| Breast cancer is the most common disease among women, and its morbidity is going up increasingly. Chemotherapy plays an important role in the treatment, either adjuvant or rescue setting, of this disease. The taxenes, including paclitaxel and docetaxel, are both highly active agents against breast cancer. By binding to the subunit of tubulin, paclitaxel and docetaxel can stabilize and promote the reorganization of the microtubules in tumor cell, making it accumulated in G2/M phase and ultimately cause cell death. Objective To evaluate the relationship of dose intensity and the efficacy and toxicity of taxanes as a single agent in advanced breast cancer (ABC) ; to compare the efficacy and toxicity of paclitaxel and docetaxel in the treatment of ABC; to investigate the feasibility and toxicity of taxanes used in combination with other agents in these patients ; to assess the predictive role of molecular bio-markers for the clinical sensitivity of taxanes in metastatic breast cancer (MBC) . Methods In this study, there were in total 270 courses of taxanes were administered in 220 cases of advanced breast cancer patients, of which 71 courses were paclitaxel used as a single agent, and 33 courses were docetaxel alone, 110 courses of paclitaxel were administered in combination with other agents, and 56 courses were docetaxel combinations; also, in 268 courses of the taxanes treated patients, such molecular biomarkers as estrogen receptors (ER), progesterone receptors (PR), HER-2 protein, p53, MDR-1, BCL-2, were detected by immunohistochemistry (IHC) assay. Results (1) As a single agent, the response rates of paclitaxel was 41. 8%, the response rate of this agent in soft tissue metastatic patients was 38. 0%, it is highly effective in lung metastatic patients with a RR of 52. 0%, whereas the was only 7. 7% in liver metastatic patients; The relative dose intensity in the whole group is among 0.57-1.2, according to the relative dose intensityof paclitaxel used, all the patients were grouped into three categories (1, 0. 9, < 0.9 ), and the response rates in these three groups were 44. 2%, 47. 6%, 0, respectively, the differences were significant. However, there were no statistic significances in the Ⅲ -grade of hematological toxicities in these three group of patients. (2) The RR of docetaxel as single agent was 25%, the RR of this drug in lung- and live-metastatic patients were 60.0% and 27.8%, respectively. This drug was administered as either one- week or 3-week protocol. Although the efficacy was similar in these two protocol, the Ⅲ- Ⅳ grade of hematological toxicity was relatively high in later protocol . Toxicity was lower and tolerable in the one week protocol. (3) When used in combination with anthracylines, the RRs of paclitaxel and docetaxel were 38.1% and 46.2%, respectively, while combined with platins, the RRs of the two drugs were38. 3% and 33. 3%, respectively. The response rates of these two drugs, when used in combination with gemcitabine, were 42.9% and 55.6%, respectively. Ⅳ grade of neutropenia in docetaxel alone arm was 38. 5%, and 1. 2% in paclitaxel alone arm. However, when used in combination with anthracylines, FV grade of neutropenia of were 92. 3%, 47. 6%, respectively; when used in combination with gemcitabine, Ⅳ grade of neutropenia of the two drugs were28. 8% and 15. 6%, respectively ;when used in combination with platins, Ⅳ grade of neutropenia of the two drugs were57. 9% and 6. 5%, respectively. (4) In univariate analysis, The RR in ER positive arm and ER negative arm were 33. 3%, and 48. 5%, respectively (p=0. 018). While considering the HER-2 status, the RR in overexpression arm and lower-expression arm were 55. 7%, and 33. 3%, respectively (p=0. 0004) , the differences are all significant. In ER negative arm, HER-2 overexpression arm and ER positive arm, HER-2 lower-expression arm, the RR were 65. 7%, and 33. 7%, the difference was also significant (p=0. 001). As for PR, MDR-1, P53 and BCL-2, there were no statistic significances. Multivariate analysis showed that overex... |
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