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Feasibility and Response to Induction Chemotherapy Intensified With High-Dose Methotrexate for Young Children With Newly Diagnosed High-Risk Disseminated Medulloblastoma

From the Divisions of Pediatric Oncology; Neuroradiology; Neuropathology; and Pediatric Neurosurgery, New York University Medical Center, New York, NY.

Address reprint requests to Susan Chi, MD, Dana-Farber Cancer Institute, 44 Binney St, SW331, Boston, MA 02115; e-mail: susan_chi{at}dfci.harvard.edu

PURPOSE: To evaluate the feasibility of and response rate to an intensified induction chemotherapy regimen for young children with newly diagnosed high-risk or disseminated medulloblastomas.

PATIENTS AND METHODS: From January 1997 to March 2003, 21 patients with high-risk or disseminated medulloblastoma were enrolled. After maximal surgical resection, patients were treated with five cycles of vincristine (0.05 mg/kg/wk x three doses per cycle for three cycles), cisplatin (3.5 mg/kg per cycle), etoposide (4 mg/kg/d x 2 days per cycle), cyclophosphamide (65 mg/kg/d x 2 days per cycle) with mesna, and methotrexate (400 mg/kg per cycle) with leucovorin rescue. Following induction chemotherapy, eligible patients underwent a single myeloablative chemotherapy cycle with autologous stem-cell rescue.

RESULTS: Significant toxicities of this intensified regimen, including gastrointestinal and infectious toxicities, are described. Among the 21 patients enrolled, there were 17 complete responses (81%), two partial responses, one stable disease, and one progressive disease. The 3-year event-free survival and overall survival are 49% (95% CI, 27% to 72%) and 60% (95% CI, 36% to 84%), respectively.

CONCLUSION: This intensified induction chemotherapy regimen is feasible and tolerable. With the majority of patients with disseminated medulloblastoma having M2 or M3 disease at diagnosis, the encouraging high response rate of this intensified induction regimen suggests that such an addition of methotrexate should be explored in future studies.

Portions of this study were presented at the International Society of Pediatric Oncology (SIOP) in Porto, Portugal, September 2002, and at the 10th and 11th International Symposia on Pediatric Neuro-Oncology (ISPNO) in London, England, June 2002, and Boston, MA, June 2004.

Authors' disclosures of potential conflicts of interest are found at the end of this article.