Treatment of High-Risk Neuroblastoma
Standard Treatment Options
Patients classified as high risk receive treatment with an aggressive regimen of combination chemotherapy consisting of very high drug doses, generally termed induction. Drugs often used include cyclophosphamide, ifosfamide, cisplatin, carboplatin, vincristine, doxorubicin, etoposide, and topotecan. COG has completed a pilot study of induction demonstrating the feasibility of substituting two cycles of topotecan and cyclophosphamide for two cycles of vincristine, cyclophosphamide, and doxorubicin. After a response to chemotherapy, resection of the primary tumor should be attempted, followed by myeloablative chemotherapy and stem cell rescue (i.e., bone marrow and/or peripheral blood stem cell transplantation). Whether or not harvested stem cells should be purged of neuroblastoma cells has been studied in a randomized fashion. There was no advantage to purging. Two or more sequential cycles of myeloablative chemotherapy and stem cell rescue given in a tandem fashion has been studied and feasibility was established.[7,18] It is now under clinical evaluation in COG. Radiation to the primary tumor site should be undertaken whether or not a complete excision was obtained. The optimal dose of radiation therapy has not been determined. Radiation of sites of metastatic disease is determined on an individual case basis. After recovery, patients are treated with oral 13-cis -retinoic acid for 6 months. Both myeloablative therapy and postchemotherapy retinoic acid improve outcome in patients categorized as high risk.[3,5] For high risk-patients in remission following HSCT, compared to retinoic acid alone, chimeric anti-GD2 antibody ch14.18 combined with granulocyte-macrophage colony stimulating factor and interleukin-2 and given in concert with retinoic acid improves EFS.
Treatment Options Under Clinical Evaluation
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-ANBL0532: The COG is studying, in a randomized fashion, whether two cycles of myeloablative chemotherapy and stem cell transplantation is superior to a single cycle of myeloblative chemotherapy and stem cell transplantation. In addition, in the same patients in a nonrandomized fashion, they are studying whether substitution of two cycles of topotecan and cyclophosphamide for two cycles of vincristine, cyclophosphamide, and doxorubicin improves outcome. Patients with residual primary tumor will also receive higher doses of radiation than previously given in COG studies.[7,18]
COG-ANBL0032 and COG-ANBL0931: The COG is studying, in a nonrandomized fashion, the use of monoclonal antibody therapy with granulocyte-macrophage colony-stimulating factor and interleukin-2 combined with cis -retinoic acid following chemotherapy.[6,19,20]
- The New Approaches to Neuroblastoma Therapy (NANT) consortium is studying inclusion of myelobablative doses of iodine-131-meta-iodobenzylguanidine (MIBG) with myeloablative chemotherapy prior to stem cell transplantation in patients with an incomplete response to induction chemotherapy (NANT-2004-06).[21,22]