Abstract

Objective: Oral mucositis occurs in 75% to 100% of allogeneic HSCT recipients can cause pain, facilitate infections, delay discharge, and threaten life. The aim of the study was to evaluate prophylaxis with the remineralizing mouthwash solution of supersaturated calcium phosphate rinse (SCPR) with Fomukal on measures of severity of mucositis and consequent interventions and complications, in comparison to Caphosol, already evaluated post-transplant. Materials/Methods: In this prospective, randomized, non-inferiority trial, 46 patients undergoing allogeneic HSCT were equally randomized to Fomukal or Caphosol, each administered four times daily from initiation of conditioning until the granulocyte count ≥0.2 G/L. Hematologist measured the daily severity of mucositis according to a WHO scale and patients self-assessed its symptoms. Need for analgesics, anti-infectious drugs, total parenteral nutrition (TPN) and incidence of complications were also assessed. Results: Fomukal vs. Caphosol groups had the same all following indicators: median measures of WHO oral mucositis reduction (0 vs. 2; P = NS), length of disease course (0 vs. 6 days; P = NS), peak and mean mouth (1 vs. 2; P = NS and 0.06 vs. 1; P = NS) and throat pain (1 vs. 1; P = NS and 0.22 vs. 0.31; P = NS), and peak and mean swallowing problems (1 vs. 1; P = NS and 0.19 vs. 0.25; P = NS). Analgesics need (7 vs. 10 patients; 0 vs. 0 days; P = NS) and the need for antifungals (1 vs. 2 drugs; P = NS) were not different, while the need for antibiotics and antivirals (3.5 vs. 5 drugs; P = 0.011 and 1 vs. 2 drugs; P = 0.023) were lower in the Fomukal group. Measures of complications: infections (7 vs. 12 patients, P = NS) and a GVHD (13 vs. 14 patients, P = NS, grade 1 vs. 1, P = NS) did not differ. Discussion: Both SCPR mouth rinses, Fomukal and Caphosol, were associated with similar effectiveness in reducing severity of oral mucositis.

References

• 1. Bhatt N., Naithani R., Gupta S.K.: Supersaturated calcium phosphaterinse in prevention and treatment of mucositis in patientsundergoing hematopoietic stem cell transplant. Exp. Clin. Transplant.,2017; 15: 567–570
  Google Scholar
• 2. Chaudhry H.M., Bruce A.J., Wolf R.C., Litzow M.R., Hogan W.J.,Patnaik M.S., Kremers W.K., Philipps G.L., Hashmi S.K.: The incidenceand severity of oral mucositis among allogeneic hematopoieticstem cell transplantation patients: A systematic review. Biol.Blood Marrow. Transplant., 2016; 22: 605–616
  Google Scholar
• 3. Cinausero M., Aprile G., Ermacora P., Basile D., Vitale M.G.,Fanotto V., Parisi G., Sonis S.T.: New frontiers in the pathobiologyand treatment of cancer regimen-related mucosal injury. Front.Pharmacol., 2017; 8: 354
  Google Scholar
• 4. Cutler C., Li S., Kim H.T., Laglenne P., Szeto K.C., HoffmeisterL., Harrison M.J., Ho V., Aleya E., Lee S.J., Soiffer R., Sonis S., AntinJ.H.: Mucositis after allogeneic hematopoietic stem cell transplantation:A cohort study of methotrexate- and non-methotrexatecontaininggraft-versus-host disease prophylaxis regimens. Biol.Blood Marrow Transplant., 2005; 11: 383-388
  Google Scholar
• 5. Daugėlaitė G., Užkuraitytė K., Jagelavičienė E., Filipauskas A.:Prevention and treatment of chemotherapy and radiotherapy inducedoral mucositis. Medicina, 2019; 55: 25
  Google Scholar
• 6. Durrant S., Pico J.L., Schmitz N., Blaise D., Harousseau J.L., SzerJ., Boogaerts M., Finke J., Goldstone A.H., Borkett K., Heard R.G.:A phase 1 study of recombinant human keratinocyte growth factor(rHuKGF) in lymphoma patients receiving high-dose chemotherapy(HDC) with autologous peripheral blood progenitor celltransplantation (autoPBPCT). Blood, 1999; 94: 708a
  Google Scholar
• 7. Eilers J., Harris D., Henry K., Johnson L.A.: Evidence-based interventionsfor cancer treatment-related mucositis: Putting evidenceinto practice. Clin. J. Oncol. Nurs., 2014; 18: 80–96
  Google Scholar
• 8. Epstein J.B., Schubert M.M.: Oropharyngeal mucositis in cancertherapy. Review of pathogenesis, diagnosis, and management.Oncology, 2003; 17: 1767–1779
  Google Scholar
• 9. Gabrilove J.L., Jakubowski A., Scher H., Sternberg C., Wong G.,Grous J., Yagoda A., Fain K., Moore M.A., Clarkson B., Oettgen H.F.,Alton K., Welte K., Souza L.: Effect of granulocyte colony-stimulatingfactor on neutropenia and associated morbidity due tochemotherapy for transitional-cell carcinoma of the urothelium.N. Engl. J. Med., 1988; 318: 1414–1422
  Google Scholar
• 10. Haverman T.M., Raber-Durlacher J.E., Rademacher W.M.,Vokurka S., Epstein J.B., Huisman C., Hazenberg M.D., de Soet J.J.,de Lange J., Rozema F.R.: Oral complications in hematopoietic stemcell recipients: The role of inflammation. Mediators Inflamm.,2014; 2014: 378281
  Google Scholar
• 11. Kiprian D., Jarząbski A., Kawecki A.: Evaluation of efficacy ofCaphosol in prevention and alleviation of acute side effects in patientstreated with radiotherapy for head and neck cancers. Contemp.Oncol., 2016; 5: 389–393
  Google Scholar
• 12. Kiprian D., Rolski W., Michalski W.: Evaluation the efficacy ofFomukal for treatment of oral mucositis induced by radiation therapyin head and neck cancer patients. Abstracts of the MASCC/ISOOAnnual Meeting 2018. Support. Care Cancer, 2018; 26: S150–S151
  Google Scholar
• 13. Kröner A., Aerts E., Schanz U., Spirig R.: Caphosol ® versusstate-of-the-art mouth care in patients with allogeneic stem celltransplantation: A randomized controlled trial. J. Nurs. Care, 2016;5: 1–7|
  Google Scholar
• 14. Lalla R.V., Bowen J., Barasch A., Elting L., Epstein J., KeefeD.M., McGuire D.B., Migliorati C., Nicolatou‐Galitis G., PetersonD.E., Raber-Durlacher J.E., Sonis S.T., Elad S.: The Mucositis GuidelinesLeadership Group of the Multinational Association of SupportiveCare in Cancer and International Society of Oral Oncology(MASCC=ISOO). MASCC/ISOO clinical practice guidelines for themanagement of mucositis secondary to cancer therapy. Cancer,2014; 120: 1453–1461
  Google Scholar
• 15. Lambrecht M., Mercier C., Geussens Y., Nuyts S.: The effect ofa supersaturated calcium phosphate mouth rinse on the developmentof oral mucositis in head and neck cancer patients treatedwith (chemo)radiation: A single-center, randomized, prospectivestudy of a calcium phosphate mouth rinse + standard of care versusstandard of care. Support. Care Cancer, 2013; 21: 2663–2670
  Google Scholar
• 16. Lee S.: Mineral derivatives in alleviating oral mucositis duringcancer therapy: A systematic review. Peer J., 2015; 3: e765
  Google Scholar
• 17. Markiewicz M., Dzierzak-Mietla M., Frankiewicz A., Zielinska P.,Koclega A., Kruszelnicka M., Kyrcz-Krzemien S.: Treating oral mucositiswith a supersaturated calcium phosphate rinse: Comparisonwith control in patients undergoing allogeneic hematopoietic stemcell transplantation. Support. Care Cancer, 2012; 20: 2223–2229
  Google Scholar
• 18. Miyamoto C.T., Wobb J., Micaily B., Li S., Achary M.P.: A retrospectivematch controlled study of supersaturated calcium phosphateoral rinse vs. supportive care for radiation induced oralmucositis. J. Cancer Ther., 2012; 3: 630–636
  Google Scholar
• 19. Nasilowska-Adamska B., Rzepecki P., Manko J., Czyz A., MarkiewiczM., Federowicz I., Tomaszewska A., Piatkowska-Jakubas B.,Wrzesien-Kus A., Bieniaszewska M., Duda D., Szydlo R., HalaburdaK., Szczepinski A., Lange A., et al.: The influence of palifermin(Kepivance) on oral mucositis and acute graft versus host diseasein patients with hematological diseases undergoing hematopoieticstem cell transplant. Bone Marrow Transplant., 2007; 40: 983–988
  Google Scholar
• 20. Nemunaitis J., Rosenfeld C.S., Ash R., Freedman M.H., Deeg H.J.,Appelbaum F., Singer J.W., Flomenberg N., Dalton W., Elfenbein G.J.,Rifkin R., Rubin A., Agosti J., Hayes F.A., Holcenberg J., ShadduckR.K.: Phase III randomized, double-blind placebo-controlled trialof rhGM-CSF following allogeneic bone marrow transplantation.Bone Marrow Transplant., 1995; 15: 949–954
  Google Scholar
• 21. Papas A.S., Clark R.E., Martuscelli G., O’Loughlin K.T., JohansenE., Miller K.B.: A prospective, randomized trial for the preventionof mucositis in patients undergoing hematopoietic stem cell transplantation.Bone Marrow Transplant., 2003; 31: 705–712
  Google Scholar
• 22. Price D.D., McGrath P.A., Rafii A., Buckingham B.: The validationof visual analogue scales as ratio scale measures for chronicand experimental pain. Pain, 1983; 17: 45–56
  Google Scholar
• 23. Quinn B.: Efficacy of a supersaturated calcium phosphate oralrinse for the prevention and treatment of oral mucositis in patientsreceiving high-dose cancer therapy: A review of current data. Eur.J. Cancer Care, 2013; 22: 564–579
  Google Scholar
• 24. Rao N.G., Trotti A., Kim J., Schell M.J., Zhao X., Amdur R.J., BrizelD.M., Chambers M.S., Caudell J.J., Miyamoto C., Rosenthal D.I.: Phase II multicenter trial of Caphosol for the reduction of mucositisin patients receiving radiation therapy for head and neck cancer.Oral. Oncol., 2014; 50: 765–769
  Google Scholar
• 25. Raphael M.F., den Boer A.M., Kollen W.J., Mekelenkamp H.,Abbink F.C., Kaspers G.J., Zomer-Kooijker K., Molmans B.H., TissingW.J.: Caphosol, a therapeutic option in case of cancer therapyinducedoral mucositis in children? Results from a prospectivemulticenter double blind randomized controlled trial. Support.Care Cancer, 2014; 22: 3–6
  Google Scholar
• 26. Schwerkoske J., Schwartzberg L., Weaver C., SchwertschlagU.S., Goodfellow J., Bedrosian C.L.: A phase I double-masked, placebo-controlled study to evaluate tolerability of neumega (rh IL-11;opreleukin) to reduce mucositis in patients with solid tumorsor lymphoma receiving high dose chemotherapy with autologousperipheral blood stem cell reinfusion. Proc. Am. Soc. Clin. Oncol.,1999; 18: 2256
  Google Scholar
• 27. Sonis S.T.: The pathobiology of mucositis. Nat. Rev. Cancer,2004; 4: 277–284
  Google Scholar
• 28. Sonis S.T, Elting L.S., Keefe D., Peterson D.E., Schubert M.,Hauer-Jensen M., Bekele B.N., Raber-Durlacher J., Donnelly J.P.,Rubenstein E.B., Mucositis Study Section of the Multinational Associationfor Supportive Care in Cancer, International Society for OralOncology: Perspectives on cancer therapy-induced mucosal injury:Pathogenesis, measurement, epidemiology, and consequences forpatients. Cancer, 2004; 100: 1995–2025
  Google Scholar
• 29. Stiff P.: Mucositis associated with stem cell transplantation:Current status and innovative approaches to management. BoneMarrow Transplant., 2001; 27: S3–S11
  Google Scholar
• 30. Svanberg A., Öhrn K., Birgegård G.: Caphosol® mouthwashgives no additional protection against oral mucositis compared to cryotherapy alone in stem cell transplantation. A pilot study.Eur. J. Oncol. Nurs., 2015; 19: 50–53
  Google Scholar
• 31. Thomsen M., Vitetta L.: Adjunctive treatments for the preventionof chemotherapy- and radiotherapy-induced mucositis.Integr. Cancer Ther., 2018; 17: 1027–1047
  Google Scholar
• 32. Treister N., Nieder M., Baggott C., Olson E., Chen L., Dang H.,Krailo M., August A., Sung L.: Caphosol for prevention of oral mucositisin pediatric myeloablative haematopoietic cell transplantation.Br. J. Cancer, 2017; 116: 21–27
  Google Scholar
• 33. Vokurka S., Steinerova K., Karas M., Koza V.: Characteristicsand risk factors of oral mucositis after allogeneic stem cell transplantationwith FLU/MEL conditioning regimen in context withBU/CY2.Bone Marrow Transplant., 2009; 44: 601–605
  Google Scholar
• 34. Waśko-Grabowska A., Rzepecki P., Oborska S., Barzał J.,Gawroński K., Młot B., Szczylik C.: Efficiency of supersaturatedcalcium phosphate mouth rinse treatment in patients receivinghigh-dose melphalan or BEAM prior to autologous blood stem celltransplantation: A single-center experience. Transplant. Proc.,2011; 43: 3111–3113
  Google Scholar
• 35. Wong K.H., Kuciejewska A., Sharabiani M.T., Ng-Cheng-Hin B.,Hoy S., Hurley T., Rydon J., Grove L., Santos A., Ryugenji M., BhideS.A., Nutting C.M., Harrington K.J., Newbold K.L.: A randomisedcontrolled trial of Caphosol mouthwash in management of radiation-induced mucositis in head and neck cancer. Radiother. Oncol.,2017; 122: 207–211
  Google Scholar
• 36. Younus J., Kligman L., Jawaid M.A., Dhalla A.: Treatmentof active mucositis with Caphosol (calcium phosphate):A retrospective case-series. World J. Oncol., 2013; 4: 147–150
  Google Scholar

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