Phase I study of weekly paclitaxel in combination with pazopanib and lapatinib in advanced solid malignancies
It has been speculated that weekly paclitaxel enhances antiangiogenesis and, hence, results in a greater inhibition of cancer growth than the 3-week schedule. We compared the weekly and 3-week schedules of paclitaxel in inhibiting angiogenesis, tumor growth and bone marrow hematopoiesis in a lung cancer model. Vehicle or paclitaxel was administered i.p. to three groups of nude mice bearing a human lung cancer. The vehicle was given weekly for six doses or every 3 weeks for two doses (Group A). Paclitaxel was administered at 20 mg/kg/week for six doses (Group B) or 60 mg/kg/3 weeks for two doses (Group C). The tumor growth rate was reduced by 50% equally in both the paclitaxel-treated groups. Intratumoral microvasculature was reduced by 70% in each paclitaxel-treated group. However, white blood cell count was significantly reduced in Group C in comparison with that of Group A or B. We conclude that in this model, angiogenesis and tumor growth were inhibited to the same extent when paclitaxel was administered on a weekly or 3-week schedule. Inhibition of tumor growth by paclitaxel was associated with suppression of angiogenesis. Weekly administration of paclitaxel resulted in a lower degree of leukopenia than with the 3-week schedule, mimicking the clinical setting.