Embryonal
tumors are an aggressive subtype of high-grade, pediatric central nervous system (CNS)
tumors often with dismal survival rates. The 5-year survival for highest-risk embryonal
tumors may be as low as 10 %. We report feasibility and efficacy from our experience using intravenous (IV)
cyclophosphamide concurrently with craniospinal radiation (CSI) in high-risk embryonal CNS
tumors of childhood. Ten consecutive children (aged: 3.5-15.5 years, median: 10.2 years, six male) with high-risk embryonal
tumors, including: large cell/anaplastic
medulloblastoma (6), atypical
teratoid rhabdoid tumor (1), and leptomeningeal
primitive neuroectodermal tumor (3), were treated with IV
cyclophosphamide 1 g/M(2) on days 1 and 2 of CSI. Following a median of 36 Gy CSI plus
tumor boosts, adjuvant treatment consisted of 21 doses of oral
etoposide (7) and
alkylator based
chemotherapy from five to eight cycles in all. Of the ten patients thus treated, six remain alive with no evidence of disease and four are deceased. Median survival was 3.3 years, with a 3-year progression-free survival of 50 % (5/10). Median follow-up was: 3.3 years (range: 5 months-12.9 years) in the five patients with progression, median time-to-progression was: 1.3 years (range: 1 month-3 years). Median follow-up in the patients without progression is 8.8 years (range: 3-12.9 years). Complications due to
adjuvant chemotherapy were typical and included myelosupression (10), necessitating shortened duration of
chemotherapy in three, and
hemorrhagic cystitis (1). In high-risk embryonal CNS
tumors,
cyclophosphamide given concurrently with CSI is well tolerated. Early results suggest that a phase II trial is warranted.