Abstract:
Objective
To compare the efficacy and safety of two neoadjuvant therapies: albuminbound paclitaxel combined with epirubicin and cyclophosphamide, and cremophor-formulated paclitaxel combined with epirubicin and cyclophosphamide in breast cancer patients.
Methods
A total of 120 breast cancer patients were enrolled and randomly divided into study group (n=60) and control group (n=60). In study group, albumin-bound paclitaxel 260 mg/m2, epirubicin 60 mg/m2 and cyclophosphamide 500 mg/m2 were administrated every 3 weeks for 4 cycles as neoadjuvant therapy; in control group, cremophor-formulated paclitaxel 175 mg/m2, epirubicin 60 mg/m2 and cyclophosphamide 500 mg/m2 were administrated every 3 weeks for 4 cycles as neoadjuvant therapy during the same time period. The pathologic complete response(pCR) rate, clinical complete remission (cCR) rate, clinical partial remission(cPR) rate, clinical response rates (cRR), safety and toxicity in the two groups were recorded. The expressions of PI3K, AKT, mTOR and BAD in tumor tissue were examined and compared before and after chemotherapy in two groups. χ2 test was used for rate comparison between groups and clinicopathological analysis. t test was used for measurement data.
Results
The patients in two groups achieved good clinical response: 28 patients (46.7%, 28/60) in study group and 11 (18.3%, 11/60) achieved cCR, the difference was statistically significant (χ2=10.978, P=0.001). The pCR rate was 16.7% (10/60) in study group, higher than 5%(3/60) in control group (χ2=4.227, P=0.040). There were no treatment-related deaths or grade 3 and 4 toxicity in both groups. The most common adverse events in study group were periphery sensory neuropathy, neutropenia, nausea and vomiting.The neutropenia occurred in 31.7% of the patients(19/60) in study group, in 51.6% of the patients(31/60)in control group(χ2=4.937, P=0.026). And sensory neuropathy occurred in 38.3% of the patients (23/60)in study group and in 18.3% of the patients (11/60) in control group during chemotherapy. All patients had normal left ventricular ejection fraction range (＞50%) before and after therapy in both groups. No drug discontinuation, drug delay, drug reduction, drug-related hypertension or postponed operation occurred during the study period. After chemotherapy, in study group, the positive rate of PI3K was decreased by 45.0%,mTOR by 43.3% and AKT by 41.7% and BAD positive rate was increased by 21.6% (all P=0.05).Compared with control group, the positive rates of PI3K,AKT and mTOR in the study group were significantly decreased (58.3% vs 28.3%,χ2=10.995, P=0.001;46.7% vs 16.7%, χ2=13.713, P=0.000, 75% vs 40%, χ2=15.038, P=0.000), but there was no difference in the positive rate of BAD between two groups(33.3% vs 48.3%, χ2 = 2.794, P = 0.095).
Conclusion
Albumin-bound paclitaxel combined with epirubicin and cyclophosphamide as neoadjuvant therapy has the advantages over cremophor-formulated paclitaxel combined with epirubicin and cyclophosphamide in breast cancer patients, including better clinical response, lower incidence of neutropenia and sensory neuropathy and decreased expression of PI3K, AKT and mTOR, which is worthy of clinical application.
Key words:
Breast neoplasms,
Neoadjuvant therapy,
Albumin-bound paclitaxel
Feng Yu, Jinjin Liu, Sheng Zhang, Xiaobei Zhang, Jin Zhang. A phase II clinical study of albumin-bound paclitaxel used in neoadjuvant therapy in breast cancer women[J]. Chinese Journal of Breast Disease(Electronic Edition), 2014, 08(04): 236-243.