phalan, cyclophosphamide (4-hydroperoxycyclophosphamide in vitro), iphosphamide (4-hydroperoxyiphosphamide in vitro), phenylketocyclo

tion of our model to study medulloblastoma, and subsequent studies have indicated significant efficacy of the classical al kylators cyclophosphamide and melphalan against the human medulloblastoma cell line TE-671 growing s.c. and intracra nially in athymic mice (18—21). We now extend these observa tions and report the in vitro and in vivo sensitivity of TE-671 to sevenclassicalalkylators. Agents studied included melphalan (NSC 8806), cyclophosphamide (NSC 26271) (4-hydroperox ycyclophosphamide in vitro), iphosphamide (NSC 10924) (4hydroperoxyiphosphamide in vitro), thio-TEPA3 (NSC 6396), the 4-thiocyclophosphamide derivative Asta Z 7557 (22), and phenylketocyclophosphamide and phenylketoiphosphamide, two novel analogues of the aldehydic metabolites of cyclophos phamide and iphosphamide, respectively (23). All agents were active, with melphalan demonstrating the most activity in vitro and in vivo. Further studies comparing cyclophosphamide and phenylketocyclophosphamide demonstrated the greater lipo philicity and toxicity (following i.p. administration) of phenyl ketocyclophosphamide, as well as the potential means to ther apeutically exploit these differences.