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    Neuroblastoma Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Recurrent Neuroblastoma

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    Treatment options for recurrent or refractory neuroblastoma in patients initially classified as high risk include the following:

    1. Chemotherapy.
    2. Iodine 131-mIBG (131 I-mIBG) alone, in combination with other therapy, or followed by stem cell rescue.
    3. Second autologous stem cell transplantation (SCT) after retrieval chemotherapy. (Refer to the Autologous Hematopoietic Cell Transplantation section in the PDQ summary on Childhood Hematopoietic Cell Transplantation for more information about transplantation.)

    It is not known whether one therapeutic approach is superior to another.

    Evidence (chemotherapy):

    1. Topotecan in combination with cyclophosphamide or etoposide has been used in patients with recurrent disease who did not receive topotecan initially.[11,12]; [10][Level of evidence: 1A]
    2. The combination of irinotecan and temozolomide had a 15% response rate in one study.[13][Level of evidence: 2A]
    3. High-dose carboplatin, irinotecan, and/or temozolomide has been used in patients resistant or refractory to regimens containing topotecan.[12]
    4. A retrospective study reported on 74 patients who received 92 cycles of ifosfamide, carboplatin, and etoposide, included 37 patients who received peripheral blood stem cell rescue following response to this drug combination.[14]
      • Disease regressions (major and minor responses) were achieved by 14 of 17 patients (82%) with a new relapse, 13 of 26 patients (50%) with refractory neuroblastoma, and 12 of 34 patients (35%) who were treated for progressive disease during chemotherapy (P = .005).
      • Grade 3 toxicities were rare.

    Evidence (131 I-mIBG):

    1. For children with recurrent or refractory neuroblastoma, 131 I-mIBG is an effective palliative agent and may be considered alone or in combination with chemotherapy (with stem cell rescue) in a clinical research trial.[15,16,17,18,19]; [20,21][Level of evidence: 3iiiA]

    Evidence (second autologous SCT following retrieval chemotherapy):

    1. Second autologous stem cell transplantation (SCT) after retrieval chemotherapy may be considered, particularly in the setting of a clinical trial. (Refer to the Autologous Hematopoietic Cell Transplantation section in the PDQ summary on Childhood Hematopoietic Cell Transplantation for more information about transplantation.)
    2. Data from three consecutive German high-risk neuroblastoma trials described 253 children relapsing after intensive chemotherapy with autologous SCT who had a 5-year OS rate of less than 10%. Only 23 of the 253 patients eventually proceeded to a second autologous SCT following retrieval chemotherapy.[22][Level of evidence: 3iiiA]
      • Among these patients, the 3-year OS rate was 43%, but the 5-year OS rate was less than 20%.
      • This shows that intensive second-line therapy is feasible, although even with intensive therapy and second autologous SCT, only a small minority of relapsed high-risk neuroblastoma patients may benefit.
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