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

Abstract

Background: To evaluate, in an initial way, the effectiveness of bioadhesive chlorhexidine gel 0.2% versus placebo as a preventive and therapeutic intervention of oral mucositis induced by radiation therapy and chemotherapy in patients diagnosed with head and neck cancer treated with chemoradiotherapy. Material and Methods In this pilot study, 7 patients (range of age: 18- 65), having histological documented diagnosis of squamous carcinoma on the head and neck region in stage III and IV, and receiving combined radiation treatment and chemotherapy (cisplatin 100 mg/m2 IV on days 1, 22, and 43 of irradiation) were studied. Simultaneously, a topical application was performed with bioadhesive chlorhexidine gel 0.2% in the study group, and the placebo gel for the control group in 5 applications per day, from the time of initiation of cancer treatment to 2 weeks after completion of chemo-radiotherapy treatment (11 weeks of follow-up). The gradation of mucositis, pain, analgesic consumption, infectious complications, and treatment tolerance was measured. Results. After 7 patients completed the protocol, any differences were observed between groups in an interval analysis. Mucositis, pain, and tolerance was similar in both groups. Conclusions: Our results must be interpreted with caution due to the reduced sample size, but the use of bioadhesive chlorhexidine gel 0.2% didn’t contribute clinical improvement to the oral mucositis induced by radiation therapy and chemotherapy.

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

Author: Díaz Sánchez, Rosa María; Pachón Ibáñez, Jerónimo; Marín Conde, Fátima; Rodríguez-Caballero, Ángela; Gutiérrez Pérez, José Luis; Torres-Lagares, Daniel
Publisher: Medicina Oral
Year: 2015
DOI: 10.4317/medoral.20338
Source: https://idus.us.es/bitstreams/03faaf2a-9899-4139-bc83-1d787109c0e6/download
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
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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
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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
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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.

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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 .
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