Upfront treatment of high-risk neuroblastoma with a combination of 131I-MIBG and topotecan.

Abstract

BACKGROUND:

(131)I-metaiodobenzylguanidine ((131) I-MIBG) has a significant anti-tumor effect against neuroblastoma (NBL). Topotecan (TPT) can act as a radio-sensitizer and can up-regulate (131) I-MIBG uptake in vitro in NBL.

AIM:

Determine the efficacy of the combination of (131) I-MIBG with topotecan in newly diagnosed high-risk (HR) NBL patients.

METHODS:

In a prospective, window phase II study, patients with newly diagnosed high-risk neuroblastoma were treated at diagnosis with two courses of (131) I-MIBG directly followed by topotecan (0.7 mg/m(2) for 5 days). After these two courses, standard induction treatment (four courses of VECI), surgery and myeloablative therapy (MAT) with autologous stem cell transplantation (ASCT) was given. Response was measured after two courses of (131) I-MIBG-topotecan and post MAT and ASCT. Hematologic toxicity and harvesting of stem cells were analysed. Topoisomerase-1 activity levels were analysed in primary tumor material.

RESULTS:

Sixteen patients were included in the study; median age was 2.8 years. MIBG administered activity (AA) (median and range) of the first course was 0.5 (0.4-0.6) GBq/kg (giga Becquerel/kilogram) and of the second course 0.4 (0.3-0.5) GBq/kg. The overall objective response rate (ORR) after 2 × MIBG/TPT was 57%, the primary tumor RR was 94%, and bone marrow RR was 43%. The ORR post MAT and ASCT was 57%. Hematologic grade four toxicity: after first and second (131) I-MIBG (platelets 25/33%, neutrophils 13/33%, and hemoglobin 25/7%). Topoisomerase-1 activity levels were increased in 10/10 (100%) measured tumors.

CONCLUSIONS:

Combination therapy with MIBG-topotecan is an effective window treatment in newly diagnosed high-risk neuroblastoma patients.

• Authors: Kathelijne C J M Kraal, Godelieve A M Tytgat, Berthe L F van Eck-Smit, Boen Kam, Huib N Caron, Max van Noesel
• Journal: Pediatric blood & cancer (Pediatr Blood Cancer) Vol. 62 Issue 11 Pg. 1886-91 (Nov 2015) ISSN: 1545-5017 [Electronic] United States
• PMID: 25981988 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Wiley Periodicals, Inc.

Chemical References

• 3-Iodobenzylguanidine
• Topotecan

Topics

• 3-Iodobenzylguanidine (administration & dosage)
• Adolescent
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Autografts
• Child
• Child, Preschool
• Combined Modality Therapy (methods)
• Female
• Humans
• Infant
• Infant, Newborn
• Male
• Neuroblastoma (mortality, therapy)
• Prospective Studies
• Risk Factors
• Stem Cell Transplantation
• Topotecan (administration & dosage)
• Transplantation Conditioning