Cell cycle status and apoptosis of hematopoietic progenitor cells released into the peripheral blood after taxanes and granulocyte colony-stimulating factor in breast cancer patients

Paclitaxel and its analogue docetaxel show a significant antitumor activity, particularly evident in breast cancer. Paclitaxel has also been proved to be effective as a peripheral blood progenitor cell (CPC) mobilizing agent. To optimize the use of active, disease-specific drugs as CPC priming, we have evaluated the effects of either paclitaxel or docetaxel both at standard dosages and followed by granulocyte colony-stimulating factor (G-CSF), on circulating CPC release and function in 18 patients with advanced breast cancer who had failed previous anthracycline-based regimens. The reported differences in biological behaviour between bone marrow and blood-derived hematopoietic progenitor cells and the ability of both paclitaxel and docetaxel to induce apoptosis, prompted us to simultaneously evaluate the cell cycle perturbations induced on CD34⁺ cells. Median CD34⁺ peaks were 24 μl (range: 10-58) in the paclitaxel-treated patients and 39 μl (range: 17-91), respectively, in the patients who received docetaxel. After paclitaxel, the percentage of CD34⁺ cells in S-phase was low (bromodeoxyuridine, BrdU, labelling index = 3.4±2%) with a concomitant presence of early apoptotic cells (8.1±3%). On the contrary, after docetaxel, the percentage of CD34⁺ cells in S-phase was higher (BrdU labelling index = 14.5±4%, p