A phase II study of radioimmunotherapy with intraventricular (131)I-3F8 for medulloblastoma Journal Article

Authors: Kramer, K.; Pandit-Taskar, N.; Humm, J. L.; Zanzonico, P. B.; Haque, S.; Dunkel, I. J.; Wolden, S. L.; Donzelli, M.; Goldman, D. A.; Lewis, J. S.; Lyashchenko, S. K.; Khakoo, Y.; Carrasquillo, J. A.; Souweidane, M. M.; Greenfield, J. P.; Lyden, D.; De Braganca, K. D.; Gilheeney, S. W.; Larson, S. M.; Cheung, N. K. V.
Article Title: A phase II study of radioimmunotherapy with intraventricular (131)I-3F8 for medulloblastoma
Abstract: Background: High-risk and recurrent medulloblastoma (MB) is associated with significant mortality. The murine monoclonal antibody 3F8 targets the cell-surface disialoganglioside GD2 on MB. We tested the efficacy, toxicity, and dosimetry of compartmental radioimmunotherapy (cRIT) with intraventricular 131I-labeled 3F8 in patients with MB on a phase II clinical trial. Methods: Patients with histopathologically confirmed high-risk or recurrent MB were eligible for cRIT. After determining adequate cerebrospinal fluid (CSF) flow, patients received 2 mCi (where Ci is Curie) 124I-3F8 or 131I-3F8 with nuclear imaging for dosimetry, followed by up to four therapeutic (10 mCi/dose) 131I-3F8 injections. Dosimetry estimates were based on serial CSF and blood samplings over 48 hr plus region-of-interest analyses on serial imaging scans. Disease evaluation included pre- and posttherapy brain/spine magnetic resonance imaging approximately every 3 months for the first year after treatment, and every 6–12 months thereafter. Results: Forty-three patients received a total of 167 injections; 42 patients were evaluable for outcome. No treatment-related deaths occurred. Toxicities related to drug administration included acute bradycardia with somnolence, headache, fatigue, and CSF pleocytosis consistent with chemical meningitis and dystonic reaction. Total CSF absorbed dose was 1,453 cGy (where Gy is Gray; 350.0–2,784). Median overall survival from first dose of cRIT was 24.9 months (95% confidence interval [CI]:16.3–55.8). Patients treated in radiographic and cytologic remission were at a lower risk of death compared to patients with radiographically measurable disease (hazard ratio: 0.40, 95% CI: 0.18–0.88, P = 0.024). Conclusions: cRIT with 131I-3F8 is safe, has favorable dosimetry to CSF, and when added to salvage therapy using conventional modalities, may have clinical utility in maintaining remission in high-risk or recurrent MB. © 2017 Wiley Periodicals, Inc.
Keywords: adolescent; cancer survival; child; clinical article; preschool child; school child; treatment response; unclassified drug; overall survival; thalidomide; fatigue; histopathology; cancer recurrence; bevacizumab; drug efficacy; drug safety; cancer patient; cancer radiotherapy; cytarabine; temozolomide; neuroimaging; nuclear magnetic resonance imaging; positron emission tomography; follow up; antineoplastic agent; cancer immunotherapy; progression free survival; phase 2 clinical trial; basal cell carcinoma; etoposide; cyclophosphamide; dexamethasone; bradycardia; thiotepa; high risk patient; irinotecan; monoclonal antibody; fever; cancer regression; cancer vaccine; isotope labeling; infant; blood sampling; dosimetry; paracetamol; glioblastoma; medulloblastoma; nausea and vomiting; open study; headache; meningioma; tracer; second cancer; somnolence; radioimmunotherapy; meningitis; liothyronine; monoclonal antibody 3f8 i 131; ceftriaxone; diphenhydramine; cerebrospinal fluid cytology; monoclonal antibody 3f8 i 124; arabinoside; 3f8; cerebrospinal fluid flow; craniospinal irradiation; spine radiography; single photon emission computed tomography; potassium iodide; dystonia; re-irradiation; cns tumors; microangiopathy; pleocytosis; long term survival; maintenance chemotherapy; thecoma; human; male; female; priority journal; article; median survival time; intrathecal therapy; mortality risk; moyamoya disease
Journal Title: Pediatric Blood and Cancer
Volume: 65
Issue: 1
ISSN: 1545-5009
Publisher: Wiley Periodicals, Inc  
Date Published: 2018-01-01
Start Page: e26754
Language: English
DOI: 10.1002/pbc.26754
PROVIDER: scopus
PUBMED: 28940863
Notes: Article -- Export Date: 2 January 2018 -- Source: Scopus
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MSK Authors
  1. Nai-Kong Cheung
    439 Cheung
  2. Ira J Dunkel
    251 Dunkel
  3. David C Lyden
    83 Lyden
  4. Kim Kramer
    168 Kramer
  5. Yasmin Khakoo
    99 Khakoo
  6. Suzanne L Wolden
    419 Wolden
  7. Sofia S Haque
    72 Haque
  8. John Laurence Humm
    339 Humm
  9. Pat B Zanzonico
    246 Zanzonico
  10. Jason S Lewis
    242 Lewis
  11. Steven M Larson
    762 Larson