Page 191 - Read Online

Page 4 of 8 Elzaafarany et al. J Cancer Metastasis Treat 2018;4:14 I http://dx.doi.org/10.20517/2394-4722.2017.55

= 0.007). There was no significant OS benefit from adding taxanes to anthracycline according to NSABP-B28
trial. It is noted that only 75% of the patients in the AC-T arm completed the full AC-T course, and this
could be the reason for the absence of OS benefit. It is important to remember that there were 7 deaths which
could be attributed to chemotherapy in the AC-T arm. However, it was recorded that only 3% of the patients
[7]
in the AC-T arm developed febrile neutropenia, and 18% had grade III neurotoxicity in the same arm .

GEICAM-9906 trial
The Spanish Breast Cancer Research Group published its special trial GEICAM-9906 in 2008, and it used
weekly paclitaxel regimen, however it used only 8 weeks of paclitaxel instead of 12 weeks. It randomized 1246
node positive patients to two arms; the first one received 6 cycles adjuvant FEC and the second arm received
2
3 cycles adjuvant FEC followed by 8 cycles of weekly paclitaxel 100 mg/m (FEC-P). There was a statistically
significant difference in DFS from adding weekly paclitaxel to FEC when compared to adjuvant FEC alone,
as 5-year DFS was 78.5% in FEC-P compared to 72.1% (P = 0.006). But, this benefit was accompanied by
increase in NF of 9.5% vs. 5.1%. DFS benefit depended on the number of positive LNs and tumor size, also it
was better with HER2 negative patients and patients with ER negative tumors based on subgroup analyses of
[8]
this trial .
GEICAM-9805 trial
Another Spanish trial (GEICAM-9805) was published in 2010 which investigated the benefit of adding
adjuvant taxanes in node-negative breast cancer patients, and its arms were identical to the BCIRG-001 arms.
But, unlike the BCIRG trial it allowed primary G-CSF prophylaxis in its TAC arm which greatly declined the
rate of NF in contrast to the BCIRG study where the NF risk was high. Interestingly, it showed a significant
DFS benefit in node-negative patients. In this study, 1060 node-negative patients were randomized to receive
6 cycles adjuvant FAC vs. 6 cycles adjuvant TAC. The results showed that the 5-year DFS was 90.1% in TAC
arm compared to 85.3% in the FAC arm (P = 0.03). NF occurred in 9.6% with TAC vs. 2.3% in the FAC arm
(P ≤ 0.001). It is important to note that the overall grade 3-4 toxicity from TAC was significantly higher than
[9]
those with FAC (28.2% vs. 17%; P < 0.001) .

RANDOMIZED TRIALS WHICH DID NOT SHOW BENEFIT FROM ADDING TAXANES
Intergroup trial E-2197
One of the negative taxanes’ trials is the North American Breast Cancer Intergroup Trial (E 2197) that was
published in 2008 and compared 4 cycles adjuvant AC to 4 cycles adjuvant concurrent doxorubicin-docetaxel
2
(60 mg/m ) AT-arm. It included 2882 high-risk negative nodes breast cancer patients and those with 1-3
positive nodes. Also, primary G-CSF prophylaxis was not allowed in this trial. The results showed that 5-year
DFS was 85% in both arms of the study (P = 0.78), however in subgroup analyses there was a trend of better
DFS in patients with ER/progesterone receptor (PR) negative (P = 0.02) and those with ER positive/PR
negative (P < 0.01). Grade 3 neutropenia was 26% in AT arm vs. 10% in AC arm (P < 0.05). There are some
explanations why this trial was negative; one of those possible reasons is that the negative nodes patients
2
constituted 66% of the study population. Secondly, the lower dose of docetaxel which was 60 mg/m . Lastly,
[10]
the short overall taxanes course as it was only 4 cycles of AT .
TACT trial
The UK-TACT trial, published in 2009, is another example of negative taxanes’ trials which did not show
a statistically significant benefit of adding taxanes to anthracyclines in adjuvant treatment of breast cancer,
and there are two possible explanations for this negative result. The first one is that it included both node
positive and node negative patients whereas the most of positive taxanes trials included only patients with
positive LNs. The second reason is that the control arm received a long course which is 8 cycles of either FEC
regimen or 4 cycles FEC followed by another 4 cycles of CMF, in contrast to both the NSABP and BCIRG
[11]
trials in which the control arm received only 4 cycles of AC and 6 cycles of FAC respectively . Another
negative trial was MA-21 trial from Canada, which also included node negative patients and the control arm