High-Dose Chemotherapy in Childhood Brain Tumors

Abstract

Early attempts to use high-dose chemotherapy technology in order to improve the effect of nitrosurea on high-grade gliomas resulted in minimal benefit as well as in severe toxicity. Since then, other drugs have been applied in conjunction with either autologous bone marrow or peripheral blood stem cells, including thiotepa, etoposide, melphalan, cyclophosphamide, and busulfan. The data suggest benefit in recurrent primitive neuroectodermal tumors (PNET), in newly diagnosed young children with PNET and possibly in young children with newly diagnosed ependymoma, as a strategy not only to improve tumor-free survival but also to avoid exposure of the young brain to irradiation. In other tumors such as recurrent ependymoma and newly diagnosed or recurrent brain stem glioma, high-dose chemotherapy remains ineffective. New protocols under evaluation include new agents, multiple cycles of high-dose chemotherapy and allogeneic transplantation as immunotherapeutic approach.

Combined Biodifferentiating and Antiangiogenic Oral Metronomic Therapy is Feasible and Effective in Relapsed Solid Tumors in Children: Single-Center Pilot Study

“…The outcome of children with metastatic sarcomas, relapsed brain tumors and other high-risk refractory and/or relapsed malignancies remains poor despite the introduction of doseintensified chemotherapy, high-dose chemotherapy and several novel therapeutic approaches, such as monoclonal antibodies and kinase inhibitors [1]. Therefore, treatment strategies which act on multiple levels including tumor cells but also the stromal milieu may be of clinical benefit [2][3][4][5][6].…”

The expected “boomerang effect”?

“…The hypothesis proposed to explain this finding is also fully acceptable. In the time periods considered, CT has been increasingly included in the RT‐based treatment protocols for childhood BT; drugs known for their potential carcinogenic effects such as nitrogen mustards and, more recently, topoisomerase II inhibitors (notably VP16), administered both at conventional and high dosages, have been some of the agents more frequently used 2–4.…”

“…What is next? For the vast majority of childhood malignant CNS tumors, further intensification of conventional therapies are predicted 2–4. Thus, it must be anticipated that the long‐term survival risk for patients with brain tumors of developing SMN will inevitably increase.…”

Neurooncology – Present and Future

“…In adult neurooncology some progress has been made in the treatment of oligodendroglioma, whereas treatment of glioblastoma, the most frequent adult tumor, still remains unsatisfactory. This issue of ONKOLOGIE contains four articles selected out of the broad spectrum of neuroncology focused on pediatric neurooncology [2], primary brain tumors in adulthood [3], brain edema [4] and paraneoplastic disease [5]. Brain tumors are the most frequent tumor entity in children.…”

“…Although radiation therapy is effective in many of these tumors, evidence is increasing that the brain tissue of children can be compromised by radiation therapy and late sequelae must be expected. The publication of Wolff and Finlay [2] discusses high-dose chemotherapies in pediatric brain tumors, it also comments on several tumor entities and their response to therapy. In brain stem gliomas and recurrences of ependymomas, unfortunately the therapies are not very effective.…”