Heike Daldrup-Link

Publication Details

  • Dose Escalation Study of No-Carrier-Added I-131-Metaiodobenzylguanidine for Relapsed or Refractory Neuroblastoma: New Approaches to Neuroblastoma Therapy Consortium Trial JOURNAL OF NUCLEAR MEDICINE Matthay, K. K., Weiss, B., Villablanca, J. G., Maris, J. M., Yanik, G. A., DuBois, S. G., Stubbs, J., Groshen, S., Tsao-Wei, D., Hawkins, R., Jackson, H., Goodarzian, F., Daldrup-Link, H., Panigrahy, A., Towbin, A., Shimada, H., Barrett, J., LaFrance, N., Babich, J. 2012; 53 (7): 1155-1163


    (131)I-metaiodobenzylguanidine (MIBG) is specifically taken up in neuroblastoma, with a response rate of 20%-37% in relapsed disease. Nonradioactive carrier MIBG molecules inhibit uptake of (131)I-MIBG, theoretically resulting in less tumor radiation and increased risk of cardiovascular toxicity. Our aim was to establish the maximum tolerated dose of no-carrier-added (NCA) (131)I-MIBG, with secondary aims of assessing tumor and organ dosimetry and overall response.Eligible patients were 1-30 y old with resistant neuroblastoma, (131)I-MIBG uptake, and cryopreserved hematopoietic stem cells. A diagnostic dose of NCA (131)I-MIBG was followed by 3 dosimetry scans to assess radiation dose to critical organs and soft-tissue tumors. The treatment dose of NCA (131)I-MIBG (specific activity, 165 MBq/?g) was adjusted as necessary on the basis of critical organ tolerance limits. Autologous hematopoietic stem cells were infused 14 d after therapy to abrogate prolonged myelosuppression. Response and toxicity were evaluated on day 60. The NCA (131)I-MIBG was escalated from 444 to 777 MBq/kg (12-21 mCi/kg) using a 3 + 3 design. Dose-limiting toxicity (DLT) was failure to reconstitute neutrophils to greater than 500/?L within 28 d or platelets to greater than 20,000/?L within 56 d, or grade 3 or 4 nonhematologic toxicity by Common Terminology Criteria for Adverse Events (version 3.0) except for predefined exclusions.Three patients each were evaluable at 444, 555, and 666 MBq/kg without DLT. The dose of 777 MBq/kg dose was not feasible because of organ dosimetry limits; however, 3 assigned patients were evaluable for a received dose of 666 MBq/kg, providing a total of 6 patients evaluable for toxicity at 666 MBq/kg without DLT. Mean whole-body radiation was 0.23 mGy/MBq, and mean organ doses were 0.92, 0.82, and 1.2 mGy/MBq of MIBG for the liver, lung, and kidney, respectively. Eight patients had 13 soft-tissue lesions with tumor-absorbed doses of 26-378 Gy. Four of 15 patients had a complete (n = 1) or partial (n = 3) response, 1 had a mixed response, 4 had stable disease, and 6 had progressive disease.NCA (131)I-MIBG with autologous peripheral blood stem cell transplantation is feasible at 666 MBq/kg without significant nonhematologic toxicity and with promising activity.

    View details for DOI 10.2967/jnumed.111.098624

    View details for Web of Science ID 000306164600033

    View details for PubMedID 22700000

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