Actinomycin D for Methotrexate-failed Lowrisk Gestational Trophoblastic Neoplasia

283OBJECTIVE: To determine outcomes and factors associ-ated with failure of 5-day actinomycin D for treatment ofmethotrexate-failedlow-riskgestationaltrophoblasticneoplasia (GTN).STUDYDESIGN:Were-viewed the records of 358 pa-tientstreatedwithmetho-trexate0.4mg/kg(max25mg) IV push q.d. 5 d every14dforFIGO-defined,low-risk GTN between 1979 and2009. Actinomycin D 0.5 mgIV push q.d. 5 d every 14 dwas given to 64 of 68 patients (18%) who failed metho-trexate: 48 (75%) for resistance and 16 (25%) for toxici-ty. Adjuvant surgery was used in selected patients. Clin-icalresponseandsurvivalaswellasfactorsaffectingoutcomes were analyzed retrospectively.RESULTS:Thecompleteresponseratetosecondarychemotherapy with actinomycin D for failed methotrex-ate treatment of low-risk GTN was 75% (48/64), includ-ing71%(34/48)formethotrexateresistanceand88%(14/16)formethotrexatetoxicity.All20patients(6%)whofailedsequentialsingle-agentchemotherapywithmethotrexateandactinomycinDwereplacedintoper-manent remission with the use of multiagent chemother-apy with or without surgery. The only factor significant-ly associated with resistance to secondary actinomycin Dchemotherapy was clinicopathologic diagnosis of chorio-carcinoma versus postmolar GTN (56% versus 20%, p=0.025).CONCLUSION:Actinomy-cinD0.5mgIVq.d. 5devery14dusedassecond-ary therapy in methotrexate-failed low-risk GTN resultedina75%completeresponserate and eventual 100% curewithsubsequentmultiagentchemotherapywithorwith-outsurgery.Resistancetosequentialmethotrexateandactinomycin D chemotherapy was significantly associat-ed with original FIGO score 3 and clinicopathologic di-agnosisofchoriocarcinoma.(JReprodMed2012;57:283287)Keywords:actinomycinD,chemotherapy,gesta-tional trophoblastic neoplasia, methotrexate.Patients categorized as having low-risk gestationaltrophoblastic neoplasia (GTN) usually can be treat-edsuccessfullywithsingle-agentmethotrexateoractinomycinDchemotherapy.1Severaldifferentoutpatient chemotherapy protocols have been usedFrom the John I. Brewer Trophoblastic Disease Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois.Presented at the XVIth World Congress on Gestational Trophoblastic Diseases, Budapest, Hungary, October 1619, 2011.Address correspondence to: John R. Lurain, M.D., 250 East Superior Street, Suite 05-2168, Chicago, IL 60611 (jlurain@nmff.org).Financial Disclosure: The authors have no connection to any companies or products mentioned in this article.Actinomycin D for Methotrexate-Failed Low-Risk Gestational Trophoblastic NeoplasiaJohn R. Lurain, M.D., Eloise Chapman-Davis, M.D., Anna V. Hoekstra, M.D., M.P.H.,and Julian C. Schink, M.D.The Journal of Reproductive Medicine0024-7758/12/5707-80283/$18.00/0 Journal of Reproductive Medicine, Inc.The Journal of Reproductive MedicineThe complete response rate tosecondary actinomycin Dchemotherapy for failedmethotrexate treatment of low-risk GTN was 75%...which,inmostlynonrandomized,retrospectivestudies,haveyieldedoverallprimaryremissionrates ranging from 4994%.2,3In general, the week-lyintramuscularorintermittentintravenousinfu-sion methotrexate and the biweekly single-dose ac-tinomycin D protocols are less effective than one ofthe 5-day methotrexate or actinomycin D protocolsandthe8-daymethotrexate-folinicacidregimen.Also, older patient age, higher human chorionic go-nadotropin (hCG) level, nonmolar antecedent preg-nancy,histopathologicdiagnosisofchoriocarcino-ma,presenceofmetastaticdisease,andhigherFIGOscorehaveeachbeenassociatedwithanin-creased risk of initial chemotherapy resistance.1,4Therefore,appropriateselectionofsecondarychemotherapywiththealternatesingle-agentver-susmultiagentchemotherapyisimportanttopro-videforoptimalresultswiththeleasttoxicity.Chemotherapy is usually changed to an alternativesingle agent if the hCG level plateaus above normalafter an initial good response or if toxicity precludesan adequate dose or frequency of the initial chemo-therapeuticagent.If,ontheotherhand,thereisasignificant elevation in hCG level, development ofmetastasesorresistancetosequentialsingle-agentchemotherapy,multiagentchemotherapyshouldbe initiated.Severalstudieshavereportedontheeffective-ness of actinomycin D as a second-line single agentafterfailureofmethotrexateastheinitialchemo-therapyforlow-riskGTN.5-11Weundertooktoevaluate the results of 5-day actinomycin D (0.5 mgIVq.d. 5devery14d)assecondarytherapyforpatients with low-risk GTN who failed initial 5-daymethotrexate(0.4mg/kgmax25mgIVq.d. 5devery 14 d) because of resistance or toxicity and todeterminefactorsresponsibleforactinomycinDfailureandeventualneedformultiagentchemo-therapy.Materials and MethodsThreehundredfifty-eightpatientswithFIGO-defined low-risk GTN (stages IIII, score