Use of synchronization induced by cyclophosphamide in a methylcholanthrene sarcoma with circadian proliferation to rational sequential chemotherapy.

Owing to the circadian activity of tumoral proliferation, cyclophosphamide (CPA) morning injection exerts, on a methylcholanthrene induced sarcoma, a preferential oncostatic effect. This morning injection is followed by a temporary inhibition of mitoses preceding a high mitotic peak, explained by chemo-induced synchronization of tumor cells. Whereas single vinblastine (VLB) administration has no antitumoral effect, an injection of VLB during the described peak is able to improve oncostatic effect of cyclophosphamide. Moreover, the VLB administration at the same moment as CPA suppresses antineoplastic activity of the latter.