# Radiation Oncology/Supportive care/Oral mucositis

* Front Page: Radiation Oncology | RTOG Trials | Randomized Trials
Oral Mucositis Supportive Care

## Honey

* Egypt (2005-2006) -- chemo-RT +/- honey
** Randomized. 40 patients with H&N cancer, treated with chemo-RT with significant area of oral or oropharynx mucosa in treatment field. Arm 1) topical application of pure natural honey vs. Arm 2) no honey. Evaluated weekly, aerobic cultures and candida colonisation assessed
** 2008 PMID 18485252 -- "Honey as topical prophylaxis against radiochemotherapy-induced mucositis in head and neck cancer." (Rashad UM, J Laryngol Otol. 2008 May 19:1-6. [Epub ahead of print])
*** Outcome: Grade 3-4 mucositis honey 15% vs. no honey 65% (SS); candidiasis 15% vs. 60% (SS); aerobic pathogens 15% vs. 65% (SS)
*** Conclusion: Prophylaxis with pure natural honey effective in reducing mucositis

## NeutraSal

* NeutraSal, Invado Pharmaceuticals, LLC (http://www.neutrasal.com/)
* NeutraSal is a prescription supersaturated calcium phosphate rinse that is indicated to treat the painful symptoms associated with Oral Mucositis, Xerostomia, and Sjögren's Syndrome.
* NeutraSal is packaged in boxes of 30 or 120 single-use packets of dissolving powder.
* Dissolve one packet of NeutraSal in a clean glass of approximately 30 ml (1 ounce) of tap, distilled or bottled water. Use immediately after the solution appears clear or nearly clear. Stir if necessary. Swish half the solution in your mouth thoroughly for 1 minute then spit it out. Repeat swishing with the remaining half of the solution and spit out again.
* 4 doses per day from the onset of cancer treatment or as needed (PRN). Up to 10 doses per day may be used if severe pain from mucositis is experienced.
* The NeutraSal Direct Access Program provides product for patients who may require NeutraSal treatment regardless of their insurance or financial situation.

## GelClair

* GelClair, OSI Pharmaceuticals (Product information) - individual packets contain a powder that is mixed with water, and then the solution is rinsed in the mouth, then spit.
** Prescribing info: Each GelClair DosePak box contains 21 packets. Use 3 times a day or as needed. No eating or drinking for 1 hr following treatment.

## OraMagic

* OraMagic Oral Wound Rinse (swish 15 cc in mouth for 1 min or more qid and/or prn. Can swallow. Avoid food & drink for one hour following use. Supplied as 7.4g powder, makes 210 cc solution. One month supply = 9 bottles.) Supplier: MPM Medical
    Can also spray on involved skin such as perineum.
* OraMagic Patch (cut to correct size and apply to areas in the mouth, prn. Size: 4 inch diameter.)
    Can also use topically when covered with an outer bandage.
* RTOG 96-01
* RTOG 99-01 (2000-2) - Phase III, +/- GM-CSF for mucositis during RT.
** PMID 17293228 (2007) - negative trial. no difference in mucositis scores

## Palifermin

* Recombinant keratinocyte growth factor (KGF)
* Multi-national -- palifermin vs placebo.
** 188 pts. Randomized. 70 Gy RT with cisplatin (100 mg/m2 q3w x 3). Randomized to +/- palifermin (180 mcg/kg given before chemo/RT and once weekly)
** 2011 PMID 21670453 -- "Palifermin Reduces Severe Mucositis in Definitive Chemoradiotherapy of Locally Advanced Head and Neck Cancer: A Randomized, Placebo-Controlled Study." (Le QT, J Clin Oncol. 2011 Jul 10;29(20):2808-2814.)
*** Severe oral mucositis reduced 54% vs 69% (SS). Median time to severe OM 47 vs 35 days; median duration of OM 5 vs 26 days, gr 2 xerostomia 67% vs 80%; however, not SS. No significant difference in the use of opioid analgesics, mouth and throat soreness scores, and chemo/RT compliance. Adverse events: rash, flushing, dysgeusia. No difference in OS or PFS.
*** Conclusion: "Although palifermin reduced severe functional OM, its role in the management of locally advanced HNC during chemoradiotherapy remains to be elucidated."
* Europe; Post-op RT -- palifermin vs placebo.
** 186 pts. Multicenter. Randomized, double blind, placebo controlled. 60-66 Gy post-op RT. Cisplatin (100 mg/m2 q3w). Randomized to +/- palifermin (120 mcg/kg given 3 days before, and weekly during RT).
** 2011 PMID 21670447 -- "Palifermin Decreases Severe Oral Mucositis of Patients Undergoing Postoperative Radiochemotherapy for Head and Neck Cancer: A Randomized, Placebo-Controlled Trial." (Henke M, J Clin Oncol. 2011 Jul 10;29(20):2815-2820.)
*** Severe oral mucositis in 51% vs 67% (SS). Time to severe OM 45 vs 32 days; median duration 4.5 vs 22 days. No difference in mouth and throat soreness scores or treatment breaks.
*** Conclusion: "Palifermin reduced the occurrence of severe oral mucositis in patients with head and neck cancer undergoing postoperative radiochemotherapy. Additional clinical exploration of palifermin with postoperative radiochemotherapy would be useful."
* Multi-national -- palifermin vs. placebo
** Randomized, Phase II, 2:1. 99 patients with advanced H&N, undergoing RT (70/35 or split-course hyperfractionated 72/60) with concurrent chemotherapy (cisplatin 20 mg/m2 + 5-FU 1000 mg/m2). Arm 1) palifermin 60 μg/kg vs. Arm 2) placebo x 10 doses
** 2008 PMID 18487568 -- "Phase II study of palifermin and concurrent chemoradiation in head and neck squamous cell carcinoma." (Brizel DM, J Clin Oncol. 2008 May 20;26(15):2489-96.)
*** Outcome: median duration of G2+ mucositis palifermin 6.5 weeks vs. placebo 8.1 weeks (NS); palifermin more beneficial in hyperfractionated RT than standard RT
*** Toxicity: comparable
*** Conclusion: Well tolerated, but no impact on morbidity of concurrent chemo-RT
* 2006 PMID 16391299 — "Palifermin Reduces Patient-Reported Mouth and Throat Soreness and Improves Patient Functioning in the Hematopoietic Stem-Cell Transplantation Setting." Stiff PJ et al. J Clin Oncol. 2006 Nov 20;24(33):5186-93.
* 2006 PMID 17075109 — "Palifermin Reduces the Incidence of Oral Mucositis in Patients With Metastatic Colorectal Cancer Treated With Fluorouracil-Based Chemotherapy." Rosen LS et al. J Clin Oncol. 2006 Nov 20;24(33):5194-200

## Benzydamine

* A topical antiinflammatory with analgesic, anesthetic, and antimicrobial effects.
* Randomized trials support that benzydamine reduces the number and severity of oral ulcers and decreases pain in radiation-induced mucositis.

## Tetracaine (oral gel)

* Italy, PMID 16246498 (2006) — "Tetracaine oral gel in patients treated with radiotherapy for head-and-neck cancer: final results of a phase II study." Alterio D et al. Int J Radiat Oncol Biol Phys. 2006 Feb 1;64(2):392-5.
** 1.5% gel applied 30 min before and after meals (usually 6x/day).

## Caphosol (calcium phosphate mouth rinse)

* Tufts -- caphosol + fluoride vs. fluoride alone
** Randomized. 95 patients undergoing stem cell transplant. Arm 1) Caphosol + fluoride vs. Arm 2) fluoride alone
** 2003 PMID 12692611 -- "A prospective, randomized trial for the prevention of mucositis in patients undergoing hematopoietic stem cell transplantation." (Papas AS, Bone Marrow Transplant. 2003 Apr;31(8):705-12.)
*** Outcome: Mucositis days Caphosol 3.7 days vs. control 7.2 days (SS); duration of pain 2.9 vs. 7.7 (SS); morphine dose 34 mg vs. 123 mg, days of morphine 1.3 days vs. 4.0 days (SS); and days to onset of ANC 11.1 days vs. 12.6 days
*** Conclusion: Caphosol is superior to fluoride rinse alone for oral mucositis

## Iseganan

* Multi-National (2000-2001) -- iseganan vs. placebo vs supportive care
** Randomized, 3 arms. 545 patients with RT for H&N cancer. Arm 1) iseganan solution (microbicidal solution) vs. Arm 2) placebo vs. Arm 3) standard oral care
** 2004 PMID 14967419 -- "A multinational, randomized phase III trial of iseganan HCl oral solution for reducing the severity of oral mucositis in patients receiving radiotherapy for head-and-neck malignancy." (Trotti A, Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):674-81.)
*** Outcome: No ulcerative mucositis iseganan 9% vs. placebo 9% (NS) vs. supportive care 2% (SS). No difference in mouth pain or difficulty swallowing. Some benefit for nausea
*** Toxicity: No significant difference
*** Conclusion: Iseganan oral solution safe but didn't reduce risk of ulcerative mucositis

## Topical Morphine

* Lucerne, Switzerland -- topical morphine vs placebo
** Randomized, double-blind crossover. 18 patients with H&N cancer. Arm 1) Topical oral application of 2/1000 morphine solution x day 1-3 vs. Arm 2) placebo mouthwash. Crossover on days 4-6
** 2009 PMID 19827964 -- "Effect of Topical Morphine (Mouthwash) on Oral Pain Due to Chemotherapy- and/or Radiotherapy-Induced Mucositis: A Randomized Double-Blinded Study." (Vayne-Bossert P, J Palliat Med. 2009 Oct 14. [Epub ahead of print])
*** Outcome: Pain alleviation 1 hour after mouthwash improved with gesture of mouthwash (SS) and morphine (SS). Duration of relieve 124 minutes
*** Conclusion: Possible analgesic effect of topical morphine

## Doxepin

* NCCTG N09C6, Alliance for Clinical Trials in Oncology (NCCTG/CALGB/ACOSOG) (2010-2012) -- doxepin rinse vs placebo
** Protocol: PDF. Questionnaire: PDF
** Randomized, cross-over. 140 eligible pts undergoing definitive RT (>50 Gy, including > 1/3 of oral cavity) with oral mucositis pain rated >= 4/10. Randomized to doxepin oral rinse x 1 min and spit (25 mg in 5 mL water -- prepared as 10 mg/mL x 2.5 mL = 25 mg. Diluted with 2.5 mL water to make 5 mL.) Pain assessed at baseline
** 2012 Abstract - ASTRO 2012 LBA #1 PDF (Miller RC, Int J Radiat Oncol Biol Phys Vol. 85, Issue 1, Page 21)
*** Pain reduction AUC greater for doxepin (-9.1) vs placebo (-4.7), SS; similar crossover (-7.9 vs -5.6, SS). Doxepin well tolerated but caused stinging/burning, unpleasant taste, and drowsiness. 64% of pts continued on doxepin in the optional continuation phase.
*** Conclusion: "This study sets a new standard of care for the treatment of oral pain due to radiation-related oral mucositis."
** 2014 PMID 24733799 Abstract -- "Doxepin Rinse Versus Placebo in the Treatment of Acute Oral Mucositis Pain in Patients Receiving Head and Neck Radiotherapy With or Without Chemotherapy: A Phase III, Randomized, Double-Blind Trial (NCCTG-N09C6 [Alliance])" (Leenstra JL, J Clin Oncol -- online before print Apr 14, 2014.)
*** Conclusion: "A doxepin rinse diminishes OM pain. Further studies are warranted to determine its role in the management of OM."
* University of Illinois - Chicago, 2006 PMID 16861436 (full text) -- "Oral doxepin rinse: the analgesic effect and duration of pain reduction in patients with oral mucositis due to cancer therapy." (Epstein JB, Anesth Analg. 2006 Aug;103(2):465-70)
** 51 pts. 5 mg/ml oral rinse. overall 70% decrease in pain.

## Guidelines

* 2004 PMID 15108223 Full text — "Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis." Rubenstein EB et al. Cancer. 2004 May 1;100(9 Suppl):2026-46.