1.3 Bis-(2 chloroethyl)-1-nitrosourea and streptozotocin chemotherapy

Streptozotocin (STZ) was combined with 1,3 bis-(2 chloroethyl)-1-nitrosourea (BCNU) and with BCNU and 5-fluorouracil (FU) in a 2- and 3-drug clinical chemotherapeutic trail. The premise that STZ and BCNU are qualitatively different with regard to marrow suppression was the primary rationale of the study. The 2- and 3-drug regimes were associated with a higher incidence of severe leukopenia and thrombopenia (47% and 100%, respectively) and a lower mean nadir for each (1,700/mm3 and 15,000/mm3) than the reported experience with single drug BCNU therapy. However, this synergism did not apply to therapeutic effects. The reasons for potentiation of marrow toxicity may be related to specific aspects of direct drug interaction as well as alterations in pharmacologic reactions.