Phase I study of targeted radioimmunotherapy for leptomeningeal cancers using intra-Ommaya 131-I-3F8 Journal Article

Authors: Kramer, K.; Humm, J. L.; Souweidane, M. M.; Zanzonico, P. B.; Dunkel, I. J.; Gerald, W. L.; Khakoo, Y.; Yeh, S. D.; Yeung, H. W.; Finn, R. D.; Wolden, S. L.; Larson, S. M.; Cheung, N. K. V.
Article Title: Phase I study of targeted radioimmunotherapy for leptomeningeal cancers using intra-Ommaya 131-I-3F8
Abstract: Purpose: Tumors metastasizing to the CNS and leptomeninges (LM) are associated with significant mortality. We tested the toxicity, pharmacokinetics, and dosimetry of intraventricular iodine-131-labeled monoclonal antibody 3F8 (131I-3F8) targeting GD2-positive CNS/LM disease in a phase I clinical trial. Patients and Methods: Adequate CSF flow was determined by pretreatment indium-111-DTPA studies. Fifteen patients received a tracer (1 to 2 mCi) and therapeutic injection (10 to 20 mCi) of intra-Ommaya 131I-3F8. 131I-3F8 pharmacokinetics were studied by serial CSF and blood samplings. Dosimetry was based on pharmacokinetics and region of interest (ROI) analyses on whole-body gamma camera scans. Tumor response was determined by clinical, radiographic, and cytologic criteria. Results: Total absorbed CSF dose was 1.12 to 13.00 Gy by sampling and 1.00 to 13.70 Gy 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. Three of 13 assessable 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: Intra-Ommaya 131I-3F8 was generally well tolerated; the maximum-tolerated dose was 10 mCi. A high CSF-to-blood ratio was achieved. Tracer studies reliably predicted the therapeutic dose to the CSF. Radioimmunoconjugates targeting GD2 may have clinical utility in the treatment of CNS/LM malignancies. © 2007 by American Society of Clinical Oncology.
Keywords: adolescent; adult; child; clinical article; treatment response; aged; child, preschool; middle aged; unclassified drug; clinical trial; side effect; drug targeting; nuclear magnetic resonance imaging; antineoplastic agent; animals; mice; melanoma; bone marrow suppression; vomiting; bone pain; bradycardia; retinoblastoma; mice, inbred balb c; backache; fever; hyponatremia; antibodies, monoclonal; immunoglobulin g; iodine radioisotopes; cerebrospinal fluid; infant; meningeal neoplasms; neuroblastoma; dosimetry; medulloblastoma; ependymoma; headache; phase 1 clinical trial; drug half life; radioimmunotherapy; single photon emission computer tomography; cerebellar neoplasms; neuroectoderm tumor; meningitis; leg pain; pentetate indium in 111; monoclonal antibody 3f8 i 131; rhabdoid tumor; immunotoxins; intracranial pressure
Journal Title: Journal of Clinical Oncology
Volume: 25
Issue: 34
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2007-12-01
Start Page: 5465
End Page: 5470
Language: English
DOI: 10.1200/jco.2007.11.1807
PUBMED: 18048828
PROVIDER: scopus
Notes: --- - "Cited By (since 1996): 27" - "Export Date: 17 November 2011" - "CODEN: JCOND" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Samuel D J Yeh
    105 Yeh
  2. Nai-Kong Cheung
    588 Cheung
  3. Ira J Dunkel
    324 Dunkel
  4. Kim Kramer
    207 Kramer
  5. Yasmin Khakoo
    131 Khakoo
  6. Suzanne L Wolden
    503 Wolden
  7. Henry W D Yeung
    126 Yeung
  8. Ronald D Finn
    278 Finn
  9. William L Gerald
    375 Gerald
  10. John Laurence Humm
    393 Humm
  11. Pat B Zanzonico
    313 Zanzonico
  12. Steven M Larson
    918 Larson