concepts in use of high dose methotrexate therapy外语英文电子书

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1、ClinicalChemistry42:8(B)1322-1329(1996)Conceptsinuseofhigh-dosemethotrexatetherapySTEVENP.TREONandBRUCEA.CHABNER*Incancerchemotherapy,routinemonitoringofdrugcon-mas,andcertainadultnon-Hodgkinlymphomas,particularlycentrationshasbeenpracticalonlyformethotrexateth

2、oseoftheBurkitttype[1_4].1Althoughmethotrexate(MTX)(MTX).Theprimarysettingforpharmacokineticmonitor-isusedinthetreatmentofmanymalignancies,thebenefitofingofMTXisitsuseinhighdoses(HDMTX)foradjuvantusingHDMTX(1g/m2),asopposedtoconventionallydosedtherapyofosteosa

3、rcoma,forsingle-agenttreatmentofMTX(<1g/rn2),hasbeenbetterappreciatedinthetreatmentofintracraniallymphomas,andincombinationtherapyofchildhoodacutelymphocyticleukemia(ALL)andosteosarcomachildhoodleukemiaaswellasadultandpediatricnon-[4-10].Freemanetal.[5]reported

4、thatthesystemicrelapserateHodgkinlymphomas.Typically,HDMTXisinfusedinwasnotablydecreasedinchildrenwithALLtreatedwithdosesof3-15g/m2overaperiodof6-24h.PrecautionsHDMTXcomparedwiththosereceivingconventionallydosedmustbetakentoensureahighurineflowandanalkalineMTX.

5、Subsequently,Evansetal.[4]showedthatacriticalurinepH,soastopreventprecipitationofMTXinurine.relationshipexistedbetweenserumconcentrationsofMTXinPatientswithdecreasedrenalfunction,advancedinage,andchildrenwithALLandtheprobabilityofremaininginremis-takingnonstero

6、idalanti-inflammatorydrugsornephro-sion.Inthelatterstudy,childrenwithALLwhoachievedatoxicagentsareatincreasedriskofdevelopingrenaldys-steady-stateMTXconcentrationof16imoVLhadamuchfunctionduringMTXinfusion,thusbeingplacedathighbetterchanceofremaininginremission

7、vsthosechildrenwithriskfortoxicity.AttheendofHDMTXinfusion,andconcentrationsof16,r.tmol/L.periodicallythereafterfor24-48h,drugconcentrationsareTheoptimalHDMTXdosinginchildhoodALL,however,measuredtoassurethatthedisappearancerateofMTXremainstobedefined.Inthestudi

8、esbyEvansetal.[4],althoughfromplasmaisoccurringatanormalrate.Also,attheendallchildrenreceivedthesamedoseofHDMTX(1g/m2),thereofHDMTXinfusion,thepatientisgivenleucovorin(5-was