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 microl (range: 10-58) in the paclitaxel-treated patients and 39 microl (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<0.05 vs. paclitaxel), while early apoptotic cells were detected at a similar rate (8. 6+/-3%, p = n.s. vs. paclitaxel). In conclusion, when used at standard 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. These data should be taken into account when combinations of docetaxel with other agents are explored as CPC mobilizing regimens for autografting.
Danova
M
M
Internal Medicine and Medical Oncology, University and IRCCS San Matteo, I-27100 Pavia, Italy.
Porta
C
C
Ferrari
S
S
Brugnatelli
S
S
Comolli
G
G
Riccardi
A
A
Ascari
E
E
D000328:Adult; D018952:Antigens, CD34 / Q000097:blood; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D000077143:Docetaxel; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D043823:Taxoids
D018952:Antigens, CD34; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; D017239:Paclitaxel