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Topotecan-vincristine-doxorubicin in stage 4 high risk neuroblastoma patients failing to achieve a complete metastatic response to rapid COJEC : a SIOPEN study

Authors
  • Amoroso, Loredana
  • Erminio, Giovanni
  • Makin, Guy
  • Pearson, Andrew DJ
  • Brock, Penelope
  • Valteau-Couanet, Dominique
  • Castel, Victoria
  • Pasquet, Marlène
  • Laureys, Genevieve
  • Thomas, Caroline
  • Luksch, Roberto
  • Ladenstein, Ruth
  • Haupt, Riccardo
  • Garaventa, Alberto
Publication Date
Jan 01, 2018
Source
Ghent University Institutional Archive
Keywords
Language
English
License
Unknown
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Abstract

Purpose : Metastatic response to induction therapy for high-risk neuroblastoma is a prognostic factor. In the International Society of Paediatric Oncology Europe Neuroblastoma (SIOPEN) HR-NBL-1 protocol, only patients with metastatic complete response (CR) or partial response (PR) with <= three abnormal skeletal areas on iodine 123-metaiodobenzylguanidine ([I-123] mIBG) scintigraphy and no bone marrow disease proceed to high dose therapy (HDT). In this study, topotecan-vincristine-doxorubicin (TVD) was evaluated in patients failing to achieve these criteria, with the aim of improving the metastatic response rate. Materials and Methods : Patients with metastatic high-risk neuroblastoma who had not achieved the SIOPEN criteria for HDT after induction received two courses of topotecan 1.5 mg/m(2)/day for 5 days, followed by a 48-hour infusion of vincristine, 2 mg/m(2), and doxorubicin, 45 mg/m(2). Results : Sixty-three patients were eligible and evaluable. Following two courses of TVD, four (6.4%) patients had an overall CR, while 28 (44.4%) had a PR with a combined response rate of 50.8% (95% confidence interval [CI], 37.9 to 63.6). Of these, 23 patients achieved a metastatic CR or a PR with <= 3 mIBG skeletal areas and no bone marrow disease (36.5%; 95% CI, 24.7 to 49.6) and were eligible to receive HDT. Toxicity was mostly haematological, affecting 106 of the 126 courses (84.1%; 95% CI, 76.5 to 90.0), and dose reduction was necessary in six patients. Stomatitis was the second most common nonhematological toxicity, occurring in 20 patients (31.7%). Conclusion : TVD was effective in improving the response rate of high-risk neuroblastoma patients after induction with COJEC enabling them to proceed to HDT. However, the long-term benefits of TVD needs to be determined in randomized clinical trials.

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