High-dose chemotherapy for recurrent medulloblastoma: time for a reappraisal.

M ore than a decade ago, Finlay et al. published a landmark article in which they demonstrated that a subset of patients with recurrent brain tumors of diverse histologic diagnosis could be salvaged with high-dose chemotherapy followed by autologous stem cell rescue. The preparatory regimen included only 2 drugs: thiotepa and etoposide. Hematopoietic growth factors were used to enhance count recovery. Observations from this early series suggested that patients with minimal residual disease at the time of high-dose chemotherapy may be the appropriate candidates for this retrieval strategy. Patients with bulky, metastatic recurrent disease or disease that has not responded to retrieval chemotherapy may not be the best candidates for this intervention. The toxicity of this approach was also a concern in this early series. Overall, 5 of the 45 patients (11%) were long-term survivors and all of them had highgrade gliomas. Subsequent publications from these and other investigators have further defined the role of high-dose chemotherapy in patients with recurrent medulloblastoma. Dunkel et al. suggested that patients treated with prior combined modality therapy (ie, radiotherapy and chemotherapy) had a worse outcome compared with patients who were treated with chemotherapy only (25 6 15% vs 43 6 16%). In the series by Gururangan et al., 12 of the 20 patients (60%) were irradiated after high-dose chemotherapy and autologous bone marrow rescue and 7 of these 12 patients were long-term survivors. Taken together, these data suggest that a select group of patients may be able to achieve durable disease control; this subgroup consists of young patients treated with chemotherapy alone as initial therapy followed by high-dose chemotherapy and radiotherapy at the time of disease recurrence. In a large prospective French series, infants with local recurrences of medulloblastoma after initial treatment with surgical resection and chemotherapy alone could be salvaged with surgical resection, high-dose chemotherapy, and radiotherapy. In contrast, patients with metastatic recurrent disease had a much worse outcome. See referenced original article on pages 1805 11, this issue.