Observations on the effects of cyclophosphamide, phosphoramide mustard and some activated oxazaphosphorines on murine L1210 leukemia

Abstract

The L1210 tumor system was used in vitro and in vivo in comparative studies with activated cyclophosphamide analogs, cyclophosphamide and phosphoramide mustard. All the above compounds gave substantial cell kills (5 logs) of L1210 in vivo at doses that were non-toxic, but slight differences were noted. ASTA Z 7557 had a slight advantage in cure rate over cyclophosphamide when these drugs were given i.v. or i.p. to early tumor (i.p.). However, cyclophosphamide had the advantage in cure rate when drug administration was i.v. to advanced tumor. At equimolar concentrations in vitro ASTA Z 7557 was more cytotoxic than either phosphoramide mustard or acrolein. In vivo, the activated cyclophosphamide derivatives caused some unusual toxicities at therapeutic doses that were not seen with cyclophosphamide. The toxicities manifested as spastic responses and acute deaths on rapid i.v. or i.p. injections and as chronic liver atrophies and fibrosis with i.p. treatment.