Schedule-dependency of Doxorubicin and Vinblastine in EAT tumours in mice

Abstract

Background. Antitumour schedule-dependency of the doxorubicin and vinblastine combination was explored.

Materials and methods. Intraperitoneal Ehrlich ascites tumours (EAT) syngeneic to CBA mice were treated with vinblastine or doxorubicin alone, or in combined treatment schedules.

Results. Combinations of doxorubicin and vinblastine administered at 48-h, but not at 24-h interval, regardless of the sequence of drugs, significantly reduced the number of tumour cells in the ascites in comparison with all other treatments. In the combined treatment schedules, the predominant morphological changes as well as DNA distribution pattern were dependent on the first drug applied. Regardless of the sequence of the drugs, median survival times of animals did not significantly differ between the treatment groups.

Conclusions. The effect of combination of vinblastine and doxorubicin is schedule-dependent. The time interval, but not the sequence of drugs seems to be crucial for the observed effect. The data from preclinical studies are important for planning combined treatment schedules in clinical setting.