Eighteen RCTs (7 phase II and 11 phase III) were identified (6,205 patients).
Neoadjuvant taxane regimens versus other neoadjuvant regimens (10 trials, 3,873 patients).
Seven trials were reported in abstract form only. Of the other three, two did not report the method of randomisation and none were blinded.
Paclitaxel was associated with a statistically significant improvement in pathological complete response (25% versus 0%), but no difference in pathological partial response in one small study. Neoadjuvant paclitaxel was associated with higher rates of breast conserving therapy in 2 studies, but no information was available on whether these differences were statistically significant.
Docetaxel was associated with a significant improvement in pathological complete response in one of 3 studies (26% versus 13%, p<0.001); with improved clinical overall response in one study (85% versus 64%, p=0.001); and with higher rates of node-negative disease at surgery (58% versus 51%, p<0.001) in one study. Three studies found that neoadjuvant docetaxel was associated with higher rates of breast conservation, but the statistical significance of these findings was unclear.
One study found that neoadjuvant docetaxel was associated with better overall survival (97% versus 84%, p=0.02) and disease-free survival (93% versus 78%, p=0.04) at 38 and 65 months, respectively, whereas another 2 studies found no significant difference in disease-free survival at 32 months or in the median length of progression-free survival.
Neoadjuvant taxane regimens versus adjuvant taxane regimens (1 trial, 892 patients).
The study was reported in abstract form, thus its quality could not be determined.
Compared with those who received no neoadjuvant chemotherapy, patients who received neoadjuvant taxanes were significantly more likely to be node-negative at surgery (61% versus 38%, p=0.0001) and to have breast conservation (71% versus 35%, p<0.0001).
Taxane dose and/or schedule comparisons (7 trials, 2,492 patients).
Four trials were reported in abstract form only. The remaining trials suffered from poor reporting of the method of randomisation and the use of blinding.
Significantly higher numbers of pathological complete responses were reported for one study of 12 versus 4 cycles of neoadjuvant paclitaxel combination chemotherapy (16% versus 4%, p=0.03); for one study of weekly versus 3-weekly paclitaxel (29% versus 14%, p<0.01); for one study of six versus three cycles of epirubicin and docetaxel (19% versus 8%, p=0.0045); and for one study of dose-dense sequential docetaxel compared with standard therapy (18% versus 10%, p=0.03). Another study found higher pathological complete response in patients treated with six cycles as opposed to four cycles of doxorubicin and paclitaxel; however, the significance of these findings was not reported.
One trial reported a higher rate of breast conservation in women who received dose-dense compared with standard epirubicin and paclitaxel (66% versus 55%, p=0.016).
One trial reported higher rates of node-negative disease at surgery in women who received combination compared with sequential doxorubicin and docetaxel (53% versus 19%; 2.17 versus 4.81 positive nodes, p=0.037).
Adverse effects of taxanes.
Rates of adverse events were inconsistent and p-values were rarely reported. However, in general, haematological toxicity (neutropenia and febrile neutropenia) was more frequently associated with taxane-containing regimens. There was some evidence that neurotoxicity may be associated with neoadjuvant paclitaxel and hand-foot syndrome with neoadjuvant docetaxel. There was little evidence to suggest other adverse events were more commonly associated with neoadjuvant taxanes.