Table Of ContentP
harmacotherapy
C
of achexia
© 2006 by Taylor & Francis Group, LLC
P
harmacotherapy
C
of achexia
Edited by
Karl G. Hofbauer
Stefan D. Anker
Akio Inui
Janet R. Nicholson
Boca Raton London New York
A CRC title, part of the Taylor & Francis imprint, a member of the
Taylor & Francis Group, the academic division of T&F Informa plc.
© 2006 by Taylor & Francis Group, LLC
Published in 2006 by
CRC Press
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© 2006 by Taylor & Francis Group, LLC
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International Standard Book Number-10: 0-8493-3379-2 (Hardcover)
International Standard Book Number-13: 978-0-8493-3379-8 (Hardcover)
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Library of Congress Cataloging-in-Publication Data
Pharmacotherapy of cachexia / edited by Karl G. Hofbauer.
p. ; cm.
Includes bibliographical reverences and index.
ISBN 0-8493-3379-2 (alk. paper)
1. Cachexia--Chemotherapy. I. Hofbauer, Karl G. [DNLM: 1. Cachexia--drug therapy. 2.
Cachexia--etiology. 3. Cachexia--physiopathology. WB 146 P536 2005]
RB150.C33P43 2005
616’.047--dc22 2005051075
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© 2006 by Taylor & Francis Group, LLC
Preface
Cachexia is an underestimated and frequently neglected medical condition.
Although it is regarded as an independent risk factor for morbidity and mortal-
ityitdoesnotreceivesufficientmedicalattentionandtreatment. Thetherapyof
cachexia requires a coordinated, flexible, and multidisciplinary approach. Since
neithernutritionaltherapynorphysicalexerciseissufficienttotreatcachexia,phar-
macotherapyplaysanimportantrole.Awidevarietyofdrugswithhighlydiverse
mechanisms of action is currently being used but for many of them convincing
evidenceoftherapeuticefficacyislackingandtheirbenefit/riskratioisunknown.
The present book was conceived with the aim of providing a comprehens-
ive reference source for health care professionals concerned with the treatment
of cachexia. It is organized in six sections; the first one dealing with the patho-
physiology of cachexia, the second with the diseases associated with cachexia,
andthethirdwithgeneraltherapeuticaspects.Thesubsequentthreesectionsare
devotedtopharmacotherapy.Asectionondrugsinclinicaluseisfollowedbyone
on drugs in research and development and a final section, which is focused on
futuredevelopments.
Whyshouldareaderinterestedincachexiaconsultabookinsteadofreadingthe
latestreviewsorresearcharticles?Theeditorsstronglybelievethataheterogeneous
syndromesuchascachexiaanditsdiversetreatmentoptionscanbebestpresented
inasinglevolumewherecontributionsbydifferentauthorsonvariousaspectscan
befoundandcompared.Suchabroadrangeofchaptersallowsthereadertofind
informationaboutvariousdifferentaspectsofthediseaseanditstreatmentandto
selectthemostpertinentaspectsrelatingtohisspecificquestionbyusingasingle
referencesource.
We are grateful to the numerous internationally recognized specialists who
have contributed chapters on various aspects of cachexia. Through their critical
evaluation of pathophysiological mechanisms, clinical features, and therapeutic
optionsthisbookprovidesthereaderwithavaluablesourceofinformationonall
aspectsofthisseriousandlife-threateningsyndrome.Wewouldalsoliketothank
the publishers for their expert editorial advice and particularly acknowledge the
excellent support of Jny Wittker who was responsible for all administrative and
organizationalworkthroughoutthepreparationofthisvolume.
KarlG.Hofbauer
StefanD.Anker
AkioInui
JanetR.Nicholson
© 2006 by Taylor & Francis Group, LLC
Editors
KarlG.HofbauerholdsthechairforappliedpharmacologyattheMedicalFaculty
of the University of Basel, Switzerland. He received his M.D. degree from the
University of Vienna, Austria, and specialized in experimental pharmacology at
theUniversityofHeidelberg,Germany.Hespentmorethan20yearsinpreclinical
drugresearchatCiba,laterNovartis,whereheheldseveralresearchmanagement
positionsintheareaofcardiovascularandmetabolicdiseases.Hehascontinuedto
workonthesesubjectsaftermovingbacktoacademiaattheBiozentrum,Basel.His
bookPharmacotherapyofObesity: OptionsandAlternativespublishedbyCRC
Pressin2004isnowcomplementedbythepresentvolumeonthepharmacotherapy
ofcachexia.
AkioInuiisprofessorofinternalmedicineintheDepartmentofBehavioralMedi-
cine,KagoshimaUniversityGraduateSchoolofMedicalandDentalSciences.He
holds a doctoral degree from Kobe University School of Medicine. Dr. Inui has
focusedontranslationalresearchofpeptidesinbodyweightregulationdisorders
includingobesity,cancercachexia,andeatingdisorders.
Dr.InuireceivedtheJanssenAwardoftheAmericanGastroenterologicalAsso-
ciation in 2004. He is the editor of Peptides, Nutrition, International Journal
of Oncology, Current Nutrition and Food Science, and Recent Patents on CNS
DrugDiscovery.Hisresearcheffortisnowdirectedatelucidatingtheroleofthe
ghrelin-neuropeptideYpathwayfromstomachtobraininappetiteandgutmotility
regulation.
StefanD.AnkerisprofessorofappliedcachexiaresearchintheCharitéCampus
Virchow-Klinikum in Berlin, Germany (since 2002). He also has an academic
appointmentattheDepartmentofClinicalCardiologyattheNationalHeartand
LungInstitute(NHLI),ImperialCollegeSchoolofMedicineinLondon,England.
Dr.AnkerstudiedmedicineandobtainedhisM.D.(1993)fromCharitéMedical
SchoolinBerlin.HewentontoearnaPh.D.(1998)atImperialCollegeLondon,
basedonstudiesoncachexiainchronicheartfailure.Aspartofhistraining,Dr.
Anker was a cardiology research fellow and a senior research fellow and team
leaderattheNHLI.
The recipient of numerous clinical research awards and grants, Dr. Anker
is also a prodigious writer and has more than 160 original papers, reviews, and
editorialstohiscredit.Hispublishedworkaddressesissuesinthepathophysiology
and treatment of chronic heart failure, specifically the prognostic importance of
© 2006 by Taylor & Francis Group, LLC
Editors
weight loss (i.e., cachexia) and the effect of treatments to prevent and reverse
cardiaccachexia.Additionally,heisactiveinimmunologicalresearchandrecently
hasextendedhisworktocachexiainotherchronicillnesses,likeCOPDandcancer.
Asanadjuncttohiswritingendeavors, Dr. Ankerservesontheeditorialboards
oftheJournalofCardiacFailure,ItalianHeartJournal,InternationalJournalof
Cardiology,andZeitschriftfürKardiologie.Dr.Ankerismemberofinternational
steeringcommitteesoffiveclinicaltrialsinheartfailure.
Janet R. Nicholson is a post-doctoral research fellow at the Biozentrum, Uni-
versityofBasel, Switzerland. ShereceivedherPh.D.inpharmacologyfromthe
UniversityofCambridge,UKin1998andthenmovedtotheUSAtocompletea
3-yearpost-doctoralresearchfellowshipattheUniversityofMichigan,whereshe
worked on central mechanisms involved in the regulation of energy balance. In
hercurrentposition,Dr.Nicholson’sworkfocusesoninvivomodelsofcachexia,
andsheisactivelyinvolvedinadrugdiscoveryprogramaimingtoidentifynovel
pharmacologicalinterventionsforthetreatmentofcancercachexia.
© 2006 by Taylor & Francis Group, LLC
Contributors
StefanD.Anker AntonioL.C.Campos
CampusVirchow-Klinikum DepartmentofGastrointestinal
Berlin,Germany Surgery
FederalUniversityofParana
JonasAxelsson Curitiba,Parana,Brazil
KarolinskaInstitutet
KarolinskaUniversityHospitalat PaulV.Carroll
Huddinge Guy’s&St.Thomas’NHS
Stockholm,Sweden FoundationTrust
London,UK
WaldemarBanasiak
CardiacDepartment TommyCederholm
MilitaryHospital KarolinskaInstitutet
Wroclaw,Poland KarolinskaUniversityHospitalat
Huddinge
VickieE.Baracos Stockholm,Sweden
UniversityofAlberta
Edmonton,Alberta,Canada AndrewL.Clark
CastleHillHospital
ShehzadBasaria Cottingham,Hull,UK
JohnsHopkinsUniversitySchoolof
Medicine RossG.Clark
Baltimore,Maryland,USA TercicaInc.
SouthSanFrancisco,California,USA
KasparBerneis
MedicalUniversityClinic AndrewJ.S.Coats
HospitalBruderholz UniversityofSydney
Bruderholz,Switzerland Sydney,Australia
MarijkeBrink JulioC.U.Coelho
UniversityofBasel DepartmentofGastrointestinal
DepartmentofResearch Surgery
UniversityHospital FederalUniversityofParana
Basel,Switzerland Curitiba,Parana,Brazil
© 2006 by Taylor & Francis Group, LLC
Contributors
LauraA.Coleman K.C.H.Fearon
MarshfieldClinicResearch TheUniversityofEdinburgh
Foundation Edinburgh,UK
Marshfield,Wisconsin,USA
DavidJ.Glass
RegeneronPharmaceuticals
M.Dahele
Tarrytown,NewYork,USA
ClinicalandSurgicalSciences
SchoolofClinicalSciencesand
CarolinaG.Goncalves
CommunityHealth
DepartmentofSurgery
TheUniversityofEdinburgh
SUNYUniversity
Edinburgh,UK
Syracuse,NewYork,USA
MellarP.Davis LindseyHarle
TheHarryR.HorvitzCenterfor UniversityofTexasMedicalBranch
PalliativeMedicine atGalveston
TaussigCancerCenter Galveston,Texas,USA
TheClevelandClinicFoundation
OlofHeimbürger
Cleveland,Ohio,USA
KarolinskaInstitutet
KarolinskaUniversityHospitalat
AmieJ.Dirks
Huddinge
WingateUniversitySchoolof
Stockholm,Sweden
Pharmacy
Wingate,NorthCarolina,USA
KarlG.Hofbauer
AppliedPharmacologyBiozentrum
AdrianS.Dobs
UniversityofBasel
DivisionofEndocrinologyand
Basel,Switzerland
Oncology
JohnsHopkinsUniversitySchoolof AkioInui
Medicine KagoshimaUniversityGraduate
Baltimore,Maryland,USA SchoolofMedicalandDental
Sciences
WolframDoehner Kagoshima,Japan
CharitéMedicalSchool
EwaA.Jankowska
Berlin,Germany
MilitaryHospital
Wroclaw,Poland
WilliamJ.Evans
UniversityofArkansasforMedical
AminahJatoi
Sciences
MayoClinic
LittleRock,Arkansas,USA
Rochester,Minnesota,USA
ClaudineFalconnier MatthiasJohn
UniversityHospital UniversityHospitalCharité
Basel,Switzerland Berlin,Germany
© 2006 by Taylor & Francis Group, LLC
Contributors
UlrichKeller JanetR.Nicholson
UniversityHospital AppliedPharmacologyBiozentrum
Basel,Switzerland UniversityofBasel
Basel,Switzerland
CharlesP.Lambert
SmithaPatiyil
UniversityofArkansasforMedical
Sciences MayoClinic
LittleRock,Arkansas,USA Rochester,Minnesota,USA
SimonaPerboni
ChristiaanLeeuwenburgh
DepartmentofMedicalOncology
UniversityofFlorida
UniversityofCagliari
CollegeofMedicine
Cagliari,Italy
Gainesville,Florida,USA
PiotrPonikowski
BengtLindholm
CardiacDepartment
KarolinskaInstitutet
MilitaryHospital
KarolinskaUniversityHospitalat
Wroclaw,Poland
Huddinge
Stockholm,Sweden PhilipA.Poole-Wilson
NationalHeartandLungInstitute
GiovanniMantovani FacultyofMedicine
DepartmentofMedicalOncology ImperialCollege
UniversityofCagliari London,UK
Cagliari,Italy
StefaniePossekel
DanielL.Marks SantheraPharmaceuticalsLtd.
OregonHealth&SciencesUniversity Liestal,Switzerland
Portland,Oregon,USA
AbdulRashidQureshi
KarolinskaInstitutet
MichaelM.Meguid
KarolinskaUniversityHospitalat
DepartmentofSurgery
Huddinge
SUNYUniversity
Stockholm,Sweden
Syracuse,NewYork,USA
MarkusA.Ruegg
ThomasMeier
Biozentrum
SantheraPharmaceuticalsLtd.
UniversityofBasel
Liestal,Switzerland
Basel,Switzerland
JohnE.Morley AnnemieM.W.J.Schols
SaintLouisUniversitySchool DepartmentofRespiratoryMedicine
ofMedicine UniversityofMaastricht
St.Louis,Missouri,USA Maastricht,TheNetherlands
© 2006 by Taylor & Francis Group, LLC
Contributors
R.J.E.Skipworth YoshiyukiTakimoto
SchoolofClinicalSciencesand TheUniversityofTokyo
CommunityHealth Tokyo,Japan
TheUniversityofEdinburgh
Edinburgh,UK ErgunY.Uc
CollegeofMedicine
PeterStenvinkel
UniversityofIowa
KarolinskaInstitutet
IowaCity,Iowa,USA
KarolinskaUniversityHospitalat
Huddinge
KatrinUtech
Stockholm,Sweden
MedicalUniversityClinic
HospitalBruderholz
SabineStrassburg
Bruderholz,Switzerland
DepartmentofCardiologyCharité
CampusVirchow-Klinikum
Berlin,Germany StephanvonHaehling
NationalHeart&LungInstitute
SusumuSuzuki DepartmentofClinicalCardiology
SUNYUniversity ImperialCollegeSchoolofMedicine
Syracuse,NewYork,USA London,UK
© 2006 by Taylor & Francis Group, LLC
