Selenium for alleviating the side effects of chemotherapy, radiotherapy and surgery in cancer patients

29 Pages·2009·0.31 MB·English

Selenium for alleviating the side effects of chemotherapy,
radiotherapy and surgery in cancer patients (Review)
Dennert G, Horneber M
ThisisareprintofaCochranereview,preparedandmaintainedbyTheCochraneCollaborationandpublishedinTheCochraneLibrary
2009,Issue2
http://www.thecochranelibrary.com
Seleniumforalleviatingthesideeffectsofchemotherapy,radiotherapyandsurgeryincancerpatients(Review)
Copyright©2009TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAINLANGUAGESUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
AUTHORS’CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
CHARACTERISTICSOFSTUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
DATAANDANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
WHAT’SNEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
CONTRIBUTIONSOFAUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
DECLARATIONSOFINTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
SOURCESOFSUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
INDEXTERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Seleniumforalleviatingthesideeffectsofchemotherapy,radiotherapyandsurgeryincancerpatients(Review) i
Copyright©2009TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
[InterventionReview]
Selenium for alleviating the side effects of chemotherapy,
radiotherapy and surgery in cancer patients
GabrieleDennert1,MarkusHorneber2
1Medizinische Klinik 5, Klinikum Nord, Nuernberg, Germany. 2Medizinische Klinik 5 - Schwerpunkt Onkologie/Haematologie,
KlinikumNord,Nuernberg,Germany
Contactaddress:GabrieleDennert,MedizinischeKlinik5,KlinikumNord,Prof.-Ernst-Nathan-Str.1,Nuernberg,D-90419,Germany.
[email protected].(Editorialgroup:CochranePain,PalliativeandSupportiveCareGroup.)
CochraneDatabaseofSystematicReviews,Issue2,2009(Statusinthisissue:Newsearchforstudiescompleted,conclusionsnotchanged)
Copyright©2009TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
DOI:10.1002/14651858.CD005037.pub2
Thisversionfirstpublishedonline:19July2006inIssue3,2006.
Lastassessedasup-to-date: 16February2009.(Helpdocument- DatesandStatusesexplained)
This record should be cited as: Dennert G, Horneber M. Selenium for alleviating the side effects of chemotherapy, radio-
therapy and surgery in cancer patients. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD005037. DOI:
10.1002/14651858.CD005037.pub2.
ABSTRACT
Background
This isan updated version of the original Cochrane review publishedin Issue 3, 2006. Seleniumsupplementsare frequentlyused
by cancer patients. Selenium is an essential trace element and is involved in antioxidant protection and the redox-regulation in
humans.Severaladverseeffectsofradiotherapyandchemotherapyincancerpatientsaswellascellularprocessesthatmaintainchronic
lymphoedemahavebeenlinkedtooxidativecellprocessesinthehumanbody.Seleniumhasbeenclaimedtoalleviatesideeffectsof
conventionalcancertherapyandrecentlybeeninvestigatedasaremedyagainstchemotherapyandradiotherapy-associatedsideeffects
andsecondarylymphoedema.
Objectives
Thisreviewassessedtheeffectsofsupplementaryseleniumonadverseeffectsofconventionalradiotherapy,chemotherapy,orsurgery
inoncologypatientsandonqualityoflife/performancestatusduringandafteroncologicaltreatment.
Searchstrategy
The Cochrane Pain, Palliative & Supportive Care Trials Register, the Cochrane Database of Systematic Reviews, the Database of
AbstractsofReviewsofEffects(DARE),CENTRAL,MEDLINE,EMBASE,SIGLE,Cancerlit,CCMed,theGermanonlineregister
forcancertrials,theISRCTN,themRCT,theNCIClinicalTrialsregisterdatabasesweresearchedandmostupdatedinJuly2007.
Selectioncriteria
Randomisedcontrolledtrials(RCTs)ofseleniummono-supplementsincancerpatientsundergoingtumourspecifictherapy,suchas
chemotherapy,radiotherapyorsurgery.
Datacollectionandanalysis
Tworeviewauthorsindependentlycheckedtrialsforeligibility,extracteddataandassessedtrialquality.
Mainresults
Onenewincludedstudyaswellasfurtherparticipantstoastudyalreadyincludedwasaddedtothisupdateinvolvingafurther39
participants.Therewereatotalofthreestudiesincludedinvolving162participantsforthisupdate.
Seleniumforalleviatingthesideeffectsofchemotherapy,radiotherapyandsurgeryincancerpatients(Review) 1
Copyright©2009TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
ForthisreviewtwoRCTswereincludedinvestigatingsecondarylymphoedemain60womenafterbreastcancersurgeryand20menand
womenafterheadandneckcancersurgery.Oneongoingtrialwithpreliminaryresultsof82participantswasalsoidentifiedstudying
radiotherapyinduceddiarrhoeaasasecondaryoutcome.Allstudieshadconsiderabledrawbackswithregardstoqualityandreporting.
Onestudyonsecondarylymphoedemareportedadecreasednumberofrecurrenterysipelainfectionsintheseleniumsupplementation
groupcomparedtoplacebo.Thesecondstudyreportedadecreasedfacialswellingintheseleniumgroupinatwo-weekperiodfollowing
surgicaltumourresection.However,resultsmustbeinterpretedwithcautionandcannotbegeneralisedtootherpopulations.
Theongoingtrialonradiotherapyassociateddiarrhoeapreliminarilyreportedalowerincidenceofdiarrhoeainparticipantsreceiving
seleniumsupplementationconcomitanttopelvicradiation,however,nodatawerepresented.Wemustawaitpublicationoffinalresults
todiscussthesefindingsindetail.
No RCTs were found studying the effect of selenium supplementation on other therapy-associated toxicities or quality of
life/performancestatusincancerpatients.
Authors’conclusions
Thereisinsufficientevidenceatpresentthatseleniumsupplementationalleviatesthesideeffectsoftumourspecificchemotherapyor
radiotherapytreatmentsorthatitimprovestheafter-effectsofsurgery,orimprovesquality-of-lifeincancerpatientsorreducessecondary
lymphoedema.Todate,researchfindingsdonotprovideabasisforanyrecommendationinfavouroragainstseleniumsupplementation
incancerpatients.Potentialhazardsofsupplementingatracemineralshouldbekeptinmind.Sincethelastversionofthisreview,the
onenewadditionalstudyhasnotprovidedinformationtochangetheconclusionsoftheoriginalreview.
PLAIN LANGUAGE SUMMARY
Seleniumsupplementsforalleviatingthesideeffectsofchemotherapy,radiotherapyandsurgeryincancerpatients
Thereisnoevidencethatseleniumsupplementsreducesideeffectsofchemotherapy,radiotherapyortheeffectsofsurgeryincancer
patients.Seleniumisamineralnecessaryforhumanhealth.Seleniumactsagainstcelldamageinthebodyandmighthelptoalleviate
thesideeffectsoftherapiesincancerpatients,suchasnausea,diarrhoeaorthelymphretentioninlimbs.Seleniumsupplementsare
frequentlyusedbycancerpatients.Thissystematicreviewlookedatstudiesprovidingseleniumsupplementstocancerpatientsand
found no clearevidence thatseleniumsupplementsimprove side effectsof cancer therapy.Noadverse effectswere reportedin the
studies, but evidence of overdosing, allbe itunintentional andseleniumintoxication hasoccurredinseveralseleniumusers. More
researchisneededtofindoutwhichdosesofseleniumsupplementscanbereasonablyusedbycancerpatientsandwhetherselenium
supplementscanaffectthesideeffectsofcancertherapy.
BACKGROUND
nistsforpreventionofchemotherapyandradiotherapyassociated
ThisreviewisanupdateofapreviouslypublishedreviewinThe sideeffects.
CochraneDatabaseofSystematicReviews(Issue3,2006)on’Se-
Acutemucositisisasevereconditionseenfrequentlyinpatients
leniumforalleviatingthesideeffectsofchemotherapy,radiother-
undergoingradiotherapy.Arecentreviewfoundthatabout80%
apyandsurgeryincancerpatients’.
ofENTradiotherapypatientsdevelopedmucositis,abouthalfof
Seleniumisanessentialtraceelementforhumans.Itisinvolved themexperiencedasevereform(gradethreetofour)whichleadto
in antioxidant protection and redox regulation as a component treatmentinterruptionoralterationinoneinninepatients(Trotti
ofseleno-proteinsandasasourceofseleno-metabolites(Hatfield 2003).Patientsundergoingpelvicradiationfore.g.gynecological
2001).Adverseeffectsofradiotherapyandchemotherapyincan- malignanciesareatriskfordevelopingacuteintestinalmucositis,
cerpatientshavebeenlinkedtotheformationoffreeradicalsand enteritis, and diarrhoea. Atrophy of the salivary glands and xe-
therelatedoxidativedamagetonormalcells(Weijl1997).Lately, rostomiaarelong-termsequelaeofaradiogenicsialadenitisafter
interventionstrategieshavebeeninvestigatedtousebiologicalre- ENTradiotherapy,whichcanonlybecontrolledinsufficientlyby
sponsemodifiers,suchasseleniumcompounds,astoxicityantago- symptomaticinterventions,suchassalivasubstitutesorstimulants
Seleniumforalleviatingthesideeffectsofchemotherapy,radiotherapyandsurgeryincancerpatients(Review) 2
Copyright©2009TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
(Groetz2003). OBJECTIVES
Bothinacuteandlong-termsideeffectsofradiotherapy,selenium Theaimofthisreviewwastoassesstheeffectsofsupplementary
has been discussed as a preventive agent. In vitro experiments selenium,givenatanydose,on:
foundacytoprotectiveeffectofsodiumseleniteonhumanfibrob-
• adverse effects of conventional radiotherapy, chemo-
lastsandendothelialcellswithoutreducingradiotherapyactivity
therapy,and/oroncologicalsurgery;
againstcancercells(Rodemann1999;Schleicher1999).Sagowski
2004 showed that administration of parenteral sodium selenite • qualityoflifeandperformancestatusduringandafter
reducedradiogenicdamage toparotidglandsinrats,whichwas conventionaloncologicaltherapy.
confirmedbybetterglandfunctionafterirradiation.
Afurtheraimwastomakerecommendationsforfutureresearch.
Anumberofchemotherapytoxicitiesandadverseeffectshavebeen
linkedtotheformationoffreeradicalsbycytostatics(Weijl1997).
A protective effect of ebselen against doxorubicin induced cell
METHODS
damagewasseeninratcardiomyocytesinvitro(Kotamraju2000).
Animalstudiessuggestedthatsodiumselenitemaydecreasecis-
platininducednephrotoxicity(Baldew1989;Francescato2001;
Criteriaforconsideringstudiesforthisreview
Yoshida2000)andmyelotoxicity(Ohkawa1988)inratsandmice.
Cardiacsensitivitytoischemiaafteradriamycintreatmentwasre-
ducedbysodiumselenitesupplementationinrats(Boucher1995).
Typesofstudies
Secondary lymphoedema is a common complication after sur- Randomised-controlledtrials(RCTs)wereincludedinthisreview
gical and radiological therapy of breast and ENTcancer (Dietz which studied the efficacyof seleniumsupplementation assup-
1998;Erickson2001).Patientswithlymphoedemaoftheupper plementarycancertreatment.Norestrictionwasmaderegarding
extremity and the head and neck region can experience a sub- publicationstatus,yearorlanguageofpublication.
stantialdegreeoffunctionalimpairmentandpsychologicalmor-
bidity.Endolaryngealoedemaandswellingmayevenleadtoair- Typesofparticipants
way obstruction andrequiretracheostomy.Thedevelopmentof Studyparticipantswerepatientsofanyagewithmalignantdiseases
oedemaisindicatedbysurgicalorradiologicaldamagetothelym- (regardlessofthestageofdisease)whowereundergoingtumour
phaticsystemresulting influidretention (Zimmermann2005). specifictherapy(chemotherapy,radiotherapyorsurgery).
Higherinterstitialpressurelessensoxygensupplytooedematous
tissueandchronicinflammatoryprocessesleadtofibrosisofsmall
Typesofinterventions
lymphvessels.Highly reactive oxygen containing radicals (reac-
Studiesthatassessedseleniumsupplementsorseleniumprepara-
tiveoxygenspecies)areclaimedtohaveacrucialroleindevelop-
tionsatanydose,duration,androuteofadministrationcompared
mentand maintenance of lymphoedema.Seleniumcompounds
withplaceboornointervention/routinecarewereeligible.Studies
mayimproveredoxbalanceinsparselyperfusedoedematoustis-
usingseleniumsupplementsaspartofamulticomponentprepa-
sueand,hence,beeffectiveincontrolandtherapyofsecondary
rationinwhichtherewasnostudyarmtestingforseleniumsup-
lymphoedema(Micke2003;Zimmermann2005).
plementsalonewerenotincludedinthisreview.Collateralinter-
Theroleofthecomplementaryuseofseleniumincancerpatients ventions(e.g.manualtherapyforlymphoedema)wereallowedif
isunclear.Somepublicationsreportapositiveeffectofselenium adequatelycontrolledfor,andusedin,allarmsofthestudy.
supplementation on radio/chemotherapy associated side effects
andlymphoedemafollowingsurgicalcancertreatment.However, Typesofoutcomemeasures
trialevidenceisinconsistent,andasystematicreviewonthistopic Dataonthefollowingoutcomeswerecollected:
hasnotbeenconducted.
• theeffectofseleniumontheincidenceandseverityof
SurveysinCanada,UK,AustriaandGermanyfoundthatfourto chemotherapyorradiotherapyrelatedtoxicitiesifthey
12%ofbreastcancerandprostatecancerpatientsusedselenium werereportedaccordingtointernationallyacceptedcri-
supplementsduringandaftercancertherapytoalleviateadverse teriaforcommontoxicities(e.g.WHO,ECOGorNIH
effects of conventional therapy and to improve quality of life ( criteriaforadverseeffects;DCTD2004;Miller1981;
Cheetham2001;Nam1999;Petru2001;Sehouli2000).Thishigh Oken1982);
numberofcancerpatientsusingseleniumsupplementscontrasts • the effect of selenium on the incidence and severity
withthelittleclearevidenceinthisfieldthusjustifyingtheneed oflymphoedemafollowingsurgicaltreatmentorradio-
toupdatethisCochranereview. therapy;
Seleniumforalleviatingthesideeffectsofchemotherapy,radiotherapyandsurgeryincancerpatients(Review) 3
Copyright©2009TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
• patient-reportedlevelsofphysicalandpsychologicalin- We contacted the Chinese Cochrane Center and the Russian
dicesofsymptomdistress(measuredusingreliableand Branch of the Nordic Cochrane Center, but due to limited re-
validassessmenttools); sourceswewerenotabletohavetheMoscowMedicalLibraryor
• qualityoflife,asmeasuredbyavalidatedinstrument; theChineseBiomedicalDatabasesearchedforpublications.
• incidenceandtypeofadverseeffects. Additionally,wecheckedthereferencelistsofretrievedpublica-
tions for further studies and searched the archive of our work
group. Manufacturers of selenium supplements and authors of
publications were contacted and asked to contribute additional
Searchmethodsforidentificationofstudies
data.
Electronicsearches
Datacollectionandanalysis
Forthisupdatewesearchedthefollowingdatabases,sourcesofgrey
literature and registers of clinical trialswith the reportedsearch
strategies: Selectionofstudies
Identifiedpublicationswerecheckedforeligibilitybybothreview
• theCochranePain,Palliative&SupportiveCareTrials authors.Apublicationwasobtainedinfulltextifitcouldnotbe
Register(July2007), rejectedwithcertaintyonthebasisof itstitleorabstract. Stud-
• the Cochrane Database of Systematic Reviews (The iesofpossiblerelevancewerealsoobtainedinfulltextforfurther
CochraneLibrary,Issue2,2007), evaluation. If inclusion or exclusion could notbe assessedfrom
• theDatabaseofAbstractsofReviewsofEffects(DARE) thepublicationalone,firstauthorswerecontactedforadditional
(TheCochraneLibrary,Issue2,2007), information.Reasonsforexcludingtrialsfromthereviewarere-
• the Cochrane Central Register of Controlled Trials portedinthe’Characteristicsofexcludedstudies’table.
CENTRAL(TheCochraneLibrary,Issue2,2007), Thereviewauthorswerenotblindedtoauthors´ names,institu-
• MEDLINE(1966toJuly2007), tionandsourceofpublication.Anydisagreementwasresolvedby
• EMBASE(1980to2007week28), discussionbetweenthereviewauthors.
• SIGLE(October2004;databasediscontinuedin2005),
• Cancerlit(July2007),
Dataextractionandmanagement
• CCMed(ClinicalContentsinMedicine,German)(Oc-
Both review authors independently extracted and documented
tober2004),
• theGermanonlineregisterforcancertrials(July2007), datausingapre-testedextractionform.Thefollowinginformation
• the International Standard Randomised Controlled wascollected:
TrialNumberRegisterISRCTN(October2004), • study methods (randomisation, allocation conceal-
• theMeta-RegisterofControlledTrialsmRCT(October ment,blinding,eligibilitycriteria,follow-up);
2004), • participants(patientcharacteristics,age,gender,cancer
• theNCIClinicalTrialsregister(October2004). type,othercancermanagement/treatment,comorbid-
ity)andadditionaltreatments/medication;
Thesearchfortheoriginal review wasrunin2004, subsequent • interventions (selenium dose, regimen, duration of
searchesfor theupdate wererunin 2007. CCMed database -a treatment,routeofadministration)andplacebo
databaseofGermanjournals-searchwasomittedin2007asthe • outcomemeasures;
relevantjournalsforthisreviewarenowindexedinMEDLINE, • studywithdrawals,drop-outsandprotocoldeviations;
whichtheywerenotin2004.ISRCTN,mRCTandNCIClinical • adverseeffects;
Trialsareonlineregistersforclinicalstudiesandhelpfultoidentify • informedconsent,ethicboardapproval.
ongoing RCTs.Weconsideredatimeintervalofthreeyearstoo
Discrepancies were resolved by discussion between both review
shortfor an update searchin these online resourcestaking into
authors.
accountareasonablebalanceofresourcesandexpectedoutcome.
We contacted all primary study authors of included studies for
WeusedtheMEDLINEsearchstrategyasoutlinedinAppendix
additionalinformationanddata.Detailsofalleligiblestudiesare
1 (via PubMed - 1966 to July 2007), its strategy was adapted
summarisedinthe’Characteristicsofincludedstudies’table.
anddevelopedforotherdatabasessearchedwhichcanbeseenin
Appendix2.
Methodologicalquality
Reviewauthorsassessedstudiesformethodologicalqualityusing
Searchingotherresources
acriticalappraisalchecklistaccordingtoJuni2001.
Seleniumforalleviatingthesideeffectsofchemotherapy,radiotherapyandsurgeryincancerpatients(Review) 4
Copyright©2009TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Thischecklistincludedthefollowing aspectsof methodological theinclusioncriteriaofthisreview,afurther30papers(represent-
quality: ing26studies)hadtobeexcluded.Themainreasonsforexclusion
werethatthepublications describedanon-randomised studyor
• randomisation,allocationconcealment,
the study investigated laboratory parameters, e.g. the change of
• blinding,
serumseleniumstatusaftersupplementation.(see’Characteristics
• specificationofeligibilitycriteria,
ofexcludedstudies).
• equal provision of care (apart from selenium supple-
The remaining eight publications represented four studies (
mentation)andequalfollow-up,
Büntzel 2004; Kasseroller 1998; Mücke 2007; Zimmermann
• similarityofgroupsatbaseline,
2005). Two of these studies were completed (Kasseroller 1998;
• reportingofprotocoldeviations,withdrawalsanddrop-
Zimmermann2005)andintermediateresultshavebeenpublished
outs,
foroneoftheongoingstudies(Mücke2007)(see’Characteristics
• reportingofoutcomemeasuresandadverseeffects,
ofincludedstudies’).Onestudyisongoing(Büntzel2004)andno
• statisticalprocedures(intention-to-treatanalysis).
preliminaryresultshavebeenpublishedsofar.Allstudyauthors
Additionally,completedstudieswereratedaccordingtotheOx- werecontactedandprovidedadditionalpapersorinformationfor
ford Quality Scale (Jadad 1996) and the Delphi list (Verhagen thisreview.
1998). AllfourstudieswereorarebeingconductedinGermanyandAus-
tria as a cooperation between different clinicians and one Ger-
manpharmaceuticalcompany,whichmanufacturessodiumselen-
Analysis
iteproductsforclinicalapplication.
Weplannedtocalculateasummary statistic andits95%confi-
denceinterval(CI)foreachoutcomeandtoperformameta-anal-
Includedstudies
ysisofsummarystatisticsifappropriate.Duetothesmallnumber
ofincludedstudies,theirmethodologicallimitationsandclinical
heterogeneity,weconsideredsummarystatisticsnottobeappro-
1)Effectsontheincidenceandseverityoflymphoedema
priate.Studyresultsarereportedaspresentedintheoriginalpub-
licationalongwithinformationonadverseeffects. Two completed RCTs could be identified for this outcome (
Kasseroller1998;Zimmermann2005):
Kasseroller 1998 was described as a placebo-controlled ran-
domised,doubleblindtrial.Sixtyfemalecancerpatientswerein-
cluded in the study and results were presented for 57. The ob-
RESULTS
jectivewastoinvestigatetheefficacyofsodiumseleniteapplica-
tion in combination with physical therapy to relieve secondary
lymphoedemasafterbreastcancersurgery;recurrenceoferysipela
Descriptionofstudies infection in the oedematous limb was reported as the primary
outcome.Participantsintheinterventiongroupreceivedsodium
See:Characteristicsofincludedstudies;Characteristicsofexcluded
selenite per os for 15 weeks with a sum dose of 19.600 µg to
studies;Characteristicsofongoingstudies.
28.000 µg(19.6mgto28mg,dependingonbody weight).All
participants were treated with a combined physical congestion-
Resultsofthesearch
reliefprogramme.
For this update review one new included study (Zimmermann Preliminary results of this study were published in 1996 giving
2005) was included and more participants were added to the datafor34femalecancerpatients,including25womenafterbreast
Mücke2007 studyadding afurther39participantstothetotal cancersurgeryandninewomenafterpelvicsurgery.Accordingto
participantsincludedwithinthereview.Thepreviousreviewiden- ourcorrespondencewiththeauthor,all25breastcancerpatients
tifiedanongoingstudywhichhasbeencompletedsincetheorig- reportedin1996wereparticipantsofthislaterstudy(Kasseroller
inalpublicationofthisreviewandisnowexcluded(Schumacher 1998). We could not obtain additional information on the re-
2003). The total number of participants considered within the mainingparticipantswithothergynecologicmalignancies.
includedstudiesis162. Zimmermann2005wasalsodescribedasaplacebo-controlledran-
Oursearchreturned1981studiesofpossiblerelevance.Ofthese, domised,double-blindtrial.Twentyparticipants(18male,twofe-
1943studiescouldbeexcludedbasedontitleorabstract.Theap- male)withhead-and-neckcancerundergoingcurativelyintended
parentlyhighnumberofscreenedstudieswasduetoourintensive tumourresectionwereincluded.Theobjectivewastoinvestigate
literaturesearchindatabasesthatdidnotallowtheuseofasearch bloodseleniumconcentrationanddifferentenzymeactivitiesand
strategyotherthanthemaintopic“selenium”.Afterscreening,the postoperative lymphoedema. Only the latter outcome is of in-
remaining 38publications wereobtained infulltext.Following terestforthissystematicreview. Participantsintheintervention
Seleniumforalleviatingthesideeffectsofchemotherapy,radiotherapyandsurgeryincancerpatients(Review) 5
Copyright©2009TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
groupreceived3000µgsodiumseleniteintravenouslyontheday
ofsurgeryand1000µgsodiumselenitedaily(i.v.orperos(p.o.))
ondaysoneto21aftersurgery.
2)Effectsontheincidenceandseverityofchemo-or
radiotherapyrelatedtoxicities
Oneongoing RCT with published preliminary resultscould be
identifiedforthisoutcome:
Mücke2007investigatedtheuseofsodiumselenitesupplements
infemalecancerpatientsduringadjuvantradiotherapyinanon-
goingrandomised,unblindedtwo-armedmulti-centerstudywith
a no-treatment control group. Study objectives were the assess-
mentoftheefficacyofsodiumselenitep.o.fornormalizationof
seleniumdeficiencyduringadjuvantradiotherapy(primaryout-
come)and,secondarily,itseffectontheincidenceandseverityof
radiotherapytoxicities(e.g.diarrhoeaaccordingtocommontox-
icity criteria(CTC), changesin body weightand blood count).
Theinterventiongroupreceivedasumdosageofapproximately
15,900to18,000µgsodiumselenitep.o.(15.9to18mg)during
radiotherapy(ca.5weeks).Accordingtothestudyprotocol,the
trialwillrandomise200participantstointerventionandcontrol
group. Intermediate results have been published for 41 partici-
pants (Mücke 2004b) and 63 participants (Mücke 2004a), 77
participants(Mücke2006b),79participants(Mücke2006a),80
participants (Micke 2007), and 82 participants (Mücke 2007a;
Mücke2007b)(Mücke2007).
Riskofbiasinincludedstudies
Detailsofthemethodologicalqualityofincludedstudiesaregiven
inanadditionaltable(seeAdditionalTable1:’QualityAssessment
ofIncludedStudies’).
Table1. Qualityassessmentofincludedstudies
Study Allocation Conceal- Study Eligibility Blinding Attrition Delphilist Jadad Comment
ment groups score
Kasseroller randomal- unclear no infor- eli- patient: 3dropouts 1-0-0-1-1- 1-1-1 Selection
1998 location; mation gibilitycri- yes; care 1-1-0-0 bias possi-
method of on compa- teria speci- provider: ble: alloca-
sequence rabil- fied; num- yes; out- tion con-
gen- ityofstudy ber of el- come as- cealment
erationnot groups re- igible pa- sessor:yes- unclear,no
reported garding tients not un- infor-
riskfactors stated blindingof mation on
atbaseline treatment distribu-
status after tionofrisk
Seleniumforalleviatingthesideeffectsofchemotherapy,radiotherapyandsurgeryincancerpatients(Review) 6
Copyright©2009TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Table1. Qualityassessmentofincludedstudies (Continued)
end of in- factors at
tervention baseline.
Observer/detection
bias possi-
ble:
no control
procedure
reported
whether
blinding
was suc-
cessful,de-
tails on
outcome
assess-
ment not
reported
Performance
bias pos-
sible: con-
comi-
tant treat-
ment not
sufficiently
described
Mücke randomal- serially no infor- eli- patient: dropouts / -- -- Prelimi-
2007 location; numbered, mation gibilitycri- no; care with- nary
method of sealed, on compa- teria speci- provider: drawals results of
sequence opaqueen- rabil- fied; num- no; out- not anongoing
gen- velopes ityofstudy ber of el- come as- reported study
erationnot groups re- igible pa- sessor:no inmostre- (Delphi
reported garding tients not centpubli- List
riskfactors stated cations and Jadad
atbaseline Score will
be given
when final
report is
available)
Selection
bias un-
likely, but
pos-
sible: allo-
cationcon-
Seleniumforalleviatingthesideeffectsofchemotherapy,radiotherapyandsurgeryincancerpatients(Review) 7
Copyright©2009TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Table1. Qualityassessmentofincludedstudies (Continued)
ceal-
ment ade-
quate, but
no infor-
mation on
distribu-
tionofrisk
factors for
outcome.
Observer/detection
bias possi-
ble: no
blinding.
Perfor-
mancebias
possible:
concomi-
tant treat-
ment un-
clear
randomal- unclear no infor- eli- pa- no 1-0-0-1-0- 1-1-1 Selection
Zimmermannlocation; mation gibilitycri- tient: un- dropouts 0-0-0-0 bias possi-
2005 method of on compa- teria speci- clear; care or with- ble: alloca-
sequence rabil- fied; num- provider: drawals tion con-
gen- ityofstudy ber of el- un- cealment
erationnot groups re- igible pa- clear; out- unclear,in-
reported garding tients not come as- formation
riskfactors stated sessor: un- on distri-
atbaseline clear bution of
riskfactors
atbaseline.
Observer/detection
bias possi-
ble: study
was
reportedas
double-
blinded
- informed
consent
form,how-
ever, con-
tained in-
forma-
Seleniumforalleviatingthesideeffectsofchemotherapy,radiotherapyandsurgeryincancerpatients(Review) 8
Copyright©2009TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.