Table Of Content161
Recent Results
in Cancer Research
ManagingEditors
P.M. Schlag, Berlin (cid:2) H.-J. Senn, St. Gallen
AssociateEditors
P. Kleihues, Lyon (cid:2) F. Stiefel, Lausanne
B. Groner, Frankfurt (cid:2) A. Wallgren, G(cid:2)teborg
FoundingEditors
P. Rentchnik, Geneva
Springer-Verlag Berlin Heidelberg GmbH
U. Reinhold W. Tilgen (Eds.)
Chemosensitivity
Testing
in Oncology
With 75 Figures, Some in Colour,
and 45 Tables
B D
Prof.Dr.UweReinhold
Prof.Dr.WolfgangTilgen
Universit(cid:2)tsklinikendesSaarlandes
HautklinikundPoliklinik
66421Homburg/Saar,Germany
IndexedinCurrentContentsandIndexMedicus
ISBN 978-3-642-62412-4
ISSN0080-0015
LibraryofCongressCataloging-in-PublicationData
Chemosensitivitytestinginoncology/U.Reinhold,W.Tilgen(eds.). p. cm.–
(Recentresultsincancerresearch;161)Includesbibliographicalreferencesandindex.
ISBN 978-3-642-62412-4 ISBN 978-3-642-19022-3 (eBook)
DOI 10.1007/978-3-642-19022-3 1.Cancer–Chemotherapy–Congresses.2.
Drugresistanceincancercells–Congresses.3.Antineoplasticagents–Testing–Con-
gresses.I.Reinhold,Uwe.II.Tilgen,W.(Wolfgang),1944– III.Series.[DNLM:
1. Drug Resistance, Neoplasm – Congresses. 2. Antineoplastic Agents – therapeutic
use–Congresses.3.DrugTherapy–methods–Congresses.QZ267C51582002]
RC271.C5C3972002 616.99'4061–dc21 2002066990
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Preface
Over the past 50 years many in vitro and in vivo drug response
assay systems have been developed to determine the potential ac-
tivityofchemotherapyagents.
The idea was to eliminate ineffective agents and unnecessary
toxic treatment while selecting drugs active in vitro or in the
mouse model that might increase the probability of response in
the patient. None of these test models, however, achieved routine
clinical application in the past. This might be at least in part re-
lated to large discrepancies that were described between the suc-
cessrateoftheassaysystemsandtheclinicalbenefitincancerpa-
tients. The heterogeneity of chemosensitivity that exists between
different tumors as well as between individual tumor lesions may
beoneexplanationforthesefindings.Furthermore,differentassay
endpointssuchasproliferation,metabolism,andvitalitywerede-
veloped to evaluate the effects of cytostatic drugs on tumor cells,
and these might be related to the differing results. However,
knowledgeaboutproceduresforassay-assistedtreatmentselection
hasincreasedrapidlywithinthepastfewyears,andseveralstudies
suggest that test-directed chemotherapy selection now may im-
proveresponseratesandsurvivalinvarioustypesoftumors.
The International Society for Chemosensitivity Testing in On-
cology (ISCO) was founded to promote, coordinate, and improve
clinicalandlaboratory researchinthefieldofpredictivedrugtest-
ing in human tumor cells. In this volume the Proceedings of the
1st ISCO Symposium, held September 14–15, 2001 in Homburg/
Saar,Germany,arepresented.Outstandingresearchersfromdiffer-
ent oncological fields give an overview of the current state of the
artinbasicresearchandclinicalresultsrelatedtothefieldofmul-
tidrug resistance, experimental approaches to drug testing, and
the clinical relevance of individualized chemosensitivity testing in
oncology. The results show that pretherapeutic chemosensitivity
testingisnowemergingasanimportantadjunctinthephysician's
armamentarium.
We wish to thank all the contributors as well as all those who
helpedustoorganizethesymposiumandtoproducethisvolume.
Homburg/Saar,Summer2002 UweReinhold,WolfgangTilgen
Contents
1 In Vitro Drug Testing Methods: Recent Developments
LuminescenceApplicationsforChemotherapeuticDrug
Development .............................................. 3
P.E.Andreotti,G.Caceres,R.Zamkina,M.Dauphin(cid:2)e
TheUseoftheMTTAssaytoStudyDrugResistance
inFreshTumourSamples ..................................... 13
J.M.Sargent
ChemosensitivityTestingofHumanTumorsUsingSi-sensorChips ...... 26
P.Mestres-Ventura
MultiparametricSensorChipsforChemosensitivityTesting
ofSensitiveandResistantTumorCells ........................... 39
A.M.Otto,M.Brischwein,H.Grothe,E.Motrescu,B.Wolf
DevelopmentofNewInVitroChemosensitivityTest
UsingCollagenGelDropletEmbeddedCultureandImageAnalysis
forClinicalUsefulness ....................................... 48
H.Kobayashi
InVitroChemosensitivityTestingofHematologicalCancerPatients:
DetectionofOrnithineDecarboxylase ........................... 62
U.Bachrach,Y.Wang
2 Tumor Chemosensitivity Assays:
Evaluation of In Vitro Results
TheChemosensitivityProfileofRetinoblastoma .................... 73
F.DiNicolantonio,M.Neale,Z.Onadim,J.L.Hungerford,
J.L.Kingston,I.A.Cree
ChemosensitivityTestinginMalignantMelanoma .................. 81
S.Ugurel,W.Tilgen,U.Reinhold
VIII Contents
HumanMelanoma:DrugResistance ............................. 93
H.Helmbach,P.Sinha,D.Schadendorf
Cisplatin,DoxorubicinandPaclitaxelInducemdr1GeneTranscription
inOvarianCancerCellLines ................................... 111
T.Sch(cid:3)ndorf,R.Neumann,C.Benz,M.Becker,
M.Riffelmann,U.-J.G(cid:3)hring,J.Sartorius,
C.-H.W.vonK(cid:3)nig,M.Breidenbach,M.M.Valter,
H.Hoopmann,F.DiNicolantonio,C.M.Kurbacher
3 Clinical Relevance of Tumor-Directed Therapy
ChemosensitivityTestingasanAidtoAnti-CancerDrug
andRegimenDevelopment ................................... 119
I.A.Cree
Assay-AssistedTreatmentSelectionforWomen
withBreastorOvarianCancer ................................. 126
J.P.Fruehauf,D.S.Alberts
ChemosensitivityTestinginGynecologicOncology–
DreamorReality? .......................................... 146
M.Untch,N.Ditsch,E.Langer,C.Kurbacher,C.Crohns,
G.Konecny,S.Kahlert,I.Bauerfeind,H.Hepp
TreosulfanintheTreatmentofMetastaticMelanoma:
FromChemosensitivityTestingtoClinicalTrials .................... 159
K.Neuber
ChemosensitivityTestingandTest-DirectedChemotherapy
inHumanPancreaticCancer .................................. 180
M.Kornmann,H.G.Beger,K.H.Link
ClinicalSignificanceofCellularDrugResistance
inChildhoodLeukemia ...................................... 196
G.J.L.Kaspers,A.J.P.Veerman
ATPChemosensitivityTestinginOvarianandBreastCancer:
EarlyClinicalTrials .......................................... 221
C.M.Kurbacher,O.M.Grecu,U.Stier,T.J.Gilster,
M.-M.Jan(cid:4)t,M.Untch,G.Konecny,H.W.Bruckner,
I.A.Cree
ChemosensitivityTesting–PresentandFutureinJapan ............. 231
T.Kubota,Y.Otani,T.Furukawa,H.Hasegawa,
M.Watanabe,M.Kitajima
SubjectIndex ............................................ 243
Principal Authors
Andreotti,PeterE.,PhD,AtlanticScientificDevelopmentInc.,
PMB46,1511E.CommercialBlvd.,FortLauderdale,FL33334,
USA
Bachrach,Uriel,PhD,DepartmentofMolecularBiologyHebrew
University-Hadassah,MedicalSchool,P.O.Box12272,Jerusalem,
Israel
Cree,IanA.,MD,TranslationalOncologyResearchCentre,
DepartmentofHistopathology,QueenAlexandraHospital,
Portsmouth,PO63LY,UK
Fruehauf,JohnP.,MD,PhD,OncotechInc.,15501RedhillAvenue,
Tustin,CA92780,USA
Kaspers,G.J.L.,MD,DepartmentofPediatricHematology/
Oncology,VUUniversityMedicalCenter,DeBoelelaan1117,
1081Amsterdam,TheNetherlands
Kobayashi,Hisayuki,MD,BiochemicalLaboratory,
NittaGelatinInc.,2-22Futamata,Yao-City,Osaka5810024,Japan
Kornmann,Marko,MD,DepartmentofGeneralSurgery,
UniversityofUlm,Steinh(cid:2)velstraße9,89075Ulm,Germany
Kurbacher,ChristianM.,MD,PhD,DivisionofClinicaland
ExperimentalGynecologicOncology,DepartmentofGynecology
andObstetrics,UniversityofCologneMedicalCenter,
KerpenerStraße34,50931K(cid:2)ln,Germany
Kubota,Tetsuro,MD,FACS,DepartmentofSurgery,Schoolof
Medicine,KeioUniversity,35Shinanomachi,Shinjuku-ku,
Tokyo160-8582,Japan
X PrincipalAuthors
Mestres-Ventura,Pedro,MD,InstituteofAnatomyandCell
Biology,UniversityHospital,UniversityofSaarland,
66421Homburg/Saar,Germany
Neuber,Karsten,MD,DepartmentofDermatology,
UniversityHospitalHamburg,Martinistraße52,20246Hamburg,
Germany
Otto,AngelaM.,MD,Heinz-Nixdorf-ChairforMedicalElectronics,
TechnicalUniversityofMunich,Arcisstraße21,
80290M(cid:3)nchen,Germany
Sargent,JeanM.,MD,HaematologyResearch,PemburyHospital,
TonbridgeRoad,Pembury,Kent,TN24QJ,UK
Schadendorf,Dirk,MD,KlinischeKooperationseinheitf(cid:3)r
Dermatoonkologie(DKFZ)anderUniversit(cid:4)ts-Hautklinik
Mannheim,Universit(cid:4)tHeidelberg,68135Mannheim,Germany
Sch(cid:2)ndorf,Thomas,PhD,DepartmentofGynecologyand
Obstetrics,UniversityofCologne,KerpenerStraße34,
50931K(cid:2)ln,Germany
Ugurel,Selma,MD,DepartmentofDermatology,TheSaarland
UniversityHospital,66421Homburg/Saar,Germany
Untch,Michael,MD,DepartmentofObstetricsandGynecology,
UniversityofM(cid:3)nchen-Großhadern,Marchioninistraße15,
81377M(cid:3)nchen,Germany
1
In Vitro Drug Testing Methods:
Recent Developments
