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01-10-2007 | Original Article

A phase III randomized double-blind placebo-controlled clinical trial to determine the efficacy of low level laser therapy for the prevention of oral mucositis in patients undergoing hematopoietic cell transplantation

Authors: Mark M. Schubert, Fernanda P. Eduardo, Katherine A. Guthrie, Jean-Claude Franquin, Rene-Jean J. Bensadoun, Cesar A. Migliorati, C. Michele E. Lloid, Carlos P. Eduardo, Niccoli-Filho Walter, Marcia M. Marques, Mohd Hamdi

Published in: Supportive Care in Cancer | Issue 10/2007

Abstract

Introduction

Oral mucositis (OM) is a significant early complication of hematopoietic cell transplantation (HCT). This phase III randomized double-blind placebo-controlled study was designed to compare the ability of 2 different low level GaAlAs diode lasers (650 nm and 780 nm) to prevent oral mucositis in HCT patients conditioned with chemotherapy or chemoradiotherapy.

Materials and methods

Seventy patients were enrolled and randomized into 1 of 3 treatment groups: 650 nm laser, 780 nm laser or placebo. All active laser treatment patients received daily direct laser treatment to the lower labial mucosa, right and left buccal mucosa, lateral and ventral surfaces of the tongue, and floor of mouth with energy densities of 2 J/cm². Study treatment began on the first day of conditioning and continued through day +2 post HCT. Mucositis and oral pain was measured on days 0, 4, 7, 11, 14, 18, and 21 post HCT.

Results

The 650 nm wavelength reduced the severity of oral mucositis and pain scores. Low level laser therapy was well-tolerated and no adverse events were noted.

Discussion

While these results are encouraging, further study is needed to truly establish the efficacy of this mucositis prevention strategy. Future research needs to determine the effects of modification of laser parameters (e.g., wavelength, fluence, repetition rate of energy delivery, etc.) on the effectiveness of LLE laser to prevent OM.

Bellm LA, Epstein JB, Rose-Ped A et al (2000) Patient reports of complications of bone marrow transplantation. Support Care Cancer 8:33–39PubMed

Stiff P (2001) Mucositis associated with stem cell transplantation: current status and innovative approaches to management. Bone Marrow Transplant 27(Suppl 2):S3–S11PubMedCrossRef

Sonis ST, Oster G, Fuchs H, Bellm L, Bradford WZ, Edelsberg J et al (2001) Oral mucositis and the clinical and economic outcomes of hematopoietic stem cell transplantation. J Clin Oncol 19:2201–2205PubMed

Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M et al (2004) Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer 100(Supp 9):1995–2025PubMedCrossRef

Rubenstein EB, Peterson DE, Schubert M, Keefe D, McGuire D, Epstein J et al (2004) Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer 100(Supp 9):2026–2046PubMedCrossRef

Schubert, MM, Williams B, Lloid ME, Donaldson G, Chapko MK (1992) Clinical assessment for the rating of oral mucosal changes associated with bone marrow transplantation: development of an oral mucositis index. Cancer 69:2469–2477PubMedCrossRef

Kolbinson DA, Schubert MM, Flournoy N, Truelove EL (1988) Early oral changes following bone marrow transplantation. Oral Surg Oral Med Oral Pathol 66:130–138PubMedCrossRef

Chapko MK, Syrjala KL, Schilter L, Cummings C, Sullivan KM (1989) Chemotherapy toxicity during bone marrow transplantation: time course and variation in pain and nausea. Bone Marrow Transplant 4:181–186PubMed

Chapko MK, Syrjala KL, Bush N, Jedlow C, Yanke MR (1991) Development of a behavioral measure of mouth pain, nausea, and wellness for patients receiving radiation and chemotherapy. J Pain Symptom Manage 6:15–23PubMedCrossRef

10.

Bearman SI, Applebaum FR, Buckner CD et al (1988) Regimen-related toxicity in patients undergoing bone marrow transplantation. J Clin Oncol 6:1562–1568PubMed

11.

Chapko NK, Syrjala KL, Schilter L et al (1989) Chemoradiotherapy toxicity during bone marrow transplantation: time course and variation in pain and nausea. Bone Marrow Transplant 4:181–186PubMed

12.

Wardley AM, Jayson GC, Swindell R, Morgenstern GR, Chang J, Bloor R et al (2000) Prospective evaluation of oral mucositis in patients receiving myeloablative conditioning regimens and haemopoietic progenitor rescue. Br J Haematol 110:292–299PubMedCrossRef

13.

Sonis ST (2004) The pathobiology of mucositis. Nat Rev Cancer 4:227–284CrossRef

14.

Blijlevens NMA, Donnelly JP, De Pauw BE (2000) Mucosal barrier injury: biology, pathology, clinical counterparts and consequences of intensive treatment for haematological malignancy: an overview. Bone Marrow Transplant 25:1269–1278PubMedCrossRef

15.

Tardieu C, Cowen D, Thirion, X, Franquin JC (1996) Quantitative scale of oral mucositis associated with autologous bone marrow transplantation. Eur J Cancer 32:381–387

16.

Epstein JB, Schubert MM (2003) Oropharyngeal mucositis in cancer therapy. Review of pathogenesis, diagnosis, and management. Oncology (Williston Park) 17:1767–1779 (discussion 1779–1782, 1791–1792)

17.

Spielberger R, Stiff P, Bensinger W, Gentile T, Weisdorf D, Kewalramani T et al (2004) Palifermin for oral mucositis after intensive therapy for hematologic cancers. N Engl J Med 351:2590–2598PubMedCrossRef

18.

Schubert MM, Franquin JC, Niccoli-Filho, Marical F, Lloid M, Kelly J (1997) Effects of low-energy laser on oral mucositis: a phase I/II pilot study. Cancer Res Wkly 7:14

19.

Barasch A, Peterson DE, Tanzer JM, D’Ambrosio JA, Nuki K, Schubert MM et al (1995) Helium–neon laser effects on conditioning-induced oral mucositis in bone marrow transplantation patients. Cancer 76:2550–2556PubMedCrossRef

20.

Cowen D, Tardieu C, Schubert MM, Peterson D, Resbeut M, Faucher C et al (1997) Low energy HeNe laser in the prevention of oral mucositis in patients undergoing bone marrow transplant: results of a double blind randomized trial. Int J Radiat Oncol Biol Phys 38:697–703PubMedCrossRef

21.

Bensadoun RJ, Franquin JC, Ciais G, Carcout V, Schubert MM, Viot M et al (1999) Low-energy He/Ne laser in the prevention of radiation-induced mucositis. A multicenter phase III randomized study in patients with head and neck cancer. Support Care Cancer 7:244–252PubMedCrossRef

22.

Migliorati C, Massumoto C, Eduardo FP, Muller KP, Carrieri T, Haypek P et al (2001) Low-energy laser therapy in oral mucositis. Science 1:97–100

23.

Bensadoun RJ, Ciais G (2002) Radiation and chemotherapy-induced mucositis in oncology: results of multicenter phase III studies. The Journal of Oral Laser Applications 2:115–120

24.

Wong SF, Wilder-Smith P (2002) Pilot study of laser effects on oral mucositis in patients receiving chemotherapy. Cancer J 8:247–254PubMedCrossRef

25.

Nes AG, Posso MB (2005) Patients with moderate chemotherapy-induced mucositis: pain therapy using low intensity lasers. Int Nurs Rev 52:68–72PubMedCrossRef

26.

Arun Maiya G, Sagar MS, Fernandes D (2006) Effect of low level helium–neon (He–Ne) laser therapy in the prevention & treatment of radiation induced mucositis in head & neck cancer patients. Indian J Med Res 124(4):399–402PubMed

27.

Antunes HS, de Azevedo AM, da Silva Bouzas LF et al (2006) Low power laser in the prevention of induced oral mucositis in bone marrow transplantation patients: a randomized trial. Blood 109:2250–2255PubMedCrossRef

28.

Genot MT, Klastersky J (2005) Low-level laser for prevention and therapy of oral mucositis induced by chemotherapy or radiotherapy. Curr Opin Oncol 17:236–240PubMedCrossRef

29.

Braverman B, McCarthy R, Ivankovich AD, Forde DE, Overfield M, Bapna MS (1989) Effect of HeNe and infrared laser irradiation on wound healing in rabbits. Lasers Surg Med 9:50–58PubMedCrossRef

30.

Boratoletto R, Silva NS, Zangaro RA et al (2004) Mitochondrial membrane potential after low-power laser irradiation. Lasers Med Sci 18:204–206CrossRef

31.

Loevshall H, Arenholt-Bindslev D (1994) Effect of low level diode irradiation of human oral mucous fibroblasts in vitro. Lasers Surg Med 59:167–170

32.

Almeida-Lopes L, Rigau J, Zangaro RA, Guidugli-Neto J, Jaeger MM (2001) Comparison of the low level laser therapy effects on cultured human gingival fibroblasts proliferation using different irradiance and same fluence. Lasers Surg Med 29:179–184PubMedCrossRef

33.

Pereira AN, Eduardo CP, Matson E, Marques MM (2002) Effect of low-power laser irradiation on cell growth and procollagen synthesis of cultured fibroblasts. Lasers Surg Med 31:263–267PubMedCrossRef

34.

Marques MM, Pereira NA, Fujihara NA, Nogueira FN, Eduardo CP (2004) Effect of low-power laser irradiation on protein synthesis and ultrastructure of human gingival fibroblasts. Lasers Surg Med 34:260–265PubMedCrossRef

35.

Sonis ST (2002) The biologic role for nuclear factor-kappaB in disease and its potential involvement in mucosal injury associated with anti-neoplastic therapy. Crit Rev Oral Biol Med 13:380–389PubMedCrossRef

36.

Sonis ST, Scherer J, Phelan S, Lucey CA, Barron JE, O’Donnell KE et al (2002) The gene expression sequence of radiated mucosa in an animal mucositis model. Cell Prolif 35(Suppl 1):93–102PubMedCrossRef

37.

Pereira AN, Eduardo CP, Matson E, Marques MM (2002) Effect of low-power laser irradiation on cell growth and procollagen synthesis of cultured fibroblasts. Lasers Surg Med 31:263–267PubMedCrossRef

Title: A phase III randomized double-blind placebo-controlled clinical trial to determine the efficacy of low level laser therapy for the prevention of oral mucositis in patients undergoing hematopoietic cell transplantation
Authors: Mark M. Schubert
Fernanda P. Eduardo
Katherine A. Guthrie
Jean-Claude Franquin
Rene-Jean J. Bensadoun
Cesar A. Migliorati
C. Michele E. Lloid
Carlos P. Eduardo
Niccoli-Filho Walter
Marcia M. Marques
Mohd Hamdi
Publication date: 01-10-2007
Publisher: Springer-Verlag
Published in: Supportive Care in Cancer / Issue 10/2007
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI: https://doi.org/10.1007/s00520-007-0238-7

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Abstract

Introduction

Materials and methods

Results

Discussion

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