October 15, 1992

CancerResearchOFFICIAL JOURNAL OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH

VOLUME 52 •¿�NO. 20 •¿�PP 5575-5852ISSN 0008-5472 •¿�CNREA 8

8TH INTERNATIONAL SYMPOSIUMON PREVENTION AND DETECTION OFCANCERCOFACTOR

INTERACTIONSAND CANCERPREVENTIONMarch

17-19, 1993 Nice,Franceisrm

A í> ^ <hl 3tC®Callfor Abstracts

Deadline: December 7,(992•Assessinginteracting tumor promoting effects of genetic,hormonal.aging,

oncogene amplification, tumor suppressor genes.•¿�Focuson metabolic activation of carcinogens,disorders in signaltransduction,clinical and laboratory identification of risk and prognosis, exposureassessmentand intermediate endpoints. •¿�Insightsin effectivenessofcancer detection measures,intervention strategies, chemopreventiontrials, risk reductioneducation.Speakers:

K Alitalo, University Roland;P Boyle. European School Oncology;W Cavane«,University California SanDiego; R Flamant,Institute GustaveRoussy,H Fujiki, National Cancer Center ResearchInstitute Japan;RA Good, University South Rorida; MR Henderson, University Washington;LE Holm, Karolinska Hospital; J Morton. Albany Medical College; AB Miller.University of Toronto; R Montesano, International Agency ResearchCenter.1Penn.University Cincinnati; F Perora,Columbia University; HC Pitot,University Wisconsin; EM Smith. University Iowa; MR Spitz, University TexasMD Anderson Cancer Center TT Sun.Chinese Academy Medicine; H Vainio.International Agency ResearchCancer J Wahrendorf. German CancerResearchCenter IB Weinstein, Columbia University. D Zaridze. CancerResearchCenterRussia.For

Information and AbstractForms:USA-Phone (508)-856-1822, Fax (508)-856-1824

Mme S Kay, UMMC. Box 20, 55 LakeAvenue North, Worcester MA 01655FRANCE: Phone (33-93) 817133x2514,Fax (33-93) 533512Mme F Fein, CAL 36 Voie Romaine.F-06054Nice CedexPRECEDING

THE 8TH INTERNATIONAL SYMPOSIUMON PREVENTION AND DETECTION OFCANCERGENETIC

FACTORS IN PREDICTIVEAND PREVENTIVEONCOLOGYMarch

14-16, 1993 Nice,FranceLAtffr-

LSPÖLIGUECall

for AbstractsDeadline: December 7,1992•

Advances in molecular biology that highlight relevant insight into normalgene regulation and effects of gene mutations on cell kinetics anddifferentiation in cancer development including molecular markers of riskand prognosis, cofactors, polygenetk diseases,and identification ofoncogenesand tumor suppressor genes.•¿�Appraisal of data on geneticpredisposition to cancer, epigenetic influences,gene transfer trials, signaltransduction, mukidrug resistance,genetics of metastasisand hereditaryaspectsof thyroid, breast, colorerai, rymphoid, CMS and othertumors.Speakers:

JFBach,Necker Hospital; A Baimain,CRC Beatson Institute forCancer Research;J Bernard, French Consultative Committee on Ethics inLife Sciences;JL Biedler. Memorial Sloan-Kettering Cancer Center, H deThe, Hospital St Louis; T Dryja, MassachusettsEyeEar Infirmary;M Feldman,Weizmann Institute Science;CC Harris, National CancerInstitute USA;JR Idle, University Newcastle Upon Tyne; P Kourilsky,Institute Pasteur.GM Lenoir, International Agency ResearchCancer.HT Lynch, Creighton University School Medicine; MM Mareel, UniversityGhenc R Montesano. International Agency ResearchCancer JJMule,National Cancer Institute USA; C Mullen. National Cancer Institute USA;M Perricaudet, Institute Gustave Roussy,BAJPonder, UniversityCambridge; G Rouleau,McGill University, F Sigaux.Hospital St Louis;P Tambourin, Institute Curie; G Thomas, Institute Curie; HFA Vasen,University HospitalUtrechtFor

Information and AbstractForms:USA:Phone (508)-856-l822, Fax (508)-856-1824

Mme S Kay, UMMC, Box 20, 55 Lake Avenue North, Worcester MA 01655FRANCE:Phone (33-93) 817133x2514,Fax (33-93) 533512Mme F Fein, CAL 36 Voie Romaine,F-06054 Nice Cedex

p53 monoclonal antibodies.-12-1

DO71801240

... on extensive panelofp53 antibodiesoptimized to yieldclean, consistentresults in routinelyprocessed and frozensections.

CM 1 polyclonal

A broad range of monoclonal antibodies against prognostic markers areavailable for use in routinely processed and frozen tissues. For extensivetechnical literature and a free guide to prognostic marker research, pleasecall (800)421 4149.

4600 Morris Canyon Rd.San Ramon, CA 94583Tel (510) 275-0550FAX (510) 275-1999

BioGenex GmbH (Germany)(49) 8165 4040BioGenex KK (Japan)(81) 03 3448 0875

PROLEUKIN" (Aldesleukm)

Brief Summary ot Prescribing InformationFor tuli prescribing information, see Package Insert.

WARNINGSPROLEUKIN*(aidesleukmforinjection)shouldbeadministeredonlymahospitalsellingunderthesupervisionol aqualifiedphysicianexperiencedmIneuseofanti-canceragentsAnintensivecarelacihlyandspecialistsskilledincardio-puimonaryorintensivecaremedicinemusibeavailable

PROLEUKINadministrationhasbeenassociatedwithcapillaryleaksyndrome(CIS)CISresultsin hypotensionandreducedorganperfusionwhichmaybesevereandcanresultindeath

TherapywithPROLEUKINshouldberestrictedto patientswithnormalcardiacandpulmonaryfunctionsasdefinedbythalliumstresstestingandformalpulmonaryfunctiontestingExtremecautionshouldbeusedin patientswithnormalthalliumstresstestsandpulmonaryfunctiontesiswhohaveahistoryolpriorcardiacorpulmonarydisease

PROLEUKINadministrationshouldbeheldmpatientsdevelopingmoderaleloseverelethargyorsomnolence,continuedadministrationmayresultmcoma

INDICATIONS AND USAGEPROLFUKIN(aldesleukm)is indicatedlortheIreatmenloladults(¿18yearsol age)withmeiastaticrenalcellcarcinoma

Carelulpatientselectionismandatorypriorto theadministrationof PROLEUKINSee"CONTRAINDICATIONS,""WARNINGS"and"PRECAUTIONS"Sectionsregardingpatientscreening,includingrecommendedcardiacandpulmonaryfunctiontestsandlaboratorytesis

Evaluationof clinicalstudiesto dalerevealsthatpatientswithmorelavoratileECOGperformancestatus(ECOGPS0) al treatmentinitiationrespondbeltertoPROLEUKIN.with a higherresponseraleand lowerloxiciiy(See"CLINICALPHARMACOLOGY"Section"Clinical Experience"Subsectionm Packageinsert)Therefore,selectionof patientstortreatmentshouldincludeassessmentolperformancestatus,asdescribedmTableI inPackageInsert

ExperiencempalieniswithPS>1isextremelylimited

CONTRAINDICATIONSPROLEUKIN{aldesleukm)is contrabdicatedm patientswitha knownhistoryolhypersensitivitylo inlerleukm-2oranycomponentol thePROLEUKINformulation

PatientswithanabnormalIhalhumstresslesior pulmonaryfunctiontestsareexcludedfromtreatmentwithPROLEUKINPatientswithorganallograftsshouldbeexcludedas well In addition,relrealmenfwithPROLEUKINis contramdicatedinpatientswhoexperiencedthefollowingloxicitieswhilereceivinganearliercourseoltherapy

•¿�Sustainedventriculartachycardia(25 beats)•¿�Cardiacrhythmdisturbancesnoicontrolledorunresponsivelomanagement•¿�RecurrentchestpainwithECGchanges,consistentwithangina

ormyocardialinfarction•¿�Intubationrequired-U hours•¿�Pericardia!lamponade•¿�Renaldyslunchonrequiringdialysis>72hours•¿�Comaorlonepsychosislasting>48hours•¿�Repetitiveorditlicul!tocontrolseizures•¿�Bowelischemia/perforation•¿�Glbleedingrequiringsurgery

WARNINGSSeeDoxed"WARNINGS"PROLEUKIN(aldesleukm)administrationhasbeenassociatedwithcapillaryleak

syndrome(CLS)whichresultsIromextravasationol plasmaproteinsandHuidintoineextravascularspaceandlossol vasculartoneCLSresultsmhypotensionandreducedorganperfusionwhichmaybesevereandcanresultmdeathTheCLSmaybeassociatedwithcardiacarrhythmias(supravenIncularandventricular),angina,myocardialmlarction.respiratorymsulliciencyrequiringmtuDaiiongastrointestinalbleedingorinfarction,renalmsulliciency,andmentalstatuschanges

Becauseof InesevereadverseeventswhichgenerallyaccompanyPROLEUKINtherapyal therecommendeddosages,ihoroughclinicalevaluationshouldtoeperformedtoexcludeIromIreatmenlpatientswithsignificantcardiac,pulmonary,renal,hepaticorCNSimpairment

Shouldadverseeventsoccur,whichrequiredosemodification,dosageshouldbewithheldratherthanreduced(See"DOSAGEANDADMINISTRATION"Section."Dosi Modificilion" SubsectionmPackageInsert)

PROLEUKINmayexacérbalediseasesymptomsmpatientswithclinicallyunrecognizedor untreatedCNSmétastasesAllpatientsshouldhavethoroughevaluationandIreatmenlol CNSmétastasesprior lo receivingPROLEUKINtherapyTheyshouldbeneuroiogicaiiystablewithanegaliveCTscanInaddition,extremecautionshouldbeexercisedin treatingpatientswitha historyol seizuredisorderbecausePROLEUKINmaycauseseizures

IntensivePROLEUKINtreatmentis associatedwithimpairedneulrophilfunction(reducedcnemotaxis)andwithanincreasedriskol disseminatedinfection,includingsepsisandbacterialendocarditis,mtreatedpatientsConsequently,pre-existingbaclenafmlectionsshouldbeadequatelytreatedpriorto initiationo! PROLEUKINiherapyAdditionally,allpatientswithindwellingcentrallinesshouldreceiveantibioticprophylaxiseffectiveagainstS aureusAntibioticprophylaxiswhichhasbeenassociatedwilh a reducedincidenceol slaphylococcalinfectionsm PROLEUKINstudiesincludestheuseol oxacilhn.nalcillm.ciprofloxacm,or vancomycmDisseminatedinfectionsacquiredmthecourseol PROLEUKINtreatmentareama¡orcontributorlo treatmentmorbidityanduseotantibioticprophylaxisandaggressivetreatmentol suspectedanddocumentedinfectionsmayreducethemorbidityatPROLEUKINtreatmentNOTE:Prior to tha usi of anyproducimentionedinthis paragraph,the physicianshouldrafar to the packageInsert tor therespectiveproduct.

PRECAUTIONSGeneralPatientsshouldhavenormalcardiac,pulmonary,hepaticandCNSfunc-ttonal thestariol therapyPatieniswhohavehadanephreclomyarestilleligiblelortreatmentit theyhaveserumcrealmmelevels515mg/dl

Adverseeventsarefrequent,oltenserious,andsometimeslataiCapillaryleaksyndrome(CLS)beginsimmediatelyalterPROLEUKINtreatment

startsandis markedby increasedcapillarypermeabilityto proteinandfluidsandreducedvascularlone Inmostpatients,thisresultsmaconcomitantdropin meanarterialbloodpressurewithin2to12hoursaftertheslarlol IrealmentWithcontinuedtherapy,clinicallysignificanthypotension(definedassystolicbloodpressurebelow90 mmHrj or a 20 mmHg droptrombaselinesystolicpressure)andhypopertusionwill occurIn addition,extravasationof proteinandfluidsintotheexlravascuiarspacewill leadtoedemaformationandcreationoleffusionsMedicalmanagementotCLSbeginswithcareluimonitoringof thepatient'slluidandorganperfusionstatus.Thisis achievedby Irequenfdeterminationof bloodpressureandpulse,andbymonitoringorganlunction.whichincludesassessmentol menialstatusandurineoutputHypovolemiais assessedbycalnetenzationandcentralpressuremonitoring

Flexibilitym fluidandpressormanagementis essentiallor maintainingorganperfusionandbloodpressureConsequently,extremecautionshouldbeusedintreatingpatientswithfixedrequirementslorlargevolumesol fluid(eg patientswithhypercalcemia)

PatientswithhypovolemiaaremanagedbyadministeringIVfluids,eithercolloidsorcrystalloidsIVfluidsareusuallygivenwhenthecentralvenouspressure(CVP)isbelow3 lo 4 mmH,0 Correclionol hypovolemiamayrequirelargevolumesol IVfluidsbutcautionis'requiredbecauseunrestrainedfluidadmimslrationmayexacérbaleproblemsassociatedwithedemaformationoreffusions

Withextravascuiarfluidaccumulation,edemaiscommonandsomepatientsmaydevelopascilesor pleuraleffusionsManagementot theseeventsdependson acareluiBalancingol theelfectsof fluidshiltssothatneithertheconsequencesotnypovoiemia(eg impairedorganperfusion)northeconsequencesol fluidaccumulations(eg pulmonaryedema)exceedsthepatient'stolerance

Clinicalexperiencehasshownthaiearlyadministrationot dopamme(1 to 5ug/kg/mm)lo patientsmanifestingcapillaryleaksyndrome,beforetheonsetolhypotension,canhelplo maintainorganperfusionparticularlylo thekidneyandthuspreserveurmeoutputWeightandurineoutputshouldbecarefullymonitorednorganperfusionandbloodpressurearenotsustainedbydopammetherapy,clinicalinvestigatorshaveincreasedthedoseol dopammeto 6 to 10ug/kg/mmor haveaddedphenyiephnnehydrochionde0 to5 ug/kg/mm)to lowdosedopamme(See"CLINICALPHARMACOLOGY"Section"Clinical Experience"SubsectionmPackageInsert)Prolongeduseot pressors.eitherin combinationor asindividualagents,at relativelyhighdoses,maybe associatedwilh cardiacrhythmdistur

bances NOTE: Prior to the use ol any produci mentioned in this para-Õraph, the physician should rater to the package insert for the respec-

ve produci.Failurelo maintainorganperfusion,demonstratedby alleredmentalstatus,

reducedunneoutput,afallinthesystolicblooöpressurebelow90mmHgoronsetofcardiacarrhythmias,shouldleadtoholdingthesubsequentdosesuntilrecoveryotorganperfusionanda returnol systolicbloodpressureabove90 mmHg areObserved(See"DOSAGEANDADMINISTRATION"Section"Dose Modification" SubsectionmPackageInsert)

RecoverytromCLSbeginssoonatlercessationof PROLEUKIN«(aldesleukm)therapyUsually,wilhma fewhours,thebloodpressurerises,organperfusionisrestoredandrésorptionol extravasatedfluidandproteinbeginsIf [herehasbeenexcessiveweightgamoredemaformation,particularlyil associatedwithshortnessofbrealhfrompulmonarycongestion,useofdiuretics,oncebloodpressurefiasnormalized,hasbeenshownlohastenrecovery

Oxygenis givenlo thepatientil pulmonarytunclionmonitoringconfirmslha!P,0-isdecreased

PROLEUKINadmimslrationmaycauseanemiaand/orihrombocylopeniaPackedredbloodcelltransfusionshavebeengivenbothlor reliefofanemiaandto insuremaximaloxygencarryingcapacityPlatelettransfusionshavebeengivento resolveabsoluteIhrombocylopeniaandto reducetheriskofGlbleedingtnaddition,leuko-pemaandneulropemaareobserved

PROLEUKINadministrationresultsm fever,chills,rigors,pruritusandgastrointestinalsideeffectsin mostpatientstreatedat recommendeddosesThesesideellectshavebeenaggressivelymanagedasdescribedm the"CLINICALPHARMACOLOGY"Section."Clinical Experience"Subsectionm PackageInserì

Renalandhepalicfunctionis impairedduringPROLEUKINtreatmentUseolconcomitantmedicationsknownto benephroloxicor hepaloloxicmayfurtherincreasetoxicilytothekidneyorliverInaddition,reducedkidneyandliverfunctionsecondaryio PROLEUKINtreatmentmaydelayeliminationol concomitantmedicationsandincreasetheriskofadverseeventsfromthosedrugs

Patientsmayexperiencementalstatuschangesincludingirritability,contusion,ordepressionwhilereceivingPROLEUKINThesementalstatuschangesmaybeindicatorsol bacleremiaor earlybacterialsepsisMentalstatuschangesduesolelytoPROLEUKINaregenerallyreversiblewhendrugadministrationis discontinuedHowever,alleralionsinmenialstatusmayprogresslorseveraldaysbeforerecoverybegins

Impairmentol thyroidtunctionhasbeenreportedfollowingPROLEUKfNtreatmentA smallnumberol treatedpatientswentonto requirethyroidreplacementtherapyThisimpairmentol thyroidlunctionmaybeamanifestationofaufoimmunily.consequently,extracautionshouldbeexercisedwhentreeingpatientswithknownautoimmunedisease

PROLEUKIN(aldesleukm)enhancementolcellularimmunelunclionmayincreasetheriskofallegratirejectionintransplantpatientsLaboratoryTesisThefollowingclinicalevaluationsarerecommendedtor allpatients,priorlobeginningtreatmentandthendailyduringdrugadministration

•¿�Standardhématologielests-includingCBC,differentialandplateletcounts•¿�Bloodchemistries-includingelectrolytes,renalandhepaticfunctiontesis•¿�Cheslx-rays

All patientsshouldhavebaselinepulmonaryfunctiontesiswitharlena!bloodgasesAdequatepulmonarylunctionshouldtoedocumented(FEy>2litersor275%ol predictedtor heightandage)priorto initialingtherapyAll patientsshouldbescreenedwithastressthalliumstudyNormalelectionfractionandunimpairedwallmotionshouldbedocumentedIf a thalliumstresslestsuggestsminorwallmotionabnormalitiesol questionablesignificance,a stressechocardiogramto documentnormalwallmotionmaybeuseful10excludesignificantcoronaryarterydisease

DailymonitoringduringtherapywithPROLEUKINshouldincludevitalsigns(temperature,pulse,bloodpressureandrespirationrate)andweightIna patientwithadecreasedbloodpressure,especiallylessthan90 mmHg,constantcardiacmom-lormgtorrhythmshouldbeconductedII anabnormalcomplexor rhythmisseen,anECGshouldbeperformedVitalsignsm thesehypoiensivepatientsshouldbelakenhourlyandcentralvenouspressure(CVP)checked

Duringtreatment,pulmonarytunctionshouldbemonitoredonaregularbasisbyclinicalexamination,assessmentol vitalsignsandpulseoximelryPatientswithdyspneaor clinicalsignsol respiratoryimpairment(tachypneaor rates)shouldbefurtherassessedwith arterialbloodgasdeterminationTheselestsare lo berepealedasottenasclinicallyindicated

Cardiacfunctionis assesseddailyby clinicalexaminationandassessmentolvitalsignsPatientswithsignsorsymptomsofchestpain,murmurs,gallops,irregularrhythmorpalpitationsshouldbefurtherassessedwithanECGexaminationandCPKevaluationit thereisevidenceol cardiacischemiaorcongestivehearttatlure,arepealthalliumstudyshouldbedone.

DtuginteractionsPROLEUKINmayailedcentralnervousfunctionTherelore.interactionscouldoccurfollowingconcomitantadministrationof psychotropicdrugs(eg. narcotics,analgesics,antiemelics,sedatives,tranquilizers).

Concurreniadministrationol drugspossessingnephrotoxic(eg ammo-giycosides.mdomethacm),myeiotoxic(eg cytotoxicchemotherapy),cardiotoxic(egdoxorutoicm)or hepalotoxic(eg metholrexate.asparagmase)eltectswithPROLEUKINmayincreaseloudly intheseorgansystemsThesafetyandefficacyofPROLEUKINincombinationwithchemotherapieshasnoibeenestablished

Althoughgiucocorticoidshavebeenshownto reducePROLEUKiN-mducedsideeffectsincludinglever,renalinsufficiency,hyperbilirubmemia.confusionanddyspnea,concomitantadministrationol theseagentswilhPROLEUKINmayreducetheantitumoreffecfivenessofPROLEUKINandthusshouldbeavoided

Bela-biockersandotherantihyperiensivesmaypotentiatethehypotensionseenwithPROLEUKIN(aldesleukm)Caicmogenests.Mulagenesis,Impairmentol FertilityTherehavebeennosludiesconductedassessingthecarcinogenicor mulagenicpotentialol PROLEUKIN(aldesleukm)

Therehavebeennostudiesconductedassessingtheeffectol PROLEUKINonfertility.It is recommendedthatthisdrugnotbeadministeredto fertilepersonsoleithersexnoipracticingetfectivecontraceptionPregnancy.PregnancyCategoryC AnimalreproductionstudieshavenotbeenconductedwithPROLEUKINII isalsonotknownwhetherPROLEUKINcancauseletalharmwhenadministeredtoapregnantwomanorcanatfeclreproductioncapacityInviewol (heknownadverseeffectsol PROLEUKIN.it shouldonlybegiventoapregnantwomanwithextremecaution,weighingthepotentialbeneMwiththe risksassociatedwiththerapyNursingMothersII is noi knownwhetherthisdrugis excretedm humanmilkBecausemanydrugsareexcretedin humanmilkandbecauseof thepotentialforseriousadversereactionsmnursinginfantsfromPROLEUKIN.adecisionshouldbemadewhetherlodiscontinuenursingortodiscontinuethedrug,takingintoaccounttheimportanceolthedrugtothemotherPediatrieUseSafelyandeffectivenessmchildrenunder18yearsol agehavenoibeenestablished

ADVERSE REACTIONSTherateol drugrelateddeathsmthe255metasiaticrenalcellcarcinomapatientsonstudywhoreceivedsingle-agentPROLEUKINwas4%(11/255)

Frequencyandseverityotadversereactionsto PROLEUKINhavegenerallybeenshowntooeOose-relatedandschedule-dependentMostadversereactionsareself-limitingandareusually,butnotinvariably,reversiblewithin2 or3 daysofdiscontinuationol therapy

Examplesol adversereactionswith permanentsequelaeincludemyocardialmlarction.bowelperloralion/mlarctionandgangrene

Themostfrequentlyreportedseriousadversereactionsincludehypotension,renaldysfunctionwithoiiguna/anuna.dyspneaorpulmonarycongestion,andmenialstatuschanges(i e, lethargy,somnolence,contusionandagitation)

Otherseriousloxicilieshaveincludedmyocardialischemia,myocarditis,gangrene,respiratoryfailureleadingto intubation.Glbleedingrequiringsurgery,intestinalperloration/ileus,coma,seizure,sepsisandrenalimpairmentrequiringdialysisTheincidenceol theseeventshasbeenhigherinPS1patientsthaninPS0palients(See"CLINICALPHARMACOLOGY"Section"Clinical Experience"SubsectionmPackageInserì)

Thefollowingdataonadversereactionsarebasedon373patients(255withrenalcellcancerand118withothertumors)treatedwilhtherecommendedeveryBhour15mmuteinfusiondosmgregimenThesepatientshadmefaslalicor recurrentcarcinomaandwereenrolledinmvestigationaitrialsmtheUnitedSlates

Organsystemsm whichreactionsoccurredm a significantnumoerof thepatientstreatedareloundinthefollowingtable

TABLEIIIIncidenceot AdverseEvents

Eventsby EventsbyBodySystem % of Patients BodySystem %otPatientsCardiovascularHypotension(requiring

pressore)SinusTachycardiaA/rhyihmiasAlrialSupraventricularVentricularJunctionalSradycardta

PrematureVentricularContractionsPremature

AlrialContractonsMyocardial

IschemiaMyocardialInfarctionCardiac

ArrestCongestiveHeartFailure

MyocarditisStrokeGangrenePericardiai

EffusionEndocarditisThrombosisGastrointestinalNausea

andVomitingDiarrheaStomatitis

AnorexiaGlBleeding(requiringsurgery)

DyspepsiaConstipationIntestinalPertoralion/lleusPancreatitisNeurologicMenial

StatusChangesDizziness

SensoryDystunclionSpecialSensoryDisorders(vison,

speech,taste)SyncopeMotor

DysfunctionComaSeizure

(¿randmal)Pulmonary

PulmonaryCongestionDyspneaPulmonary

EdemaRespiratoryFailure

(leadingtointubation)fechypnea

PteuralEffusionWheezingApnea

PneumothoraxHemoptysisHepaticElevated

BmrubinElevatedTransaminase

ElevatedAlkalinePhosphatasejaunoiceHepatomegaly85717Qn85317543226776322713

27S27310732

11545210

98

76111645656]lHématologieAnemiaTnrombocylopemaLeukopeniaCoagulation

DisordersLeukocytosisEosinofiliaAbnormal

LaboratoryFindmrjs

HvpomagnesemiaAcidosisHypocalcemiaHypophosphalemiaHypokatemia

HyoefuricemiaHvpoalbuminemiaHypoproleinemia

HyponatrermaHyperkaiemtaAlkalosisHypogiycemiaHypergiycemiaHypccholesleroiemiaHypercalcemia

HypernalremiaHyperphosohatemiaRenai

Otiguria/AnuriaBUNElevation

SerumCrealmmeElevaltonProteinuriaHemaiuriaDysuriaRenal

ImpairmentRequiringDialysisUnnaryRetentionUrinaryFrequencyDermatologie

PruritusErythemaRashDry

SkinE»follaliveDermatitis

Purpura/PetechiaeUrticariaMusculoskelelal

ArthralgiaMyalgia

ArthritisMuscleSpasmEndocrine

HypothyroidismGeneral

Feverand/orChillsPain(allsites)AbdominalL.nest•oFattgue/Weakness/Malaiseinlection(including

urinarytract.injectionsite,catheter

lip.phlebitis,sepsis)Weigh!Gam(>K)%)HeadacheWeight

Loss(>W%)ConjunctivitisInjection

SiteReactionsAllergicReactions(non-anaphylactic)7764341096161615119

987

4442211

117663

6112932i148412614

4266

11•

1895415~532323125431

Otherseriousadverseeventswerederivedfromtrialsinvolvingmorethan1,800patientsHealedwith PROLEUKINbasedregimensusinga varietyol dosesandschedulesTheseeventseachoccurredwithafrequencyof<f%andincludedliveror renalfailureresultingin deathduodena!ulcération,latalintestinalperforationbowelnecrosis,lala!cardiacarresi,myocarditis,andsupraventncuiartachycardia,permanentortransientblindnesssecondarylo opticneuritis,fatalmalignanthyper-Ihermia,pulmonaryedemaresultingm death,respiratoryarrest,fatalrespiratoryfailure,latalstroke,transientischemieattack,meningitis,cerebraledema,pericarditis allergicinterstitialnephritistracheo-esophagealfistulafatalpulmonaryemboli,severedepressionleadingtosuicide

OVERDOSAGESideellectsfollowingine useot PROLEUKIN*(aldesleukm)are dose-related.Administrationol morethantherecommendeddosehasbeenassociatedwithamorerapidonsetol expecteddoselimitingtoxiciliesAdversereactionsgenerallywill reversewhenthedrugis slopped,particularlybecauseits serumhall-liteisshort (See"CLINICALPHARMACOLOGY"Section"Pharmacokinelics"Subsectionin PackageInsert) Any continuingsymptomsshouldbe treatedsupportivelyLilethreateningloxicitieshavebeenamelioratedby theintravenousadministrationotdexamethasonewhichmayresultin lossol therapeuticetfecifromPROLEUKINNOTE:Prior to the use of oexamethasone.(he physicianshouldreferto the packageinserìfor this produci.

ManufacturedbyChironCorporation IEmeryvilleCA94608

issuedMay1992ZO-X-D3

DistributedbyneologyCorporation

Emeryville,CA94608

AACR SPECIAL CONFERENCE IN CANCER RESEARCH

CHEMICALS, MUTATIONS, AND CANCERCo-Sponsored by the National Cancer Institute of Canada

December 7-12, 1992Banff Springs Hotel, Banff, Alberta, Canada

CONFERENCE CHAIRPERSONLawrence A. Loeb / Seattle, WA

SCIENTIFIC PROGRAM

Keynote AddressLawrence A. Loeb / Seattle. WA

Lesion StructureJohn M. Essigmann / Cambridge, MAKenneth Breslauer / Piscataway, NJPaul Hopkins / Seattle, WADinshaw J. Patel / New York. NY

The Biochemistry of MutagenesisG. Peter Beardsley / Cambridge, MADouglas E. Brash / New Haven, CTLeonard C. Erickson / Maywood. ILArthur P. Grollman / Stony Brook, NYB. Singer/ Berkeley, CA

DNA Damage and Mutations byOxygen Free Radicals

Robert A. Floyd / Oklahoma City, OKMax Costa / Tuxedo. NYShosuke Kawanishi / Kyoto. JapanLawrence J. Marnett / Nashville, TNSusumu Nishimura / Taukuba. Japan

Replication and TranscriptionPhilip C. Hanawalt / Stanford. CAHarrison Echols / Berkeley. CAMyron F. Goodman / Los Angeles, CAThomas A. Kunkel ' Research Triangle Park. NC

Daniel Reines / Atlanta. GA

DNA Repair DiseasesVeronica M. Mäher/ East Lansing. MlR. Stephen Lloyd / Nashville, TNRoger A. Schultz / Baltimore, MDChristine A. Weber / Livermore, CAMalcolm C. Paterson / Edmonton, Canada

Endogenous MutagenesisLeona D. Samson / Boston. MAMark Meuth / Salt Lake City, UTJeffrey H. Miller / Los Angeles. CARoeland M. Schaaper / Research Triangle Park, NCMutsuo Sekiguchi / Fukuoka, Japan

Genomic InstabilityThea D. Tlsty / Chapel Hill. NCFrederick W. Alt / New York, NYCurtis C. Harris / Bethesda, MDBernard S. Strauss / Chicago, ILTed Weinert / Tucson, AZ

Genetic HomeostasisRobert H. Haynes Toronto, CanadaBruce Demple / Boston, MACarol A. Gross / Madison. WlPeter Herrlich / Karlsruhe, GermanyMiroslav Radman Paris. France

Information and Application Forms

American Association for Cancer ResearchPublic Ledger Building620 Chestnut Street, Suite 816Philadelphia, PA 19106-3483

(215) 440-9300 (215) 440-9313 (FAX)

Application Deadline: October 26, 1992

The Division ofCancer Etiology

National Cancer InstituteAnnounces To the Scientific Community The Availability of the FollowingResources/Services For Cancer Related Research As Noted Below:

Biological Resources

•¿�Cell Culture Identification Service. UsingIsozyme Analysis, Immunofluorescence andKaryotypic Analysis (Chromosome Banding)

Contact: Dr Ward PetersonChildren's Hospital of Michigan

3901 Beaubien BoulevardDetroit, Ml 48201(313)745-5570

Citing Contract #N01-CP-85645

Cost: Inquire

•¿�Goat Antisera Against: Avian, Bovine, Feline,Murine, and Primate Intact Viruses and ViralProteins; Antibodies to Immunoglobulins for anumber of species. Preimmune Sera availablefor some Virus Antisera.

Contact: Alice K. Robison, Ph.D.BCB RepositoryQuality Biotech, Inc.1667 Davis StreetCamden. NJ 08104(609) 966-8000(609) 342-8078 FAX

Citing Contract #N01-CP-15665

Cost: $75.00/5 ml (Antisera)25.00/5 ml. (Preimmune Sera)65 00/100 ml. (Immunoglobulins)(Frozen Material)

•¿�Viruses: Avian, Feline, Murine, and PrimateViruses Produced in vivo and in vitro.

Contact: Alice K Robison, Ph.D.BCB RepositoryQuality Biotech, Inc.1667 Davis StreetCamden. NJ08104(609) 966-8000(609) 342-8078 FAX

Citing Contract «M01-CP-15665

Cost: Inquire

•¿�Monoclonal Antibodies are available withspecificities for synthetic peptides representingthe ammo acid sequences of the left end. rightend and active site of the oncogene products ofavian and mammalian retroviruses. Blockingpeptides are also available, as are a limitednumber of cell lines producing the monoclonalantibodies.

Contact: Alice K Robison, Ph.D.BCB RepositoryQuality Biotech, Inc.1667 Davis StreetCamden. NJ 08104(609) 966-8000(609) 342-8078 FAX

Citing Contract #N01-CP-15665

Cost: Peptides —¿�$2500/mgAscites Fluid —¿�45.00/ml.Cell Culture —¿�100.00/culture.

(Plus Shipping and Handling)

•¿�Human sera from donors with variousmalignancies (including nasopharyngealcarcinoma), non-malignant disorders,and from normal individuals.

Contact: Program Director, ResearchResources. BiologicalCarcinogenesis Branch,

DCE. NCI. NIHExecutive Plaza North, Room 540Bethesda. MD 20892(301)496-1951(301) 496-2025 FAX

Cost: Shipping and handling charges only

•¿�The Division of Cancer Etiology's Registry of

Experimental Cancers announces the availability of 16 different study sets containing histologieslides of rodent tumors. The study sets, withaccompanying syllabi, illustrate a variety ofspontaneous and induced tumors, chiefly ofrats, mice, and mastomys. Each set is availableto cancer investigators worldwide, withoutcharge, for up to two months Requests orinquiries should be addressed to:

Contact: Registry of Experimental CancersNational Cancer InstituteBuilding 41 Room D311NIH. Bethesda. MD 20892USA

Chemical Resources

•¿�Analytical support for the collection,separation, and elucidation of environmentalcarcinogens including combustion and smoking-related exposures. A contractor with experiencein the development of analytical methods for thedetermination of constituents of cigarette smokeand cigarette smoke condensâtes, and of specialty instrumentation for inhalation toxicology isavailable to assist qualified investigators withparticular interest in human and animal modelexposure to environmental and sidestreamsmoke An extensive chemical data base onsmoke and smoke condensatecomponents is available

Contact: Harold E Seifried. Ph.D.Chemical and Physical

Carcinogenesis Branch. DCE. NCIExecutive Plaza North, Room 700Bethesda. MD 20892(301)496-5471(3011496-1040 FAX

Cost: Inquire

•¿�Chemical Carcinogen Reference StandardRepository Reference quantities of over 750compounds are available The newest additionsare dilute aqueous standards of PAHdeoxyguanosme-3'-monophosphates forRanderath "P post labelling assays Otherclasses of available compounds are feca-pentaenes, food mutagens, polynucleararomatic hydrocarbons (PAH). PAH metabolites,radiolabeled PAH metabolites, nitrogen hetero-cycles. nitrosamines/nitrosamides, aromaticamines, aromatic amine metabolites, azo/azoxyaromatics, inorganics, nitroaromatics. pesticides, Pharmaceuticals, natural products, dyes,dioxins and chlorinated aliphatics A number otradiolabeled PAH metabolites and nitrosaminesare also available Data Sheets provided withthe compounds include chemical and physicalproperties, analytical data, hazards, storage,and handling information. Catalog availableupon request.

Contact: Manager. NCI ChemicalCarcinogen Repository

Midwest Research Institute425 Volker BoulevardKansas City. MO 64110(816)753-7600, Ext. 523(816)753-3664 FAX

Manager, NCI RadiolabeledChemical Repository

CHEMSYN Science Laboratories13605 W. 96th TerraceLexena. KS66215(913)541-0525(913) 888-3582 FAX

Cost: Subiect to chemical class code andquantity (see catalog) includes handling and shipping charges

Epidemiology Resources

•¿�The Tumor Virus Epidemiology Repository(TVER) contains sera and other biological samples from more than 13,000 patients and controls obtained in 12 different countries. TheTVER was established primarily to support collaborative research on the role of Epstein-Barrvirus (EBV) in Burkitt's lymphoma, nasopharyn-

geal carcinoma, and related diseases

The TVER is able to adjust its collection to facilitate the development of new collaborative studies In addition, some samples are available forreagents and independent research. The mostextensive collections are serum samples frompatients with Burkitt's lymphoma (sera from

more than 1,000 patients).

Contact: Dr Paul H LevineEnvironmental Epidemiology

Branch. DCE, NCI, NIHExecutive Plaza North. Room 434Bethesda, MD 20892(301)496-8115

Cost: Free to Collaborating Investigators;Others: Dependent on Processing

Time

•¿�The National Institute of Allergy and InfectiousDiseases and the National Cancer Institute havedeveloped a repository of biological specimensfrom homosexual men. The specimens werecollected through contracts with five maior US.universities for studies of the natural history ofacquired immune deficiency syndrome (AIDS).

Information about applying for collaborative useof these specimens is available from the NIAIDProiect Officer or the NCI Co-Pro|ect Officer.

Contact: Chief, Epidemiology Branch, AIDSProgram

National Institute of Allergy andInfectious Diseases

CDC Bldg . Room 240National Institutes of HealthBethesda. MD 20892

or to ChiefExtramural Programs Branch, EBP,Division of Cancer Etiology, NCIExecutive Plaza North, Room 535Bethesda, MD 20892

•¿�Human fibroblast cultures from individuals athigh risk of cancer, members of cancer-pronefamilies, and normal family members are available Collection is historical with unknown viability and contamination status Catalogue unavailable Information requests should includepotential use of cultures.

Contact: Chief, Family Studies Section. EEB,DCE. NCI, NIH

Executive Plaza North, Room 439Bethesda, MD 20892(301)496-4375

Cost: Free to collaborating investigators.Others: $70/cell line.

•¿�The National Cancer Institute has availablethe Animal Morbidity/Mortality Survey ofColleges of Veterinary Medicine in NorthAmerica (also known as the Veterinary MedicalData Program). This unique registry of veterinarymedical information represents patient data onanimals seen at collaborating veterinary teaching facilities; 3 million hospital episodes havebeen abstracted and computerized in a standardized record format. Disease information iscoded using the scheme of the StandardNomenclature of Veterinary Disease andOperations The computer tapes will be madeavailable upon request.

Contact: Dr. Howard M HayesEnvironmental Epidemiology BranchEpidemiology and Biostatistics

ProgramDivision of Cancer EtiologyExecutive Plaza North, Room 443Bethesda. MD 20892(301)496-1691

Cost: Inquire

•¿�The Epidemiology and Biostatistics Programof the National Cancer Institute has developedthe Observed versus Expected (0/E) softwaresystem which calculates: ( 1) the number ofobserved events (e.g cancer cases or deaths)in a study group at risk; (2) the number ofexpected events in a study group based on therate of occurrence in some standard or referentpopulation; (3) the ratio of observed to expectedevents; and (4) the significance of this ratio Thesystem is user friendly and capable of executinga series of calculations by different variablessuch as age. time group, date of exposure, ageat date of exposure, duration of exposure, yearrelative to entry and cause of event. The 0/ESystem provides tables by race, sex and userdefined variables, allows user defined latencyintervals and accepts standard or user prepared rates 0/E is written in COBOL and isexportable to most mainframes.

Contact: Ruth WolfsonEpidemiology and Biostatistics

ProgramDivision of Cancer Etiology. NCIExecutive Plaza North, Room 531Bethesda. MD 20892(301)496-1606

Cost: Free to investigators interested in epidemiologie research.

Environmental Cancer•¿�NCI's Chemical Carcinogenesis Research

Information System (CCRIS) is available onlinethrough the National Library of Medicine's

Toxicology Data Network (TOXNET) system.Through an interagency agreement betweenNCI and NLM, the CCRIS database has beenbuilt and will be maintained and updated as oneof TOXNET's sponsored databases in the broad

areas of chemistry, toxicology, and hazardouswaste information The CCRIS database contains evaluated data and information on carcinogens, mutagens. tumor promotors. cocarcmo-gens, metabolites of carcinogens, andcarcinogen inhibitors derived from publishedreview articles, ongoing current awareness survey of primary literature, NCI/NTP's short- andlong-term bioassay studies, the IARCMonographs on the Evaluation of CarcinogenicRisk or Chemicals to Man, and special studiesand reports.

Contact: Dr. Thomas P. CameronOffice of the DirectorDivision of Cancer EtiologyNational Cancer InstituteExecutive Plaza North, Room 712Bethesda, MD 20892(301)496-1625

Cost: Inquire

•¿�The Special Assistant for EnvironmentalCancer, Office of the Director, announces theavailability of a limited number of copies of thefollowing publications, which have been prepared under contract to NCI:

Survey of Compounds Which Have Been Testedfor Carcinogenic Activity, PHS-149. 1987-1988and 1989-1990

Contact: Dr. Thomas P. CameronOffice of the DirectorDivision of Cancer EtiologyNational Cancer InstituteExecutive Plaza North. Room 712Bethesda, MD 20892(301)496-1625

Cost: Inquire

•¿�TheNational Cancer Institute, along withthe National Institute of Environmental HealthSciences, the Centers for Disease Control, andthe Food and Drug Administration, has, formany years, supported a study by the MichiganDepartment of Public Health dealing with anaccidental exposure to polybrominatedbiphenyls.

The Michigan Long Term PBB Study is a well-maintained longitudinal database on 4.000participants from rural farms in Michigan.This group was exposed to polybrominatedbiphenyls through consumption of contaminatedfarm animals and food products. The cohort wasenrolled and characterized in 1975-76, establishing a database containing demographic,health history, medical condition, reproductivehistory, blood and tissue analyses, and chemical/environmental exposure information. Majorlife events—birth, death, cancer and mapr illnesses have been confirmed and updatedannually. The project is currently completing adetailed recharacterization of all cohort membersand their children. This longitudinal database isavailable for collaborative research investigatingbiological and human health outcomes fromhalogenated biphenyl exposure.

Contact: Dr. Harold E B HumphreyMichigan Department of

Public HealthDivision of Health Risk Assessment3423 North Logan, P.O. Box 30195Lansing, Ml 48909(517)335-8350

Cost: Free to qualified investigators

AMERICAN ASSOCIATION FOR CANCER RESEARCHSCIENTIFIC CONFERENCES: 1992-1994

DECEMBER 7-12, 1992Chemicals, Mutations, and Cancer

Co-Sponsored by the NationalCancer Institute of Canada

Chairperson: Lawrence A. Loeb. Seattle, WABanff Springs Hotel, Banff. Alberta, Canada

FEBRUARY 1-6, 1993Oncogenes and Antioncogenes in Cell

Differentiation, Development, andHuman Cancer

Chairperson: Carlo M. Croce, Philadelphia, PABig Sky Resort, Big Sky, MT

MARCH 15-20, 1993Mechanism of Action of Retinoids,Vitamin D, and Steroid Hormones

Chairpersons: Michael B. Sporn, Bethesda, MD;Ronald M. Evans, San Diego, CA; DavidMangelsdorf. San Diego. CA

Banff Centre, Banff. Alberta, Canada

APRIL 13-17, 1993Model Systems in Cancer Research

(Tentative Title)Supported by a Generous Grantfrom the General Motors Cancer

Research FoundationChairpersons: Leland H. Hartwell, Seattle, WA:

Peter K. Vogt, Los Angeles, CA; George F.Vande Woude. Frederick, MD

San Luis Hotel, Galveston, TX

MAY 19-22, 199384th Annual Meeting

Chairperson: Michael B. Sporn, Bethesda, MDOrange County Convention Center, Orlando, FL

NOVEMBER 7-11, 1993Tumor Immunology: Basic and

Clinical AspectsChairperson: Ralph A. Reisfeld, San Diego, CAGrove Park Inn, Asheville, NC

NOVEMBER 16-19, 1993Importance of Genetic Susceptibility in

Environmental CarcinogenesisJoint Meeting with International Association

for Research on CancerChairpersons: Frederick P. Li, Boston, MA, and

Ruggero Montesano, Lyon, FranceIARC, Lyon, France

DECEMBER 5-9, 1993Signal Transduction in Cancer TherapyJoint Meeting with British Association for

Cancer Research and EuropeanOrganisation for Research and Treatment of

Cancer (RAM Group)Chairperson: Garth Powis, Tucson, AZSan Juan Hotel, San Juan, PR

JANUARY 17-22, 1994Risk Assessment in Environmental

CarcinogenesisChairpersons: Philip C. Hanawalt, Berkeley, CA;

James A. Swenberg, Chapel Hill, NCWhistler Resort and Conference Center, Whistler,

B.C., Canada

JANUARY 31-FEBRUARY 5, 1994Molecular Genetics of Progression

and MetastasisChairperson: Lance A. Liotta, Bethesda, MDBig Sky Resort, Big Sky, MT

AACR members will receive brochures on theabove special conferences as soon as they areavailable. Nonmembers should call or write:

American Association for Cancer ResearchPublic Ledger Building620 Chestnut Street, Suite 816Philadelphia, PA 19106-3483215-440-9300 •¿�215-440-9313 (FAX)

AACR SPECIAL CONFERENCE INCANCER RESEARCH

MECHANISM OF ACTION OF RETINOIDS,VITAMIN D, AND STEROID HORMONES

March 15-20, 1993A Banff Qentr6j ßanff;Alberta, Canada

CONFERENCE CHAIRPERSONSMichael B. Sporn / Bethesda, MDRonald M. Evans / San Diego, CA

David Mangelsdorf / San Diego, CA

SCIENTIFIC PROGRAM

Keynote AddressRobert G. Boeder / New York, NY

DNA Binding HeterodimersKazuhiko Umesono San Diego. CAJeffrey D. Milbrandt / St. Louis, MOLeonard P. Freedman / New York, NYChristopher K. Glass / San Diego, CAMagnus Pfahl / San Diego. CA

3-Dimensional Structure of Receptorsand Binding ProteinsPaul B. Sigler ' New Haven. CT

Marcia Newcomer I Nashville, TNPeter Wright / San Diego, CA

Development and DifferentiationDavid Mangelsdorf / San Diego. CAGregor Eichele Houston. TXAnita B. Roberts / Bethesda. MD

Genetic Regulation by Retinoids andSteroidsLorraine J. Gudas / New York, NYVincent Giguere / Toronto, Canada

Vitamin DJ. Wesley Pike / San Diego. CALise Binderup ' Copenhagen, Denmark

Steven L. Teitelbaum / St. Louis. MOStavros Manolagas / Indianapolis. IN

Studies of Disease and TherapyAnne DeJean / Paris. FranceBjörnVennstrom / Stockholm. SwedenBenjamin G. Neel / Boston, MA

Steroids and Related ReceptorsBert W. O'Malley / Houston, TX

Stephen Green / Macclesfield, EnglandRoger L. Miesfeld / Tucson, Arizona

Metabolism of RetinoidsJoseph F. Grippo / Nutley, NJRobert R. Rando / Boston, MARichard Heyman / San Diego. CA

Information and Application Forms

American Association for Cancer ResearchPublic Ledger Building620 Chestnut Street, Suite 816Philadelphia, PA 19106-3483

(215)440-9300 (215) 440-9313 (FAX)

AACR SPECIAL CONFERENCE IN CANCER RESEARCH

OncogenesandAntioncogenesinDifferentiation,Development,andHumanCancer

February1-6,1993BigSkyResort,BigSky,Montana

CONFERENCE CHAIRPERSON

Carlo M. Croce / Philadelphia,PA

PROGRAM COMMITTEE

Stuart A. Aaronson / Bethesda, MDMario R. Capecchi / Salt Lake City, UT

Douglas Hanahan / San Francisco,CA

SCIENTIFIC PROGRAM

KeynoteAddressRaymondL. White/ SaltLakeCity,UT

GeneKnockoutsbyHomologousRecombinationIMarioR.Capecchi/ SaltLakeCity,UTAllanBradley/ Houston,TXTylerJacks/ Cambridge,MABruceM.Speigelman/ Boston.MA

GeneKnockoutsbyHomologousRecombinationIIErwinWagner/ Vienna,AustriaHaroldE. Varmus/ San Francisco,CADouglasHanahan/ SanFrancisco.CA

SignalTransductionandCancerIStuartA.Aaronson/ Bethesda,MDLewisC.Cantley/ Boston,MAJohnJ. Cohen/ Denver,CODavidV.Goeddel/ S.SanFrancisco,CA

SignalTransductionandCancerIIMichaelH.Wigler/ ColdSpringHarbor.NYEdwardB.Ziff/ NewYork.NYMichaelJ.Weber/Richmond.VA

ChromosomalTranslocationsandCancerCarlo M. Croce/ Philadelphia,PAMichaelL. Cleary/ Stanford,CAEli Canaani Philadelphia,PAAnne Dejean/ Paris.France

Tumor Suppressor GenesEricJ. Stanbridge/ Irvine,CAWen-HuaLee/ SanAntonio,TXDavidE.Housman/ Cambridge,MALennartPhilipson/ Heidelberg,GermanyKarenVousden/ London,England

ExpressionofActivatedOncogenesinTransgenicMiceI andIIRobertS. Coffey/Nashville,TNGilbertJay/Rockville,MDGeorgeF. VandeWoudeFrederics.MDAllan BalmainGlasgowScotlandAdditionalSpeakerstobeAnnounced

InformationandApplicationForms

American Association for Cancer ResearchPublic Ledger Building620 Chestnut Street, Suite 816Philadelphia, PA 19106-3483

ApplicationDeadline:December7, 1992 215-440-9300 215-440-9313 (FAX)

COVER LEGEND

^ ConÅ“rResearchf 1 nnrn ni-Tn iirmr n inni roírnn 11«•¿�!¡«MBHn

«u............

Serious cutbacks in federal support of extramural cancerresearch have limited the ability of the National CancerInstitute to contribute at its traditional level. This fact hasled to a greatly expanded role for private funding agencies.One of these, the Cancer Research Fund of the DamonRunyon-Walter Winchell Foundation, has achieved a uniqueimpact, despite its small budget, in support of high caliberinvestigators and research programs. Recognizing that thelimited funds at its disposal should be narrowly targeted tospecific areas of greatest need and benefit, the Fund followsa policy of supporting highly promising young investigatorswho are starting clinical careers in cancer research under thementorship of outstanding senior scientists. Such a policyserves the double purpose of contributing new knowledgeand of training a new generation of researchers under optimal conditions to advance developments. Over the 44 yearsof its existence, the Fund has disbursed more than $76million. The degree of its success can be measured by itsstellar record of having supported 37 investigators (as eitherfellows or sponsors) who have attained the supreme distinction of the Nobel Prize. Sidney Altman, a fellow in 1967-1969, won the Nobel award in chemistry in 1989, andSusumu Tonegawa, a fellow in 1969-1970, was the Nobelawardee for medicine in 1987. Three sponsors of DamonRunyon fellows were Nobel laureates in 1989: J. MichaelBishop and Harold E. Varmus in medicine; and Thomas J.Cech in chemistry. A large number of their former fellowsare prominent figures in today's cancer research.

A high standard of excellence in the choice of fellows isfostered by an experienced and accomplished broad-based

Scientific Advisory Committee of 20 members, under a 17-member Board of Directors, seven of whom are leaders incancer research. President of the Fund is Richard J. O'Reilly,

Chairman, Department of Pediatrics, Memorial Sloan-Ket-tering Cancer Center. Two types of fellowships are awarded.Level 1 fellowships are for new M.D.s or Ph.D.s, or theequivalent, who receive an initial annual stipend of $23,000,which can be renewed for 2 years with increased stipends of$28,000 and $30,500. Level 2 fellowships are for physicianscientists who have completed up to three years of residencyor clinical fellowship. Their annual stipends start at $42,000.Fellows are United States citizens who work in United Statesinstitutions, but under certain circumstances a United Statesfellow may work abroad or a foreign fellow may work in theUnited States. Approximately $4 million are expended annually in support of approximately 125 fellows.

Few of the younger generation remember either DamonRunyon or Walter Winchell, but both were extremely popular before and during World War II. Damon Runyon wasa newspaper columnist covering the Broadway beat and wasan engaging writer of stories of the colorful characters making up the fringes of the New York theatre and horse racecrowd of that time. Many of his stories have become legendary movies and plays, and the musical "Guys and Dolls" is

based on Damon Runyon characters of the early Broadwayscene. Walter Winchell was a newspaper and radio commentator, whose popularity made him a household word. Healso specialized in the Broadway theatre scene. When Damon Runyon died of throat cancer in 1946, Walter Winchell,a close friend, used his immense popularity among the publicand theater world to crusade for funds to fight the dreadeddisease in Damon Runyon's memory. When Walter Win

chell died in 1971, the Fund adopted the name DamonRunyon-Walter Winchell Cancer Research Fund, an appropriate testimonial to Winchell's dedication to its continued

support.The Fund receives its support from legacies, foundations,

individual and corporate contributions, and investment income. In addition, it has an unusual income source fromBroadway theaters. A number of tickets are set aside foreach performance, which the Fund sells at the box-officeprice plus a tax-exempt contribution. Approximately$400,000 are derived each year from this source. ExecutiveDirector Rebecca Kry notes that the current Board of Directors is playing an integral part in fostering the financialstability of the Fund.

Pictured on the cover are: bottom, Damon Runyon (left):,Walter Winchell (right); top, Richard J. O'Reilly, President

(left); Cleon T. Knapp, Chairman of the Board (right); andRebecca R. Kry, Executive Director (center), to whom weare indebted for the photographs and information.

Sidney Weinhouse