UnitTwentyFiveADENOIDCYSTICCARCINOMAOFTHESA;IVARYGLANDSustainedCompleteResponsetoChemotherapy.G.THOMASBUDD.MD.AND.C.W.GROPPE.MDApatientdevelopedwidelymetastaticadenoidcysticcarcinomaoftheparotidelandafterseverallocalrecurrences.Acompleteregressionofpleural,pulmonaryparenchymal,cutaneous,andbonemetastaseswasseenfollowingtherapywith5-fluorouracil,Adriamycin,andmitomycinC.Thisisthesecondcompleteresponsetochemotherapyreportedforapatientwithmetastaticadenoidcysticcarcinomaofsalivaryglandorigin.BothcompleteresponsesandseveralpartialresponseshavefollowedtreatmentwithAdriamycin,suggestingthatthisdrugisactiveinthedisease.Cancer51:589-590,1983ADENOIDCYSTICCARCINOMAhasbeenanuncommon,slowgrowingtumorcharacterizedbymultiplerecurrences.Althoughthishistologicentityisoccasionallyrepresentedintumorsoftheskin,breastandcervix,aswellastumorsarisingfromlacrimalglandsandtheceruminousglandsoftheexternalauditorycanal,adenoidcysticcarcinomamostfrequentlyoriginatesinamajororminorsalivarygland.Thistumorwasfoundin10%ofpatientspresentingwithsalivaryneoplasmstoMemorialSloan-KetteringCancerCenterandin25%ofpatientspresentingtoM.D.AndersonHospitalwithneoplasmsofthemajorsalivaryglands(parotid,submaxillary,andsublingual),accountingfor5.2%ofallheadandneckcancers.Biologically,adenoidcysticcarcinomaischaracterizedbyslowgrowthwithinsidiousinvolvementoflocalstructures.Perineuralinvasionistypicalwhenthetumorislocatedinproximitytonervoustissue,andinfiltrativegrowthistherule.Clinically,thesecharacteristicsaremanifestasatendencyforlocalrecurrenceinapproximatelytwothirdsofpatients.Althoughdirectextensioncaninvolvelymphnodes,lymphaticspreadtoregionalnodesisnotcommon,occurringinonly15%ofthepatients.Distantmetastasesontheotherhand,occurin42-58%ofthepatients.Thelungsarefavoredsitesformetastases,althoughbone,liver,centralnervoussystem,andotherorgansmaybecomeinvolved.Whilerelativelylongsurvivalcanoccurinthefaceofmetastaticdisease,effectivesystemictherapywouldbedesirableinviewofthetendencyforpatientswithadenoidcysticcarcinomatodevelopdistantmetastases.Theauthorsreportacompleteremissionfollowingtreatmentwith5-fluorouracil.Adriamycin(doxorubicin),andmitomycinC,inapatientwithwidelymetastaticadenoidcysticcarcinomaoftheparotidgland.CaseReportInOctober1980,a29-year-oldwhitewomanwasreferredtotheClevelandClinicformetastaticadenoidcysticcarcinomaoriginatingintheleftparotidgland.ThepatienthadundergoneresectionofaleftparotidtumorinSeptember1967foranadenoidcysticcarcinomashowinghistologicevidenceofearlyperineuralinvasion.AlocalrecurrenceinJanuary1972wastreatedbysurgicalresection.SubsequentlocalrecurrencesweretreatedbysubtotalparotidectomyinJanuary1976,andexcisioninJanuary1977,witharesectionofrecurrenttumorandaninvolvednodeinJanuary1978necessitatingsacrificeoftheleftfacialnerve.AlocalrecurrenceinOctober1978wastreatedwith3000radofmegavoltageradiationdeliveredbylinearacceleratoraswellas2000radoforthovoltageradiation.ThepatientfirstnotedchestpaininJuly1980,whichwasfollowedbythedevelopmentofdyspneaonexertionandadrycoughinSeptember1980.Aright-sidedpleuraleffusionwasnotedandadecubituschestx-rayrevealedtwonodulardensitiesintherightmid-lungfields.Thoracentesiswasperformedandthefluidwasfoundtocontainmalignantcellscytologicallyconsistentwithmetastaticadenoidcysticcarcinoma.Abonescanshowedincreaseduptakeoverthepubis.L1,T5andtherightribs;aliverspleenscanwasnormal.Serumchemistriesrevealedanelevationofthealkalinephosphataseto339U/L.Abiopsyspecimenofacutaneousnodulelocatedonthepatient’sabdomenrevealedmetastaticcarcinoma.OnOctober17,1980,thepatientreceivedherfirstcourseofcombinationchemotherapywithFAM.Treatmentwaswith5-fluorouracil500mg/m2andAdriamycin30mg/m2intravenouslyeveryfourweeks.MitomycinCwasgivenonthefirstdayandeveryeightweeksatadosageof10mg/m2.ByFebruary26,1981,examinationofthepatient'schestx-rayshowedimprovementandtheserumalkalinephosphatasehadfallento118U/L.AbonescanperformedJune25,1981wasnormal.OnJuly2,1981,thepatient'schestXJraywasclearherserumalkalinephosphatasewasnormalat52U/L,andphysicalexaminationrevealednoevidenceofdisease.SheremainedincompleteremissionwhenseenonOctober30,1981.WhilestillreceivingtherapywithFAM,thepatientleadsaphysicallyactivelifeandremainsdiseasefreeafter12monthsoftreatment.DiscussionThisisthesecondreportedcaseofacompleteremissionofmetastaticadenoidcysticcarcinomaofthesalivaryglandinducedbychemotherapy.Theotherreportedcompleteresponseoccurredfollowingtherapywithvincristine,intravenouscyclophosphamide,andAdriamycin.inthatcase,disease13rogressionhadoccurredduringtreatmentwithvincristineandoralcyclophosphamide,suggestingthatAdriamycinwastheagentresponsiblefortheinductionofremission.PartialresponseshavebeenreportedfollowingtherapywithAdriamycinandtherelatedanthracyclinedaunomycin.OffivepatientswithadvancedcarcinomaoftheparotidglandtreatedwithAdtiamycin,cisplatinandcyclophosphamide,twocompleteandthreepartialresponseswerereported,althoughnoneofthesepatienttumorsdemonstratedadenoidcystichistology.Asinglepartialresponsetohexamethylmelaminetherapyhasbeenreported,althoughclassicalalkylatingagentshavenotbeeneffective.5-Fluorouracilhasbeenshowntohavesomeactivityagainstadenoidcysticcarcinomawhengiveneigberintra-arteriallyorintravenously.Althoughthedifficultiesinherentintheretrospectiveassessmentofthebenefitsoftherapyinthisuncommonandslowgrowingtumorsystemhavebeenpointedout,objectiveresponsescanbedocumented.Inourpatient,aclear-cutimprovementinperformancestatusandlifestylehasaccompaniedamarkedimprovementinobjectivemeasuresofdisease,andaprolongationofsurvivalmightbepresumed.Adriamycinwouldseemtobethemosteffectiveagentforthetreatmentofmetastaticadenoidcysticcarcinomaofthesalivaryglands,although5-fluorouracilhasalsoshownsomeacti