Optimum time sequence for the administration of cyclophosphamide and other drugs in vivo.

The significance of time interval for administration of a second drug after a first dose of cyclophosphamide (CTX) was studied for a human ovarian, lung, and colon carcinoma line growing as xenografts in nude mice. The effects of combination of two drugs were found to be dependent on the interval between the administration of each drug. The most effective chemotherapy schedules were those in which adriamycin (ADM) or CTX were sequenced to coincide with the time point where the tumour was regrowing from the single dose of CTX. The variation of the cell kinetic parameters, as estimated by flow cytometry analysis, could not be correlated with the antitumour action of the drug combination.