Antitumor effectiveness of bolus versus split dose vinblastine treatment in EAT tumors in mice

Vinblastine (VELBE) is one of the first chemotherapeutic agents used in the treatment of malignancies. To explore the effectiveness of various treatment regimens, bolus versus 24-hour continuous VELBE treatment was tested on an EAT tumor model in mice. Continuous VELBE infusion was simulated by splitting the bolus VELBE dose into 4 fractions, injected at 8-hour intervals. A comparison of antitumor effectiveness between bolus and split dose VELBE treatment was determined by three assays: cell survival, tumor growth delay and animal survival. The cell survival curves of both bolus and split dose VELBE treatments indicated a biphasic response with an initial fast reduction in cell survival followed by a plateau. However, split dose treatment was significantly more effective than bolus treatment at all doses tested (p < 0.001). Tumor growth delay of the split dose VELBE treatment was 6.9 days and of the bolus VELBE treatment 3.0 days, indicating that the split dose treatment is approximately 2-times more effective (p < 0.001). Median survival time of mice treated with split VELBE dose (24.0 days) was significantly longer compared to that of mice treated with bolus VELBE dose (16.5 days) (p < 0.001). The median survival time of control untreated mice (16.0 days) and bolus treated mice did not differ (p = 0.24). Our study shows that at the same VELBE dose the split dose VELBE treatment is more effective than VELBE administered in bolus.