Abstract: |
Innovation in the management of brain metastases is needed. We evaluated the addition of compartmental intrathecal antibody-based radioimmunotherapy (cRIT) in patients with recurrent metastatic central nervous system (CNS) neuroblastoma following surgery, craniospinal irradiation, and chemotherapy. Twenty one patients treated for recurrent neuroblastoma metastatic to the CNS, received a cRIT-containing salvage regimen incorporating intrathecal 131I-monoclonal antibodies (MoAbs) targeting GD2 or B7H3 following surgery and radiation. Most patients also received outpatient craniospinal irradiation, 3F8/GMCSF immunotherapy, 13-cis-retinoic acid and oral temozolomide for systemic control. Seventeen of 21 cRIT-salvage patients are alive 7-74 months (median 33 months) since CNS relapse, with all 17 remaining free of CNS neuroblastoma. One patient died of infection at 22 months with no evidence of disease at autopsy, and one of lung and bone marrow metastases at 15 months, and one of progressive bone marrow disease at 30 months. The cRIT-salvage regimen was well tolerated, notable for myelosuppression minimized by stem cell support (n = 5), and biochemical hypothyroidism (n = 5). One patient with a 7-year history of metastatic neuroblastoma is in remission from MLL-associated secondary leukemia. This is significantly improved to published results with non-cRIT based where relapsed CNS NB has a median time to death of approximately 6 months. The cRITsalvage regimen for CNS metastases was well tolerated byyoung patients, despite their prior history of intensive cytotoxic therapies. It has the potential to increase survival with better than expected quality of life. © Springer Science+Business Media, LLC. 2009. |
Keywords: |
adolescent; adult; child; clinical article; treatment outcome; aged; child, preschool; middle aged; leukemia; cancer surgery; retrospective studies; young adult; unclassified drug; overall survival; clinical trial; drug tolerability; salvage therapy; cisplatin; doxorubicin; diarrhea; multimodality cancer therapy; side effect; drug targeting; combined modality therapy; temozolomide; recurrent cancer; carboplatin; unindexed drug; cancer immunotherapy; infection; multiple cycle treatment; bone marrow suppression; etoposide; nausea; radiotherapy dosage; drug administration schedule; lorazepam; granulocyte macrophage colony stimulating factor; creatinine; cyclophosphamide; melphalan; vincristine; allogenic bone marrow transplantation; clinical protocol; creatinine blood level; cancer mortality; growth hormone; ifosfamide; thiotepa; short stature; time factors; central nervous system neoplasms; irinotecan; monoclonal antibody; aminotransferase blood level; drug dose escalation; drug fever; cause of death; drug induced headache; survival time; lung metastasis; antibodies, monoclonal; myeloablative conditioning; neuroblastoma; ganglioside gd2; dosimetry; paracetamol; cognition; outpatient; cancer relapse; cataract; idiopathic thrombocytopenic purpura; second cancer; somnolence; hypothyroidism; aminotransferase; isotretinoin; radioimmunotherapy; lung infection; peripheral blood stem cell transplantation; glycoprotein; liothyronine; thyroid hormone; injections, spinal; monoclonal antibody 3f8; monoclonal antibody 3f8 i 131; meningeal metastasis; protein b7 h3; leukemia remission; diphenhydramine; tomography, emission-computed, single-photon; central nervous system metastasis; cns metastases; granulocyte-macrophage colony-stimulating factor; intrathecal; monoclonal antibody 8h9 i 131; potassium iodide; bone marrow metastasis; compartmental radioimmunotherapy
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