Phase I Study of Targeted Radioimmunotherapy for Leptomeningeal Cancers Using Intra-Ommaya 131-I-3F8
| Autor: | Pat Zanzonico, Samuel D. Yeh, John L. Humm, Kim Kramer, William L. Gerald, Yasmin Khakoo, Steven M. Larson, Henry W. Yeung, Mark M. Souweidane, Ronald D. Finn, Ira J. Dunkel, Nai-Kong V. Cheung, Suzanne L. Wolden |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Cancer Research Adolescent medicine.medical_treatment Phases of clinical research Iodine Radioisotopes Antibodies Monoclonal Murine-Derived Mice Neuroblastoma Pharmacokinetics Region of interest Meningeal Neoplasms Animals Humans Dosimetry Medicine Cerebellar Neoplasms Child Radionuclide Imaging Mice Inbred BALB C business.industry Immunotoxins Antibodies Monoclonal Infant Cancer Middle Aged Radioimmunotherapy medicine.disease Radiation therapy Oncology Child Preschool Immunoglobulin G Monoclonal business Nuclear medicine Medulloblastoma |
| Zdroj: | Journal of Clinical Oncology. 25:5465-5470 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2007.11.1807 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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