The evidence for this protocol comes from a randomised controlled trial conducted by National Surgical Adjuvant Breast and Bowel Project (NSABP) B-15.r
The trial compared 4 cycles of 3 weekly AC (doxorubicin and cyclophosphamide) with 6 cycles of 4 weekly CMF (cyclophosphamide, methotrexate and fluorouracil) in patients with breast cancer non-responsive to tamoxifen.
The study also compared the sequential use of both AC and CMF treatment to AC alone.
A total of 2194 patients were enrolled into the study. The primary end point was disease free survival (DFS) and overall survival (OS)
More recently, trials of AC alone versus AC followed by paclitaxel in similar patients show improved results with the addition of paclitaxel. Link to evidence for sequential paclitaxel.
A meta-analysis by the 2005 Early Breast Cancer Trialists' Collaborative Group (EBCTCG)r found an improved efficacy of chemotherapy regimens containing anthracyclines over those without.
Efficacy
After a median follow-up of 3 years, there was no significant difference in DFS with AC (62%) vs CMF (63%) and in OS with AC (83%) vs CMF (82%).r
AC was found to be preferable as it was completed more quickly, with less visits to health professionals, less days of chemotherapy administration and required use of less antiemetic medications.
However, AC alone is less effective than AC combined with a taxane, but AC alone is associated with less toxicity than when combined with a taxane. Link to evidence for sequential paclitaxel.
Fisher r |
AC (%) |
CMF (%) |
p-value |
Disease-free survival (DFS) |
62 |
63 |
NS |
Overall survival (OS) |
83 |
82 |
NS |
Toxicity
The following table lists the toxicities found in patients in the NSABP B-15 trial
Toxicityr |
AC (%) |
CMF (%) |
AC-CMF (%) |
Nausea with vomiting |
71 |
56 |
37 |
Nausea without vomiting |
16 |
20 |
43 |
Alopecia (complete) |
70 |
6 |
15 |
Neutropenia (grade 3 or 4) |
4 |
5 |
10 |
Diarrhoea (>4 stools/day) |
3 |
3 |
5 |
Cardiovascular toxicity (functional) |
0.4 |
0.2 |
0.1 |
Quality of life information was not collected by the above trial; however, a sub study (NSABP B23-QOL) specifically compares the differences in the quality of life between women receiving AC and CMF. This study found no overall difference in quality of life between the two treatment groups, although the two treatments do produce different symptoms. Side effects tended to occur more rapidly on AC, however as it was completed much sooner than CMF, recovery was also more rapid.r