پماد آلفا

Efficacy of Topical Alpha Oi me (Co ai i g Na u al He a) Compa ed o Topical Hyd oco iso e (1%) i he Heali g of Radia io -I duced De ma i is i Pa ie s wi h B eas Ca ce : A Ra domized Co olled Cli ical T ial

Ma sou A sa i

1Depa me of Radia io O cology, Nemazee Hospi al, Shi az U ive si y of Medical Scie ces, Shi az, I a ;

Fa zi Dehsa a

2S ude Resea ch Commi ee, Depa me of Radia io O cology, Nemazee Hospi al, Shi az U ive si y of Medical Scie ces, Shi az, I a ;

Ahmad Mosalaei

3Shi az I s i u e fo Ca ce Resea ch, Depa me of Radia io O cology, Nemazee Hospi al, Shi az U ive si y of Medical Scie ces, Shi az, I a ;

Shapou Omidva i

1Depa me of Radia io O cology, Nemazee Hospi al, Shi az U ive si y of Medical Scie ces, Shi az, I a ;

Niloofa Ahmadloo

1Depa me of Radia io O cology, Nemazee Hospi al, Shi az U ive si y of Medical Scie ces, Shi az, I a ;

Mohammad Mohammadia pa ah

4Colo ec al Resea ch Ce e , Faghihi Hospi al, Shi az U ive si y of Medical Scie ces, Shi az, I a

Abs ac

Backg ou d: This wo-a m, a domized cli ical s udy aimed o compa e efficacy be wee opical Alpha oi me a d opical hyd oco iso e c eam (1%) i he heali g of adia io -i duced de ma i is i b eas ca ce pa ie s.

Me hods: The i clusio c i e ia comp ised ewly pa hologically p ove , locally adva ced b eas ca ce ( ea ed wi h modified adical mas ec omy followed by seque ial adjuva ea me s, i cludi g ches wall adio he apy 45-50.4 Gy) a d g ade 2 a do 3 ches wall de ma i is. The exclusio c i e ia we e comp ised of a y u de lyi g disease o medica io s i e fe i g wi h he wou d heali g p ocess, p evious his o y of ches wall adio he apy, a d co cu e use of chemo he apy. Six y eligible pa ie s we e a domly assig ed o use ei he opical Alpha oi me (s udy a m, =30) o opical hyd oco iso e c eam (1%) (co ol a m, =30) immedia ely af e eceivi g a o al dose of 45-50 Gy ches wall adio he apy.

Resul s: The mea adia io dose was 49.1 Gy i he co ol a m a d 48.8 Gy i he s udy a m. The mea de ma i is a ea was 13.54 cm2 i he co ol a m a d 17.02 cm2 i he s udy a m. Topical Alpha oi me was mo e effec ive o he heali g of adia io -i duced de ma i is ha was opical hyd oco iso e c eam (1%) (P=0.001). This effec was sig ifica i he seco d week (P=0.007). I addi io , Alpha oi me dec eased he pa ie s’ complai s such as pai (P

Co clusio : Topical Alpha oi me was mo e effec ive o he heali g of adia io -i duced de ma i is ha was opical hyd oco iso e c eam (1%) i ou pa ie s wi h b eas ca ce .

T ial Regis a io Numbe s: IRCT201206099979N1, ACTRN12612000837820

I oduc io

Radio he apy plays a c i ical ole i he ma ageme of b eas ca ce pa ie s. Ove 90% of pa ie s who u de go modified adical mas ec omy fo hei locally adva ced disease equi i g adjuva ches wall adio he apy develop adia io de ma i is. B eas ca ce pa ie s eceivi g ches wall adio he apy develop acu e ski oxici y ( adia io de ma i is) du i g he cou se of adio he apy o a sho pe iod af e he comple io of adio he apy.1,2 Ches wall adia io de ma i is ca dec ease ole a ce fo co i ui g adio he apy, ega ively i flue ce quali y of life, pos po e ea me , a d cause ea me failu e.1 Fo he all he esea ch hi he o co duc ed o he ma ageme of adia io -i duced de ma i is, a co se sus has ye o eme ge as o wha co s i u es he op imal ca e.2

Topical co icos e oids comp ise o e g oup of he sugges ed age s fo he ea me of adia io -i duced de ma i is. Co icos e oids have a i-i flamma o y effec s, which may play a c ucial ole i allevia i g pa ie s’ complai s. Rece evide ce shows he efficacy of opical co icos e oids i his ca ego y.2,3 I addi io , o he local ea me s such as Dexpa he ol, Cale dula, a d ho ey oi me have bee ecomme ded fo ea i g de ma i is.4,5 A o he d ug which has ewly bee i oduced fo he ma ageme of bu i g a d i fec ious wou ds is a u al He a (Lawso ia i e mis li ),6 wi h some i ves iga o s p ovidi g evide ce fo i s a imic obial a d a ioxida p ope ies i wou d heali g as well.7-10 The da a ega di g he efficacy of He a compou ds i he ma ageme of bu a d i fec ed wou ds a e, howeve , i sufficie , a d he e a e o op imal ecomme da io s fo ski ca e i b eas ca ce pa ie s suffe i g adia io de ma i is. This s udy aimed o compa e opical Alpha oi me a d opical hyd oco iso e c eam (1%) i e ms of hei efficacy i he heali g of adia io -i duced de ma i is i b eas ca ce pa ie s u de goi g pos -mas ec omy ches wall adio he apy.

Pa ie s a d Me hods

This s udy is a ope , a domized, co olled, phase II cli ical ial. Eligible pa ie s had ewly pa hologically p ove , locally adva ced b eas ca ce ( ea ed wi h modified adical mas ec omy, followed by seque ial adjuva chemo he apy a d ches wall adio he apy 45-50.4 Gy) a d g ade 2 a do 3 adia io -i duced de ma i is. Exclusio c i e ia co sis ed of a y his o y of collage vascula diseases, diabe es melli us, aki g a y d ugs i e fe i g wi h he wou d heali g p ocess like sys emic s e oids, p evious his o y of ches wall adio he apy, a d co cu e use of chemo he apy. All he pa ie s had o sig he co se fo m befo e pa icipa i g i he s udy. This cli ical ial was app oved by he local Resea ch E hics Commi ee of Shi az U ive si y of Medical Scie ces.

Be wee July 2011 a d Decembe 2011, six y- h ee eligible pa ie s we e a domly assig ed o eceived ei he opical Alpha oi me (s udy a m, =32) o opical hyd oco iso e c eam (1%) (co ol a m, =31) immedia ely af e comple i g pos -mas ec omy ches wall adio he apy wi h a media dose of 45-50 Gy. I addi io , all he pa ie s i bo h a ms we e ecomme ded o pe fo m daily ches wall simple washi g wi h mild soap. Th ee pa ie s we e excluded f om he s udy: o e developed g ade IV de ma i is i he fi s week of i e ve io a d did o mee he i clusio c i e ia, a d wo pa ie s developed seve e pai followi g opical applica io a d decli ed o pa icipa e (figu e 1).

This is a depic io of he CONSORT flow diag am of 60 b eas ca ce pa ie s, who developed ches wall adia io de ma i is

De ma i is g ade was de e mi ed acco di g o he Commo Te mi ology C i e ia fo Adve se Eve s (ve sio 4.0). De ma i is g ade 2 was defi ed as mode a e o b isk e y hema, pa chy mois desquama io mos ly co fi ed o ski folds a d c eases, a d mode a e edema of he i adia ed ches wall. De ma i is g ade 3 was defi ed as mois desquama io i a eas o he ha ski folds a d c eases, bleedi g i duced by mi o auma, o ab asio of he ches wall.11 Radia io po als we e composed of ches wall fields i all he pa ie s a d sup aclavicula , pos -axilla y, a d i e al mamma y fields i mos of hem. Op imiza io of he ski dose o each he p esc ibed o al adia io dose was achieved by ea i g he ches wall fields i all he pa ie s i bo h a ms wi h supe ficial X- ay (120 KV, 10 mA, 2 mm Al fil a io , 4 mm Al half-value laye ) a d wi h a daily f ac io of 1.8-2 Gy (five f ac io s pe week). All he pa ie s had o eceive a o al dose of 45-50.4 Gy. I he co ol a m, opical hyd oco iso e c eam (1%) was used wi h daily washi g of he ches wall a ea; a d i he s udy a m, opical Alpha oi me was used i a simila ma e . De ailed i s uc io s o opical hyd oco iso e c eam (1%) a d opical Alpha oi me we e give o each pa ie as follows: he pa ie s i bo h a ms we e i s uc ed o apply a hi laye of he opical age s wice a day ove he ches wall field, begi i g o he day of he las sessio of adio he apy a d co i ui g eve y day fo 3 weeks. Alpha oi me is a combi a io of Lawso ( a u al He a) a d u sa u a ed fa y acids. Lawso is he mai compo e of Alpha oi me ex ac ed f om Lawso ia i e mis. All of he pa ie s we e followed up fo 3 weeks af e developi g adia io de ma i is. Du i g his pe iod, each pa ie was exami ed eve y week. De ma i is g ade, pa ie s’ age, b eas ca ce s age, a d de ma i is a ea (cm2) we e eco ded i ou da a shee befo e he comme ceme of i e ve io . Subseque ly, he de ma i is a ea (cm2) was measu ed i depe de ly by 2 physicia s i each exami a io u il 3 weeks af e he s a of i e ve io . I egula de ma i is a ea was es ima ed i each pa ie usi g a g id pape . The pa ie s’ complai s, i cludi g ski bu i g, pai , a d p u i us, a d amou of ski discha ge cha ge we e sco ed f om 0 o 3 i ou da a shee i each exami a io (subjec ive sco es we e defi ed as: 0: o complai ; 1: mild; 2: mode a e; a d 3: seve e complai ). I his s udy, he a e of de ma i is heali g was he objec ive c i e io . The p ima y e d poi of he s udy was he speed of de ma i is heali g. De ma i is heali g was defi ed as comple e e-epi helializa io of mois desquama io (de ma i is g ades 2 a d 3) a eas. The heali g a e of de ma i is (g ades 2 a d 3) was measu ed by compa i g he a e of he dec ease i he de ma i is a ea (cmweek) be wee he s udy a d co ol a ms. The mea de ma i is a ea (cmweek) was compa ed be wee he s udy a d co ol a ms du i g 3 co secu ive weeks of i e ve io . A mi imum sample size equi ed 24 pa ie s i each a m o e su e 80% powe a he 5% sig ifica ce level fo de ec i g a 40% imp oveme i he heali g a e f om 30% o 70%.

The da a we e a alyzed usi g s a is ical es s. The Chi-squa e es was employed o compa e he da a pe ce ages a he begi i g of he ea me such as age, adio he apy dose, a d s age of disease. The Ma Whi ey es was used o compa e he cha ges i he pa ie s’ complai s such as pai a d p u i us. A d, he es wi h Bo fe o i co ec io was used o compa e bu a ea de ma i is by SPSS (ve sio 17.0) a d o compa e he cli ical measu eme s a d he cli icopa hological cha ac e is ics be wee he ial a ms. A P value less ha 0.05 was co side ed s a is ically sig ifica .

Resul s

The e was o mea i gful diffe e ce i e ms of baseli e va iables, i cludi g age, **7**, de ma i is g ade, o al adia io dose, disease s age, a d de ma i is a ea (cm2) be wee he wo a ms. The mea age of he co ol a d s udy a ms was 47 ( a ge=25-72) yea s a d 49 ( a ge=28-81) yea s, espec ively. The mea adia io dose was 49.1 Gy ( a ge=45-50.4 Gy) i he co ol a m a d 48.8 Gy ( a ge=45-50.4 Gy) i he s udy a m. The mea de ma i is a ea (summa io of g ades 2 a d 3) was 13.54 ( a ge=0.5-75.0) cm2 i he co ol a m a d 17.02 ( a ge=0.7-78.0) cm2 i he s udy a m ( able 1). All he pa ie s i bo h a ms ole a ed he opical ea me s well, a d o sys emic o local eac io o de ma i is agg ava io was obse ved. The a alysis of da a showed ha 3 weeks’ use of opical Alpha oi me wice a day was mo e effec ive o he heali g of adia io -i duced de ma i is ha ha of opical hyd oco iso e c eam (1%) (P=0.001). This effec was sig ifica i he seco d week (P=0.007); howeve , his diffe e ce was o sig ifica fo g ade 2 de ma i is (P=0.343). This effec was also sig ifica o he heali g of g ade 3 de ma i is (P=0.003) du i g 3 weeks of i e ve io (figu e 2, able 2). Fu he mo e, he heali g of bo h g ade 2 a d g ade 3 de ma i is was sig ifica i he seco d week of ea me (P=0.027 a d P=0.004, espec ively). Rega di g he pa ie s’ subjec ive complai s, al hough he e was o s a is ically sig ifica diffe e ce i bu i g se sa io be wee he wo a ms ove he 3-week i e ve io pe iod (P=0.078), Alpha oi me dec eased he pa ie s’ o he complai s such as pai (P

Table 1

Dis ibu io of baseli e va iables be wee he s udy a d co ol a ms a he begi i g of i e ve io

RT: Radio he apy

The a e of de ma i is heali g ime du i g 3 co secu ive weeks of ea me is illus a ed he e

Table 2

Ra e of de ma i is heali g du i g 3 co secu ive weeks of ea me

Table 3

Pa ie s’ elief of complai s du i g 3 co secu ive weeks of ea me

Discussio

Locally adva ced b eas ca ce accou s fo a co side able po io of all b eas ca ce s, pa icula ly i developi g cou ies such as I a . Nea ly all pa ie s wi h locally adva ced b eas ca ce eed o eceive adio he apy as a esse ial pa of hei local ea me .1,12 Pos -mas ec omy adio he apy ca i evi ably lead o deg ees of de ma i is, affec i g he pa ie s’ life quali y. Radia io -i duced de ma i is may be acu e o ch o ic. Acu e adia io de ma i is p ese s as ski pai , e y hema, edema, d y o we scali g, discha ge, p u i us, ulce a io , bleedi g, a d ec osis.1,2 These sig s a d symp oms usually peak a o e o 3 weeks followi g he las adia io sessio a d elieve wi hi 3-6 weeks of he comple io of adio he apy i d y desquama io . Neve heless, i cases wi h mois desquama io (g ades 2 a d 3), i is p olo ged o 4-6 weeks. This acu e de ma i is ca cause empo a y o eve comple e adia io i e up io .1-4,13 I he p ese s udy, acu e de ma i is was maximized i he seco d week i he s udy a m a d i he hi d week i he co ol a m.

I his s udy, he g ades of de ma i is we e de e mi ed acco di g o he Commo Te mi ology C i e ia fo Adve se Eve s (ve sio 4.0).11 These sco i g c i e ia a e based o visual i spec io . This objec ive measu eme assesses he ski oxici y ega dless of he pa ie fac o s i flue ci g he deg ee of adia io de ma i is. Yamazaki e al.14 evalua ed he effec of pa ie fac o s o adia io de ma i is i pa ie s wi h b eas ca ce who u de we pos ope a ive adio he apy af e b eas -co se vi g su ge y. They compa ed ski colo cha ges (usi g a objec ive a alyze ) be wee ea ed a d co ala e al o mal b eas s a d fou d mo e eddish a d highe deg ees of adia io de ma i is i heavie pa ie s. Diffe e assessme me hods have bee d aw upo i o he s udies.15 Yoshikawa e al.16 assessed he deg ee of adia io de ma i is by compa i g se ial ski cha ge i pho og aphs. I he cu e s udy, he p ima y e d poi was he a e of wou d heali g be wee he s udy a d he co ol a m; he efo e, he assessme me hod was o a impo a issue.

The e a e va ious ea me - ela ed a d pa ie - ela ed fac o s affec i g he deg ee of adia io de ma i is. A y ype of ece o old damage due o su ge y, bu , o lesio s ca po e ia e adia io de ma i is. O he pa ie - ela ed fac o s i clude his o y of collage vascula diseases, diabe es melli us, e al failu e, olde age, a d co cu e use of immu osupp essive o chemo he apeu ic age s. The si e of adio he apy, adia io field size, o al dose of adia io , dose pe f ac io , a d ype a d e e gy of adia io a e co side ed as ea me - ela ed fac o s affec i g he deg ee of adia io de ma i is.17

The e is o co se sus ega di g he op imal ea me o p eve io fo adia io de ma i is. Be ha as i may, some suppo ive ca e, i cludi g ge le washi g wi h mild soap, wea i g loose co o clo hi g, avoidi g ex eme empe a u es, avoidi g su exposu e o adia io fields, avoidi g shavi g o hai emoval i adia io fields, a d avoidi g use of a y u p ove opical age s like cosme ic p oduc s, is ge e ally advised fo all pa ie s u de goi g adio he apy.1,2,4,14

I he li e a u e, a wide va ie y of opical age s such as co icos e oids, Aloe Ve a, Biafi e c eam, hyalu o ic acid, Suc alfa e, Dexpa he ol, a d vi ami E have bee used i acu e adia io -i duced de ma i is. No e heless, he exis i g evide ce is i sufficie o ecomme d he use of a specific opical age o p eve o o ea his complica io .1-4,17,18 The efo e, sys ema ic eviews sugges ha he efficacy of he age s a d app oaches should be compa ed i phase I a d II cli ical ials.2,17

O e of he p oposed ea me s fo adia io -i duced de ma i is is he use of opical co icos e oids. A i-i flamma o y effec s of hese age s may play a impo a ole i elievi g pa ie s’ symp oms.1-4,17,18 Some evide ce i dica es he mois u izi g effec s of hyd oco iso e c eam as he likely mecha ism i he heali g of adia io -i duced de ma i is. Mois u iza io plays a esse ial ole i he ea ly p eve io of acu e de ma i is. Acco di g o his mecha ism, hyd ophilic age s such as Aloe Ve a gel o vege able oil educe he seve i y of adia io de ma i is as well as opical hyd oco iso e.13,19 The e is o clea evide ce o suppo he supe io i y of po e co icos e oids ove hyd oco iso e i he li e a u e. I a s udy, Clobe aso e bu y a e caused mo e seve e adia io eac io s compa ed o hyd oco iso e wi h simila p esc ibed adia io doses.20 I a o he s udy, Schmu h e al.18 compa ed he opical c eam of hyd oco iso e (1%) a d he opical c eam of Dexpa he ol (0.5%) i he heali g of acu e adia io -i duced de ma i is; howeve , hey fou d o sig ifica diffe e ce i de ma i is heali g be wee he wo ea me a ms. O he local ea me s such as Dexpa he ol, Cale dula, a d ho ey oi me have bee used fo he ea me of de ma i is i diffe e s udies.1,2,4,17,21 A o he d ug which has ewly bee i oduced fo he ma ageme of bu a d i fec ious wou ds is a u al He a (Lawso ia i e mis li ), as was used i ou s udy i he fo m of “Alpha oi me ”.7-10 Ma y of oday’s mode d ugs have hei o igi i adi io al pla medici e. Alpha oi me is a combi a io of Lawso ( a u al He a) a d u sa u a ed fa y acids. Lawso is he mai compo e of Alpha oi me ex ac ed f om Lawso ia i e mis. U sa u a ed fa y acids i Alpha oi me have a a i-i flamma o y ole.13 The e is some evide ce suppo i g he safe y a d efficacy of a u al he a i wou d heali g.8,10,22-24 I a s udy co duc ed by Gu ja Guha e al.7 a ioxida effec s of He a de iva ives we e p oved. I a a imal s udy, Nayak e al.8 demo s a ed he wou d heali g ac ivi y of a u al he a usi g excisio , i cisio , a d dead space wou d models. Philip Jacob e al.9 i ece s udy fou d a ioxida a d scave gi g ac ivi y of He a de iva ives. I addi io , Hosei i e al.10 showed fu he effec ive ess of Alpha oi me (He a-bea i g oi me ) i compa iso wi h opical silve Sulfadiazi e i g ade 3 bu wou ds i fec ed by Pseudomo as ae ugi osa. Yucel a d Guzi 24 obse ved he efficacy a d safe y of a u al He a i ea i g ha d-foo sy d ome i 10 pa ie s wi h colo a d b eas ca ce followi g chemo he apy wi h Capeci abi e alo e o combi ed wi h Doce axel. I ou s udy, opical Alpha oi me (co ai i g a u al he a) was mo e effec ive o he heali g of adia io -i duced de ma i is ha was opical hyd oco iso e c eam (1%) i he seco d week of i e ve io . I addi io , Alpha oi me sig ifica ly dec eased he pa ie s’ complai s such as pai , p u i us, a d discha ge compa ed o opical hyd oco iso e c eam (1%).

He a is a i expe sive a u al pla age wi h a i-i flamma o y, a ipy e ic, a d a algesic effec s. I also plays a a ioxida a d immu omodula o y ole a d lacks he po e ial acu e a d la e adve se effec s of co icos e oids.24,25

To da e, he e has bee o eco ded s udy i ves iga i g he efficacy of Alpha oi me i he heali g of acu e adia io -i duced de ma i is. The cu e s udy had some limi a io s i e ms of ime a d fi a cial issues. The sample size was small a d he le g h of pa ie s’ follow-up was limi ed.

Co clusio

Acco di g o he esul s of his s udy, h ee weeks’ use of opical Alpha oi me was mo e effec ive o he heali g of adia io -i duced de ma i is ha was opical hyd oco iso e c eam (1%) i ou b eas ca ce pa ie s. Fu he evalua io wi h la ge umbe s of pa ie s is sugges ed fo he co fi ma io of hese p elimi a y esul s.

Ack owledgme

This cli ical ial was app oved a d suppo ed by Shi az U ive si y of Medical Scie ces ( esea ch p ojec umbe 90-P-2764). This ma usc ip is pa of a hesis by Fa zi Dehsa a. This s udy was suppo ed by Shi az U ive si y of Medical Scie ces. The au ho s would like o ha k he Cli ical Resea ch Developme Depa me of Nemazee Hospi al fo s a is ical co sul a io a d edi o ial assis a ce.

Co flic of I e es : No e decla ed.