Paclitaxel dose intensity.

Abstract

Paclitaxel is effective in the treatment of cancer of the ovary and cancer of the breast, as well as other malignancies. We have analyzed available phase II data in these two diseases, to assess the possibility that paclitaxel dose intensity may be important in the induction of disease response. When analyzed by the methods developed by Hrynuik and Levin, available data suggest that the relationship between objective disease response and paclitaxel dose intensity in recurrent cancer of the ovary is strongly statistically significant with a two-sided p value of 0.022. Available data suggest that the relationship in breast cancer is even stronger, with a two-sided p value of 0.004. In both diseases, optimal results have been observed at the dose schedule of 250 mg/m2/21 days, given as a 24 hour IV infusion. We have also performed an analysis comparing the only two prospective randomized studies that examined the potential role of dose intensity for this drug in cancer of the ovary. At 135 mg/m2/21 days, the objective response rate was 13.2%; and at 250 mg/m2/21 days, the objective response rate was 35.9%. The response rate seen at the intermediate dose of 175 were intermediate to 135 and 250; and linear regression analysis shows a correlation coefficient for these data of 0.946. Since flexible cytokine support may be essential in maintaining paclitaxel dose intensity, we have also discussed this approach as well as the paclitaxel dosing strategy that is associated with optimal clinical results in recurrent cancer of the ovary.