristi J AU - McIntyre KJ AD - US Oncology Research, Inc., The Woodlands, Texas, USA. AD - Texas Oncology, Dallas, Texas, USA. FAU - Paul, Devchand AU - Paul D AD - US Oncology Research, Inc., The Woodlands, Texas, USA. AD - Rocky Mountain Cancer Center, Denver, Colorado, USA. FAU - Wilks, Sharon T AU - Wilks ST AD - US Oncology Research, Inc., The Woodlands, Texas, USA. AD - Texas Oncology, San Antonio, Texas, USA. FAU - Ondreyco, Sharon M AU - Ondreyco SM AD - US Oncology Research, Inc., The Woodlands, Texas, USA. AD - Arizona Oncology, Glendale, Arizona, USA. FAU - Sedlacek, Scot AU - Sedlacek S AD - US Oncology Research, Inc., The Woodlands, Texas, USA. AD - Rocky Mountain Cancer Center, Denver, Colorado, USA. FAU - Melnyk, Anton AU - Melnyk A AD - US Oncology Research, Inc., The Woodlands, Texas, USA. AD - Texas Oncology, Abilene, Texas, USA. FAU - Oommen, Sanjay P AU - Oommen SP AD - US Oncology Research, Inc., The Woodlands, Texas, USA. AD - Texas Oncology, Fort Worth, Texas, USA. FAU - Wang, Yunfei AU - Wang Y AD - US Oncology Research, Inc., The Woodlands, Texas, USA. AD - McKesson Specialty Health, Inc., The Woodlands, Texas, USA. FAU - Peck, Susan R AU - Peck SR AD - McKesson Specialty Health, Inc., The Woodlands, Texas, USA. FAU - O'Shaughnessy, Joyce A AU - O'Shaughnessy JA AD - US Oncology Research, Inc., The Woodlands, Texas, USA joyce.oshaughnessy@usoncology.com. AD - Texas Oncology/Baylor University Medical Center, Dallas, Texas, USA. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20190304 PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antineoplastic Agents) RN - 0 (Mouthwashes) RN - 9HW64Q8G6G (Everolimus) RN - 9PHQ9Y1OLM (Prednisolone) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - WI4X0X7BPJ (Hydrocortisone) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Anti-Inflammatory Agents/administration & dosage MH - Antineoplastic Agents/adverse effects/therapeutic use MH - Breast Neoplasms/*drug therapy/pathology MH - Everolimus/*adverse effects/therapeutic use MH - Female MH - Humans MH - Hydrocortisone/*administration & dosage MH - Middle Aged MH - Mouthwashes/*administration & dosage MH - Prednisolone/*administration & dosage MH - Prospective Studies MH - Stomatitis/chemically induced/drug therapy/pathology/*prevention & control MH - TOR Serine-Threonine Kinases/*antagonists & inhibitors PMC - PMC6738305 OTO - NOTNLM OT - Aromatase inhibitor OT - Everolimus OT - Mouthwash OT - Prednisolone OT - Stomatitis COIS- Disclosures of potential conflicts of interest may be found at the end of this article. EDAT- 2019/03/06 06:00 MHDA- 2020/07/28 06:00 PMCR- 2019/09/01 CRDT- 2019/03/06 06:00 PHST- 2018/06/13 00:00 [received] PHST- 2018/12/21 00:00 [accepted] PHST- 2019/03/06 06:00 [pubmed] PHST- 2020/07/28 06:00 [medline] PHST- 2019/03/06 06:00 [entrez] PHST- 2019/09/01 00:00 [pmc-release] AID - theoncologist.2018-0340 [pii] AID - ONCO12855 [pii] AID - 10.1634/theoncologist.2018-0340 [doi] PST - ppublish SO - Oncologist. 2019 Sep;24(9):1153-1158. doi: 10.1634/theoncologist.2018-0340. Epub 2019 Mar 4.