The evidence supporting this protocol is provided by the NSABP B-27 trial, which was a phase III multicentre trial designed to determine the effect of adding docetaxel (T) to preoperative doxorubicin and cyclophosphamide (AC) on breast cancer response rates and disease-free survival (DFS) and overall survival (OS).r
Between December 1995 and December 2000, 2411 patients were randomly assigned to receive preoperative AC followed by surgery (n=784), AC followed by T and surgery (n=783), or AC followed by surgery then T (n=777) in patients with operable breast cancer.r
AC: Doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 21 days for 4 cycles
T: Docetaxel 100 mg/m2 every 21 days for 4 cycles
All patients received tamoxifen 20 mg/day for 5 years on the first day of chemotherapy regardless of hormone receptor status and this may have limited the impact of adding docetaxel.
The primary end points were OS, DFS, and relapse-free interval (RFI).r
Efficacy
After a median follow up of 8.5 years, 86% of the patients in the two groups assigned to receive preoperative AC only (groups 1 and 3) achieved a clinical response compared with 91% of patients in the preoperative AC and T group (P<0.001). The cCR rate was increased from 40% to 63% with the addition of four cycles of docetaxel (P<0.001). The pCR rate was increased from 13% in groups 1 and 3 to 26% in group 2 (P<0.001).r
Although there were trends toward improved DFS with addition of T, this was not significant nor was there a significant effect on OS.
(D) Overall survival (OS), (E) Disease-free survival (DFS), (F) Relapse-free interval, in NSABP B-27 trial r
© Journal of Clinical Oncology 2008
Toxicity
81% of patients completed docetaxel therapy to the planned schedule. The improved responses achieved with docetaxel were at the expense of some increased toxicity. Grade 4 toxicity was observed in 10% of patients during treatment with AC and 23% of patients during administration of docetaxel. Febrile neutropenia occurred in 21% of patients receiving docetaxel versus 7% of those receiving AC alone. However, no significant increase in neutropenic infection was observed with docetaxel usage. Non-haematological toxicities were generally mild in both groups (<1% grade 4).r
The following toxicity table is adapted from the phase II GeparDUO trial.r
Toxicity (n=176) r |
Grade 3/4 (%) |
Anaemia |
4.5* |
Neutropenia |
69.3** |
Thrombocytopenia |
2.8 |
Alopecia |
93.8 |
Fluid retention |
0 |
Infection |
1.1 |
Nausea/vomiting |
15.3*** |
Sensory and/or motor neuropathy |
7.4 |
Fatigue |
26.7 |
Skin and/or nail disorders |
10.8 |
Percentages are based on the number of evaluable patients which varied as noted: *n=178, **n=166, ***n=177