Weekly paclitaxel seems to be superior to every-3-week paclitaxel, similar to that observed in the adjuvant setting. For example, in a preoperative trial led by investigators at MDACC, 258 patients were randomly assigned to receive a) weekly paclitaxel (either 80 mg/m
2 for 12 weeks to those with clinically node-positive disease or 150 mg/m
2 3 weeks on and 1 week off for 12 weeks to those with clinically nodepositive disease) or b) every-3-week paclitaxel (225 mg/m
2 every 3 weeks for four cycles). Both the pCR rates (28.2% vs. 15.7%;
p = .02) and breast conservation rate (47% vs. 38%;
p = .05) were higher in those who received weekly paclitaxel than those who received every-3-week paclitaxel (
20).
Conceptually, the same regimen and schedule used for adjuvant therapy could be used for preoperative therapy. Thus, as in the adjuvant setting, the administration of chemotherapy cycles every 2 weeks instead of every 3 weeks, an approach that is being referred to as
dose-dense chemotherapy, might be superior to a conventional dose regimen, though strong data from randomized clinical trials is lacking. Trials comparing dose-dense regimens to conventional regimens have had differences in the dose and regimen between the groups, making it difficult to draw clear conclusions. For example, in the AGO-1 trial (
21), eligible patients (n = 668) were randomly assigned to receive either a) dose-dense epirubin (150 mg/m
2 every 2 weeks for three cycles) followed by paclitaxel (225 mg/m
2 every 2 weeks for three cycles) or b) a conventional dose of epirubicin (90 mg/m
2 every 3 weeks for four cycles) and paclitaxel (175 mg/m
2 every 3 weeks for four cycles); the dose-dense sequential schedule was associated with higher pCR (18% vs. 10%;
p = .008) as well as improvement in DFS (HR = 0.71;
p = .011), and OS (HR = 0.83;
p = .041) as compared to the conventional combination schedule. However, it is unclear whether the superiority of the dose-dense regimen was due to the dose-dense schedule or the addition of taxanes.
Nevertheless, in the U.S., dose-dense AC (followed by paclitaxel) is commonly used in clinical practice. This involves the administration of Adriamycin 60 mg/m2 every 2 weeks along with cyclophosphamide 600 mg/m2 every 2 weeks for a total of four cycles. This should be given in conjunction with appropriate antiemetic prophylaxis and growth factor support.