The development of the oxazaphosphorine cytostatics, cyclophosphamide, ifosfamide and trofosfamide was based on the idea of extending the transport from/active from principle to the highly reactive nitrogen mustard group. In a critical analysis and synopsis of the available findings and knowledge, the question of the extent to which the hypotheses on which this concept is based have been confirmed in experiments and in clinical practice is investigated. From the chemical and synthetic viewpoint, the intended conversion of the reactive nitrogen mustard into an inactive transport from (latentiation) has been achieved. The requirement of enzymatic activation of the transport form in the target organ (the cancer cell) has been achieved by a sequential series of various metabolic reactions and has been proven. The objective of a substantial increase in the therapeutic range of alkylating agents has been achieved with the development of the oxazaphosphorine cytostatics. The high cancerotoxic selectivity of these compounds is closely linked with the cytostatic specificity of their activated primary metabolites. A further increase in the cancerotoxic selectivity of oxazaphosphorines has been achieved by the development of mesna as a regional uroprotector. Mesna eliminates the danger of therapy-limiting urotoxic side effects of oxazaphosphorines. Under mesna protection oxazaphosphorines can be used at higher dosages and with greater safety and their therapeutic efficacy can be increased.
