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


    Recurrent Neuroblastoma in the Central Nervous System

    Central nervous system (CNS) involvement, although rare at initial presentation, may occur in 5% to 10% of patients with recurrent neuroblastoma. Because upfront treatment for newly diagnosed patients does not adequately treat the CNS, the CNS has emerged as a sanctuary site leading to relapse.[23,24] CNS relapses are almost always fatal, with a median time to death of 6 months.

    Treatment options for recurrent neuroblastoma in the CNS include the following:

    1. Surgery and radiation therapy.
    2. Novel therapeutic approaches.

    Current treatment approaches generally include eradicating bulky and microscopic residual disease in the CNS and minimal residual systemic disease that may herald further relapses. Neurosurgical interventions serve to decrease edema, control hemorrhage, and remove bulky tumor before starting therapy. Compartmental radioimmunotherapy using intrathecal radioiodinated monoclonal antibodies has been tested in patients with recurrent metastatic CNS neuroblastoma after surgery, craniospinal radiation therapy, and chemotherapy.[7]

    Treatment Options Under Clinical Evaluation for Recurrent or Refractory Neuroblastoma

    The following are examples of national and/or institutional clinical trials that are currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.

    • COG-ANBL1221 (NCT01767194) (A Phase II Randomized Trial of Irinotecan/Temozolomide with Temsirolimus or Chimeric 14.18 Antibody [ch14.18] in Children with Refractory, Relapsed, or Progressive Neuroblastoma): This "Pick the Winner" phase II study is designed to compare the response rates and progression-free survival for patients with refractory, relapsed, or progressive neuroblastoma receiving temsirolimus or ch14.18 in combination with irinotecan and temozolomide. Patients more than 365 days of age who have progressed from INSS stage 1, 2, or 4S and have received no chemotherapy or only one cycle of chemotherapy are eligible for this trial.
    • NANT N2011-04 (NCT01711554) (Lenalidomide and Monoclonal Antibody With or Without Isotretinoin in Treating Younger Patients With Refractory or Recurrent Neuroblastoma): This study is to determine the maximum tolerated dose and/or recommended phase II dose of lenalidomide in combination with fixed doses of ch14.18 given intravenously for 4 days (days 8-11) and isotretinoin given twice each day orally for 14 days (days 15-28) and repeated every 28 days to children with refractory or recurrent neuroblastoma.
    • NCT00911560 (Bivalent Vaccine With Escalating Doses of the Immunological Adjuvant OPT-821, in Combination With Oral Beta-Glucan for High-Risk Neuroblastoma): The purpose of this study is to test the safety of a vaccine against neuroblastoma and its effect on cancer.
    • Studies with the ALK inhibitor crizotinib include the following: COG-ADVL0912 (NCT00939770), a phase I and II study of PF-02341066, an oral small molecule inhibitor of anaplastic lymphoma kinase (ALK) and C-met, in children with relapsed/refractory solid tumors and anaplastic large cell lymphoma; and ADVL1212 (NCT01606878), a phase I study of crizotinib in combination with conventional chemotherapy for relapsed or refractory solid tumors or anaplastic large cell lymphoma.
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