Cell cycle status and apoptosis of hematopoietic progenitor cells releasedinto the peripheral blood after taxanes and granulocyte colony-stimulatingfactor 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 h ave evaluated the effects of either paclitaxel or docetaxel both at standar d dosages and followed by granulocyte colony-stimulating factor (G-CSF), on circulating CPC release and function in is patients with advanced breast c ancer who had failed previous anthracycline-based regimens. The reported di fferences in biological behaviour between bone marrow and blood-derived hem atopoietic progenitor cells and the ability of both paclitaxel and docetaxe l to induce apoptosis, prompted us to simultaneously evaluate the cell cycl e perturbations induced on CD34(+) cells. Median CD34(+) peaks were 24 mu l (range: 10-58) in the paclitaxel-treated patients and 39 mu l (range: 17-9 1), respectively, in the patients who received docetaxel. After paclitaxel, the percentage of CD34(+) cells in S-phase was low (bromodeoxyuridine, Brd U, labelling index = 3.4+/-2%) with a concomitant presence of early apoptot ic cells (8.1+/-3%). On the contrary, after docetaxel, the percentage of CD 34(+) cells in S-phase was higher (BrdU labelling index = 14.5+/-4%, p<0.05 vs. paclitaxel), while early apoptotic cells were detected at a similar ra te (8.6+/-3%, p = n.s. vs. paclitaxel). In conclusion, when used at standar d dosages, with respect to paclitaxel + G-CSF, docetaxel + G-CSF is a more satisfactory tool to mobilize CPC and to induce them into the cell cycle. T hese data should be taken into account when combinations of docetaxel with other agents are explored as CPC mobilizing regimens for autografting.