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Phase I Study of Targeted Radioimmunotherapy for Leptomeningeal Cancers Using Intra-Ommaya 131-I-3F8
Article Abstract by:
ferrab
Original Author: Kim Kramer
Purpose
TumorsmetastasizingtotheCNSandlep tomeninges(LM)areassociatedwithsigni?cant
mortality.Wetestedthetoxicity,pharmacokin
etics,anddosimetryofintraventriculariodine- 131ñ
131
I-3F8)targetingGD2-positiveC NS/LMdiseaseinaphaseI
labeledmonoclonala ntibody3F8(
clinicaltrial.
Patientsan dMethods
AdequateCSF?owwasdeterminedbypr etreatmentindium-111-DTPAstudies.Fifteen
patientsreceivedatracer(1to2mCi)andtherapeuticinjection(10to20mCi)ofintra-Ommaya
131131
I-3F8. I-3F8pharmacokineticswerestudiedbyserialCSFa ndbloodsamplings.
Dosimetrywasbasedonpha rmacokineticsandregionofinterest(ROI)analys esonwhole-
bodygammacamerascans.Tumorres ponsewasdeterminedbyclinical,radiographic,and
cytologiccriteria.
Results
Totalabsorbed CSF dose was 1.12 to 13.00 Gy by sampling and 1.00 to 13.70Gy by ROI data.
Average dosimetry ratio (Gy/mCi) of the therapy /tracer administration was 0.88 ( 0.58) and 1.08 ( 0.66) based on CSF pharmacokinetics and ROI analysis, respectively. CSF half-life by sampling was 3 to 12.9 hours. Toxicities included self-limited headache, fever, and vomiting. Dose-limiting toxicity was reached at the 20-mCi dose,when transient elevations in intracranial pressure and chemical meningitis were seen.Threeof13assessable patients achieved objective radiographic and/or cytologic responses. No late toxicities have been seen in two patients who remain in remission off therapy for more than 3.5 years.
Conclusion
131I-3F8 was generally well tolerated; the maximum-tolerated dose was10
Intra-Ommaya mCi.AhighCSF-to-blood ratio was achieved.Tracer studies reliably predicted the therapeutic
dosetotheCSF.Radioimmunoconju gatestargetingGD2mayhaveclinicalutilityinthetreatment
Published: December 05, 2007