Paclitaxel-containing high-dose chemotherapy: the University of Colorado experience

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is one of the most important antineo-plastic agents developed over the last 20 years. It has proven activity in breast cancer, ovarian cancer, and non-small cell lung cancer. In this study, the possibility of incorporating paclitaxel into a high-dose chemotherapy regimen targeting patients with breast cancer was evaluated. From a widely used regimen composed of cyclophosphamide, cisplatin, and carmustine, carmustine was deleted and paclitaxel added at the beginning of the regimen. The dose of paclitaxel was then escalated until life-threatening toxicities occurred. It was demonstrated that the dose of paclitaxel could be escalated to 775 mg/m2, combined with cyclophosphamide 5,625 mg/m2 and cisplatin 165 mg/m2, followed by autologous hematopoietic progenitor cell support. A phase II study testing this combination in patients with chemotherapy-responsive metastatic breast cancer has been initiated. A new phase I study to test the feasibility of adding carmustine to this paclitaxel-based regimen is currently under way. The status of this study is briefly summarized.