Double-blind, randomized pilot study of bioadhesive chlorhexidine gel in the prevention and treatment of mucositis induced by chemoradiotherapy of head and neck cancer

Med O al Pa ol O al Ci Bucal. 2015 May 1;20 (3):e378-85. Bioadhesi e chlo hexidine gel and mucosi is e378 Jou nal sec ion: O al Su ge y Publica ion Types: Resea ch Double-blind, andomized pilo s udy o bioadhesi e chlo hexidine gel in he p e en ion and ea men o mucosi is induced by chemo adio he apy o head and neck cance Rosa-Ma ia Diaz-Sanchez 1, Je ónimo Pachón-Ibáñez 2, Fá ima Ma ín-Conde 1, Ángela Rod íguez-Caballe o 1, Jose-Luis Gu ie ez-Pe ez 1,2, Daniel To es-Laga es 1 1 Den al School. Uni e si y o Se ille 2 “Vi gen del Rocío” Uni e si y Hospi al Co espondence: Depa amen o S oma ology School o Den is y - Uni e si y o Se ille “Vi gen del Rocío” Uni e si y Hospi al C/ A icena s/n 41009. Se ille. Spain daniel [email protected] Recei ed: 26/08/2014 Accep ed: 23/10/2014 Abs ac Backg ound: To e alua e, in an ini ial way, he e ec i eness o bioadhesi e chlo hexidine gel 0.2% e sus placebo as a p e en i e and he apeu ic in e en ion o o al mucosi is induced by adia ion he apy and chemo he apy in pa ien s diagnosed wi h head and neck cance ea ed wi h chemo adio he apy. Ma e ial and Me hods: �n his pilo s udy, 7 pa ien s ( ange o age: 18- 65), ha ing his ological documen ed diag-Me hods: �n his pilo s udy, 7 pa ien s ( ange o age: 18- 65), ha ing his ological documen ed diag-e hods: �n his pilo s udy, 7 pa ien s ( ange o age: 18- 65), ha ing his ological documen ed diag-- 65), ha ing his ological documen ed diag- 65), ha ing his ological documen ed diag- nosis o squamous ca cinoma on he head and neck egion in s age ��� and �V, and ecei ing combined adia ion ea men and chemo he apy (cispla in 100 mg/m2 �V on days 1, 22, and 43 o i adia ion) we e s udied. Simul- aneously, a opical applica ion was pe o med wi h bioadhesi e chlo hexidine gel 0.2% in he s udy g oup, and he placebo gel o he con ol g oup in 5 applica ions pe day, om he ime o ini ia ion o cance ea men o 2 weeks a e comple ion o chemo- adio he apy ea men (11 weeks o ollow-up). The g ada ion o mucosi is, pain, analgesic consump ion, in ec ious complica ions, and ea men ole ance was measu ed. Resul s: A e 7 pa ien s comple ed he p o ocol, any di e ences we e obse ed be ween g oups in an in e al analysis. Mucosi is, pain, and ole ance was simila in bo h g oups. Conclusions: Ou esul s mus be in e p e ed wi h cau ion due o he educed sample size, bu he use o bioad- hesi e chlo hexidine gel 0.2% didn’ con ibu e clinical imp o emen o he o al mucosi is induced by adia ion he apy and chemo he apy. Key wo ds: Chlo hexidine, mucosi is, head and neck cance . Diaz-Sanchez RM, Pachón-�báñez J, Ma ín-Conde F, Rod íguez-Caba- lle o Á, Gu ie ez-Pe ez JL, To es-Laga es D. Double-blind, andomi-. Double-blind, andomi-Double-blind, andomi- zed pilo s udy o bioadhesi e chlo hexidine gel in he p e en ion and ea men o mucosi is induced by chemo adio he apy o head and neck cance . Med O al Pa ol O al Ci Bucal. 2015 May 1;20 (3):e378-85. h p://www.medicinao al.com/medo al ee01/ 20i3/medo al 20i3p378.pd A icle Numbe : 20338 h p://www.medicinao al.com/ © Medicina O al S. L. C.I.F. B 96689336 - pISSN 1698-4447 - eISSN: 1698-6946 eMail: [email p o ec ed] Indexed in: Science Ci a ion �ndex Expanded Jou nal Ci a ion Repo s �ndex Medicus, MEDL�NE, PubMed Scopus, Embase and Emca e �ndice Médico Español doi:10.4317/medo al.20338 h p://dx.doi.o g/doi:10.4317/medo al.20338 Med O al Pa ol O al Ci Bucal. 2015 May 1;20 (3):e378-85. Bioadhesi e chlo hexidine gel and mucosi is e379 In odu ion O al mucosi is (OM) is conside ed one o he majo de- bili a ing side e ec s o cance he apy due o he di- ec adia ion o he mucosa wi h adio he apy o by he e ec o chemo he apy (1,2). This illness is desc ibed as he esul o in lamma ion changes in he epi helial and sub-epi helial cells i adia ed o a ec ed by he ea men , causing discom o in he pa ien s because o he gene alized e y hema, ank ulce a ion, and denu- da ion, associa ed wi h local pain as well, which cons- i u es he mos impo an clinical mani es a ions o o opha yngeal mucosi is (1,3). The induced pain makes i di icul o pa ien s o ea , swallow, speak, o pe o m o al hygiene measu es. These e ec s esul in weigh loss, dehyd a ion, and a isk o o al in ec ions (1). Today, adio he apy (RT) and chemo he apy (QT) cons- i u e as one o he mos commonly used combina ions o he apies o head and neck cance (H&NC). � has been demons a ed in p e ious s udies ha he associa- ion o hese ypes o ea men s esul mo e e ec i ely han using adio he apy alone. Ac ually, he mos e- quen ea men is he p og ammed sessions o QRT, being necessa y in mos cases o su gical in e en ion oo. The ea men mus be unin e up ed; i has been demons a ed ha he p oli e a ion isk o esidual u- mo cells is inc emen ed when he adio he apy o he p og ammed chemo he apy is abandoned o in e up- ed, causing ecu ences o he umo and a ec ing he li e quali y o he pa ien (4). Nine y pe cen o pa ien s wi h head and neck cance e- cei ing s anda d adio he apy and chemo adio he apy will de elop o opha yngeal mucosi is (3), a ying he incidence acco ding o he oncology ea men schedule (5). �n ao al lesions a e commonly localized in non-que- a inized o al mucosa, such as lip and buccal mucosa, la e al and an e io mucosa o he ongue, loo o he mou h, and so pala e. The ha d pala e and gums seem o be less suscep ible o he e ec s o chemo he apy and adio he apy (6). In a con en ional adio he apy, he i s adia ion dose (10 Gy) causes a hipe que a inized lesion, whe e a whi- ish appea ance can go unno iced. An ea ly sign o OM includes e y hema, which appea s a e app oxima ely 20 Gy o cumula i e adia ion dosage o head and neck umo s. A e 7–10 days, o a cumula i e dosage o 30 Gy, ulce s co e ed by a pseudomemb ane a e de ec ed; hese pseudomemb anes b ing on he bac e ial coloni- za ion wi h a high isk o sob ein ec ion, which a e as- socia ed wi h discom o and changes in pa ien die a y habi s. Radio-induced OM las s o a leas 2 o 6 weeks a e adia ion he apy has inished (7,8). OM induced by chemo he apy is usually mo e agg es- si e han ha caused by adio he apy. A e 5-8 days o ea men , e y hema appea s, and 2 days a e , edema and ulce a ion can be obse ed (7). E y hema is obse - ed a ound he i h–eigh h day o ea men , and in he ollowing days, edema and ulce a ion can be obse ed. A e he end o he chemo he apy ea men , he mucosa will need abou 7-10 days o eco e comple ely (7). Nowadays, he e a e a la ge numbe o ea men s ha we can choose om, bu he s a egies o educe o al muco- si is a e s ill unclea . Due o he impo ance o he OM, many s udies ha e been ca ied ou . Di e en echniques ha e been desc ibed like in ensi e o al ca e p o ocol, an imic obial agen s, an iin lamma o y agen s, ci op o- ec o s agen s, nu i ional supplemen s, bioes imulan s agen s, o na u al and homeopa hic agen s. Al hough all o hese ea men op ions exis (6,9-11) o p e en and ea mucosi is, he e is no gold-s anda d p o ocol ha is p ominen ly be e han he es because he e is no enough e idence desc ibing a ea men wi h p o en e i- ciency o su pass he o he ea men s o his condi ion (6,9,12-14). Chlo hexidine is app o ed o use as an an ibac e ial mou hwash a a concen a ion o 0.12% and 0.2% o p e- en he build-up o den al plaque and o p e en gingi- i is (9,15). � s b oad spec um o an ibac e ial ac i i y, minimal sys emic abso p ion, and abili y o bind o o al su aces led o he use o p ophylaxis in an a emp o p e- en he de elopmen o o al mucosi is (16). Howe e , i has some disad an ages such as he discolo a ion o ee- h, he bi e as e, and he unpleasan sensa ion (17,18). The aim o his pilo s udy was o e alua e, in an ini- ial way, he e ec i eness o bioadhesi e chlo hexidine gel 0.2% e sus placebo as a p e en i e and he apeu ic in e en ion o o al mucosi is induced by adia ion he- apy and chemo he apy in pa ien s diagnosed wi h head and neck cance ea ed wi h chemo adio he apy. Ma e ial and Me hods - Pa ien Cha ac e is ics and place o s udy The pilo s udy was conduc ed in he oncology de- pa men o he Uni e si y Hospi al “Vi gen del Rocío” in Se ille a e app o al om he local �n e nal Re iew Boa d. This was a p ospec i e, placebo-con olled, an- domized, and double-blind pilo s udy. The inclusion c i e ia was he ollowing: pa ien s aged 18-65, who had his ological documen ed diagnosis o squamous ca cinoma on he head and neck egion in s age III and IV acco ding o he TNM classi ica ion and who ecei ed combined adia ion ea men (con- en ional ac iona ion 70 Gy eaching he umo and a ec ed lymph nodes, and 50 Gy a he nodal a eas d a- inage in 9 weeks) and chemo he apy (cispla in 100 mg/ m2 �V on days 1, 22, and 43 o i adia ion). The pa ien s olun a ily exp essed hei in en ion o pa icipa e in he clinical ial wi h in o med consen be o e en olling in he s udy. The exclusion c i e ia was he ollowing: pa ien s who Med O al Pa ol O al Ci Bucal. 2015 May 1;20 (3):e378-85. Bioadhesi e chlo hexidine gel and mucosi is e380 ha e hype sensi i i y o an alle gy o any o he compo- nen s included in he s udy, pa ien s wi h H�V, diabe es and au oimmune diseases, and hose who do no ul ill all o he inclusion c i e ia men ioned abo e. A e ca ying ou his pilo s udy, 7 egis e ed pa ien s, 4 in he s udy g oup, and 3 in he con ol g oup, he s udy was s opped. All he pa ien s ul illed he pilo s udy. - S udy g oups Expe imen al/s udy g oup: �n he p o ocol o ea men , hese pa ien s pe o med opical applica ion wi h bio- adhesi e chlo hexidine gel 0.2%. �n he con ol g oup, hese pa ien s used a placebo gel in he way ha we spe- ci y below. - S udy design The s udy p o ocol consis ed o he adminis a ion o a mul i i amin ha con ained i amin E and Zinc Sul a e, he pe o mance o inses wi h 15 ml o Benzydamine o 2 minu es, 5 imes a day, and he local applica ion o ice on he o al mucosa a leas o 20 minu es on days 1, 22, and 43 o cance ea men (a e chemo he apy wi h cispla in), besides he applica ion o adio he apy o 9 weeks (exposed p e iously). Simul aneously, opical applica ion was pe o med wi h bioadhesi e chlo hexidine gel 0.2% in he s udy g oup and placebo gel o he con ol g oup in 5 applica ions pe day om he ime o ini ia ion o cance ea men o 2 weeks a e comple ion o chemo- adio he apy ea men ( o al ime o s udy was 77 days, 11 weeks). The pa ien was ins uc ed in he placemen o he gel (placebo o chlo hexidine) wi h a sy inge by ex ac ing a dose o 10 ml o each applica ion, 5 imes pe day, a e insing wi h benzydamine. The andomiza ion and double-blind ial was ca ied ou as ollows. Bo h gels we e p epa ed by LACER la- bo a o ies in Ba celona (Spain). The needed ha dwa e was added o all samples o ha e iden ical colo , la o , and ex u e, which in u n would be com o able o he pa ien . Pa ien s we e andomly assigned o ecei e ei- he p o ocol o o al ca e wi h chlo hexidine o placebo by selec ion o a sealed en elope ( andomized lis gene- a ed by compu e ). The pa ien sco ed daily in a bookle p o ided below o he onse o pain and i s in ensi y be o e applying he gel, immedia ely a e , and 3 hou s la e (using a isual analog scale numbe ed om 0 o 100) in he i s appli- ca ion o he gel du ing he day. � was also no ed in his bookle i he use o analgesics and/o an i-in lamma- o y o al mucosi is was equi ed, and in wha quan i y (numbe o pills and doses). The s udy was planned and ca ied ou in compliance wi h he Decla a ion o Helsinki and Good Clinical P ac ice. The pilo s udy p o ocol was app o ed by he Expe imen a ion E hics Commi ee (EC) o he Uni e - si y o Se ille and inanced by he Andalusian Heal h Se ice (Code S�G�- S0095). - Clinical assessmen p o ocol G ada ion, occu ence, and emission o mucosi is The in eg i y o he mucosa was assessed using he WHO c i e ia o he g ading o o al mucosi is on a scale o 0–4, whe e 0 is “no change,” 1 co esponds o “e y hema and/o pain,” 2 “ulce a ion and abili y o ea ,” 3 “ulce a ion and limi ed abili y o ea ,” and 4 “ul- ce a ion wi h hemo hage and nec osis.” The examine is always he same o a oid he a iabili y be ween di- e en examine s’ c i e ia. �ni ial explo a ion o he o al mucosa is eco ded be o e he beginning o chemo- adio he apy, and subsequen e iews we e ca ied ou weekly un il 2 weeks a e he ull cance ea men o he pa ien s. - Pain Pa ien s a ed pain sensa ion ollowing a isual analo- gue scale (VAS) la wi h alues anging om 0 (“no pain”) and he alue 100 (“unbea able pain”). This an- no a ion was made a home once a day h oughou he s udy, be o e applying he gel, immedia ely a e , and 3 hou s a e ( i s daily gel applica ion). - Adju an analgesics Pa ien s eco ded in he same bookle i hey ook anal- gesics o an i-in lamma o ies due o mucosi is, and hey speci ied he amoun o d ugs equi ed on a daily basis. - T ea men ole ance The e alua ion o ole ance was based on he equency wi h which pa ien s ha e had a leas one ad e se e en du ing he ial. The pa ien and in es iga o will sco e he global ole ance a he end o ea men by an o al 5-poin scale: 5 = e y good, 4 = good, 3 = mode a e, 2 = poo , and 1 = e y poo . - �n ec ious complica ions The in es iga o assessed he occu ence o complica- ions due o in ec ion o he lesions o mucosi is in wee- kly e iews du ing ea men . - Da a analysis Da a we e analyzed using SPSS 9 o Windows Suppo Uni Resea ch Hospi al Uni e si a io “Vi gen del Ro- cio.” We used he chi-squa e es o he analysis o he da a ob ained in he compa ison o quali a i e a iables and Mann–Whi ney U es o compa ison o means. Resul s �n his pilo s udy, 7 pa ien s wi h head and neck ca ci- noma ea ed wi h chemo- adio he apy we e andomi- zed and included in he in en ion- o- ea popula ion o e icacy analyses. The pa ien s consis ed o 5 men and 2 women wi h mean age o 59.57 ± 10.97 yea s. �n he con ol g oup, 3 pa ien s we e ea ed wi h a mean age o 63.3 ± 15.89 yea s. �n he expe imen al g oup, 4 pa- ien s we e ea ed wi h an a e age age o 56.75 ± 6.90 yea s (Table 1). All pa ien s we e unde going ea men chemo- adio he apy. Rega ding he equency o he hygienic habi s, 4 pa- Med O al Pa ol O al Ci Bucal. 2015 May 1;20 (3):e378-85. Bioadhesi e chlo hexidine gel and mucosi is e381 ien s had a equency o 3 imes pe day, 2 pa ien s 2 imes pe day, and 1 o hem 1 ime pe day. Howe e , in e ms o ha m ul habi s, only 2 pa ien s had no such habi , 2 o hem we e ex-smoke s, 2 we e smoke s and d inke s, and one o hem was a d inke (Table 2). The in eg i y o he mucosa o he WHO scale o mu- cosi is was sligh ly highe in he s udy g oup han in he con ol g oup, bu wi hou ob aining s a is ically signi- ican di e ences (p>0.05) (Table 3). �n ela ion o he pain associa ed wi h he applica ion o gel, a g ea e deg ee o pain p io o placemen in he s udy g oup han in he con ol g oup was obse ed (Fig. 1), al hough he pain a he ime o gel applica- ion and 1 hou la e o placemen was less in he s udy g oup e sus he con ol g oup (Figs. 2,3). Howe e , no di e ences in ends we e ound be ween he chlo hexi- dine and placebo. The ole ance o he ea men om he pa ien s’ and esea che s’ poin o iew had he same punc ua ion on he scale om 1 o 5. �n he s udy g oup, he ole ance was sligh ly be e han in he con ol g oup (Table 4). Mo eo e , in ec ious complica ions we e simila in he expe imen al g oup han in he con ol g oup (Table 5). No s a is ically signi ican di e ences we e ound in any o he wo a iables (p>0.05). Table 1. Cha ac e is ics o he pa ien s included in he s udy. AGE (yea s) SEX TOTAL OF PATIENTS Men Women CHX 0,2% 56.75 ± 6.90 3 1 4 Placebo 63.33 ± 15.89 2 1 3 To al 59.57 ± 10.97 5 2 7 SMOKING HABIT HYGIENIC HABIT No Smoke 10-20 ciga e es  20 ciga e es Ex- Smoke To al 1 Tee h b ushing 2 Tee h b ushing 3 Tee h b ushing To al CHX 0,2% 1 1 0 2 4 0 2 2 4 Placebo 1 1 1 0 3 1 0 2 3 To al 2 2 1 2 7 1 2 4 7 Table 2. Habi s o he pa ien s included in he s udy. Table 3. The in eg i y o he mucosa o he WHO scale o Mucosi is along he s udy. CHX 0,2% Placebo Signi icance 1 2 3 4 5 1 2 3 4 5 1 Week 4(100%) 0(0%) 0(0%) 0(0%) 0(0%) 3(100%) 0(0%) 0(0%) 0(0%) 0(0%) 0.999 2 Week 2(50%) 1(25%) 1(25%) 0(0%) 0(0%) 3(100%) 0(0%) 0(0%) 0(0%) 0(0%) 0.350 3 Week 0(0%) 2(50%) 0(0%) 2(50%) 0(0%) 1(33%) 1(33%) 1(33%) 0(0%) 0(0%) 0.233 4 Week 0(0%) 1(25%) 0(0%) 3(75%) 0(0%) 0(0%) 3(100%) 0(0%) 0(0%) 0(0%) 0.030 5 Week 0(0%) 1(25%) 1(25%) 1(25%) 1(25%) 0(0%) 0(0%) 3(100%) 0(0%) 0(0%) 0.268 6 Week 0(0%) 1(25%) 1(25%) 1(25%) 1(25%) 0(0%) 0(0%) 0(0%) 3(100%) 0(0%) 0.268 7 Week 0(0%) 1(25%) 1(25%) 1(25%) 1(25%) 0(0%) 0(0%) 0(0%) 3(100%) 0(0%) 0.268 8 Week 1(25%) 0(0%) 1(25%) 1(25%) 1(25%) 0(0%) 0(0%) 0(0%) 3(100%) 0(0%) 0.268 9 Week 1(25%) 0(0%) 2(50%) 0(0%) 1(25%) 0(0%) 0(0%) 0(0%) 3(100%) 0(0%) 0.072 10 Week 0(0%) 1(25%) 1(25%) 1(25%) 1(25%) 0(0%) 0(0%) 0(0%) 3(100%) 0(0%) 0.268 11 Week 1(25%) 0(0%) 2(50%) 0(0%) 1(25%) 0(0%) 3(100%) 0(0%) 0(0%) 0(0%) 0.072 Med O al Pa ol O al Ci Bucal. 2015 May 1;20 (3):e378-85. Bioadhesi e chlo hexidine gel and mucosi is e382 Fig. 1. Pain p io o placemen he gel in he s udy g oup han in he con ol g oup. Fig. 2. Pain a he ime o gel applica ion. Med O al Pa ol O al Ci Bucal. 2015 May 1;20 (3):e378-85. Bioadhesi e chlo hexidine gel and mucosi is e383 Discussion This is a epo o a pilo s udy. The calcula ions o he sample ha we e necessa y o ex apola e he da a once hey we e d awn om he s udy sample we e ca ied ou and he o al numbe o pa ien s was calcula ed as 96. Howe e , he au ho s ha e decided no o ad ance in his inal s udy. The easons o his included he e y limi ed e ec i eness (i some a e p esen ) o he d ug used in he s udy g oup (chlo hexidine gel 0.2%) com- pa ed o placebo. Da a om se e al andomized clinical ials show ha chlo hexidine inses do no ha e a majo impac on he p e en ion o mucosi is in pa ien s unde going adio he- apy (18,19). Howe e , i signi ican ly seems o educe o al in lamma ion and ulce a ion in pa ien s unde going chemo he apy. Chlo hexidine inses a e ea men s ha a e applied ac oss he su ace o he o al ca i y wi hou ac ing speci ically on lesions, so he use o chlo hexidi- ne gel would seem o ha e a mo e ad an ageous indi- ca ion o he ea men o inju ies caused by mucosi is because o he localized applica ion (20). �n opposi ion o he ini ial hypo hesis, ou esul s don’ show a clinical imp o emen o he s udy g oup’s pa- ien s. The use o bioadhesi e chlo hexidine gel 0.2% does no educe he equency o mucosi is in he o al ca i y o he pain caused by mucosi is induced by can- ce ea men , and wi h no signi ican di e ences be - ween he pa ien s’ pain be o e and a e he applica ion o i . These esul s a e in ag eemen wi h o he wo k wi h chlo hexidine inse, as in he pape p esen ed by Ru kauskas and Da id (21), who in es iga ed he e ec o chlo hexidine e sus a placebo in pa ien s unde - Fig. 3. Pain one hou a e he applica ion. Pa ien Obse a ion Resea che Obse a ion 1 2 3 4 5 Signi icance 1 2 3 4 5 Signi icance CHX 0,2% 0 1 2 1 0 0.646 0 1 2 1 0 0.646 Placebo 0 0 2 1 0 0 0 2 1 0 Table 4. Tole ance o he ea men om he Pa ien and he Resea che View. INFECTIOUS COMPLICATION NO INFECTIOUS COMPLICATION Signi icance CHX 0,2% 2 (50%) 2 (50%) 0.659 Placebo 2 (66%) 1 (33%) Table 5. �n ec ious Complica ion on he s udy and con ol g oup. Med O al Pa ol O al Ci Bucal. 2015 May 1;20 (3):e378-85. Bioadhesi e chlo hexidine gel and mucosi is e384 going haema opoie ic s em cell ansplan (HSCT) o emission-indica ion chemo he apy. The s udy showed chlo hexidine o be ine ec i e in p e en ing mucosi is. Also, Rae he and colleagues did no suppo he use o chlo hexidine mou hwash o he p e en ion o muco- si is in pa ien s wi h bone ma ow ansplan a ion, and hey ound ha he e was no signi ican di e ence in he se e i y o o al ulce a ion be ween he chlo hexidi- ne and placebo g oups (22-24). Howe e , he e a e s u- dies ha suppo p ophylac ic use o 0.12% chlo hexidi- ne glucona e o educe he equency o o al mucosi is and o al pa hogens in child en wi h Acu e Lymphoblas- ic Leukemia unde going an ineoplas ic chemo he apy (25,26). The p e en i e o al p o ocol using chlo hexi- dine mou hwash can educe bo h he incidence and he se e i y o o al lesions in child en su e ing om leuke- mia ecei ing chemo he apy, acco ding o hese s udies (25). Ne e heless, i can be sugges ed om he da a p e- sen ed he e ha chlo hexidine may play a pa in edu- cing o al damage du ing adio-chemo he apy, possibly h ough plaque con ol and a educ ion in he o al mi- c o lo a (26,27). The e was no di e ence in mucosi is be ween he g oups al hough bac e ial and ungal in ec- ions we e ound sligh ly less o en among he pa ien s using chlo hexidine. Howe e , i canno be ansla ed in o a educ ion in he pain p oduced by mucosi is. The- se esul s a e in acco dance wi h hose published wi h chlo hexidine mou hwash (21). Nowadays, nume ous s udies can be ound abou he ea men o he p e en ion o he mucosi is wi h di e- en p oduc s. Chlo hexidine mou hwash is a common p oduc es ed in he ea men o his illness, and no only in compa ison wi h he placebo. Dodd e al. pu- blished some s udies in which chlo hexidine was com- pa ed wi h s e ile wa e (28) and ano he s udy in which a solu ion o Lidocaine, Benad yl, and Maalox (29) was he objec o compa ison. No di e ences in he se e i y o mucosi is we e ound be ween he g oups in hose s udies. Howe e , he e was a dec ease in he numbe o mic oo ganisms in he CHX g oups compa ed wi h he con ol g oups (30). Chlo hexidine has been also compa ed wi h benzyda- mine hyd ochlo ide o al inses o he p e en ion and ea men o i adia ion mucosi is in pa ien s wi h head and neck cance (3). Signi ican di e ences we e no de- ec ed be ween g oups on ou come measu es; a end has eme ged owa d a lessening o o opha yngeal mucosi- is o pa ien s who ecei ed benzydamine compa ed o pa ien s who ecei ed chlo hexidine (3). Howe e , hese esul s con as wi h hose published by Cheng, who s a- ed ha om he pa ien s’ pe spec i e, chlo hexidine is mo e help ul han benzydamine in educing mucosi is and pallia ing o al discom o (31). O he p oduc s ha e been es ed o he p e en ion and ea men o o al mucosi is like zinc-con aining mou hwash (25) o amine-s annous luo ide solu ion (32). None o hese inses ha e shown clea ad an ages o e chlo hexidine so he e is s ill no ea men o his complica ion o he ea men o head and neck cance . Cu en ly, he e is no e ec i e he apy o esol e o subs an ially imp o e he symp oms o mucosi is al- eady es ablished (9), al hough ecen s udies show ha he use o a low ene gy lase can be a p omising he apy (33,34). � should be poin ed ou ha he esul s o he p esen pilo s udy should be in e p e ed wi h cau ion due o he educed sample size. Ne e heless, i seems ha in ag eemen wi h he e idence indica ing ha chlo hexi- dine inse is no use ul o he p e en ion and ea men o he mucosi is induced by chemo adio he apy o head and neck cance (27,30), he applica ion o gel bioadhe- si e o chlo hexidine wi h he same in en ion has he same use ulness. In ou opinion, u he s udies will be equi ed o ind a ea men di e en om he chlo hexidine ( inse o gel) o mucosi is and imp o e he quali y o li e o pa ien s unde going chemo adio he apy. Conclusions �n his double-blind, andomized pilo s udy, he gel bio- adhesi e o chlo hexidine 0.2% has no p o ided be e clinical esul s han a placebo on pain and discom o in he o al mucosi is caused by chemo adio he apy in he ea men o head and neck cance . Re e ences 1. Posne MR, Haddad R�, Wi h L, No is CM, Goguen LA, Ma- hade an A, e al. �nduc ion chemo he apy in locally ad anced squamous cell cance o he head and neck: e olu ion o he sequen- ial ea men app oach. Semin Oncol. 2004;31:778-85. 2. Qu ob AF, Gue S, Re esz T, Logan RM, Kee e D. P e en ion o o al mucosi is in child en ecei ing cance he apy: a sys ema ic e- iew and e idence-based analysis. O al Oncol. 2013;49:102-7. 3. Kin-Fong Cheng K, Ka Tsui Yuen J. A pilo s udy o chlo hexidine and benzydamine o al inses o he p e en ion and ea men o i - adia ion mucosi is in pa ien s wi h head and neck cance . Cance Nu s. 2006;29:423-30. 4. Bese NS, Hend y J, Je emic B. 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