Neoadjuvant docetaxel for operable breast cancer induces a high pathological response and breast-conservation rate

Abstract

Docetaxel (Taxotere s ), alone or in combination with other anticancer agents, has proven efficacy in the first-and second-line treatment of metastatic breast cancer. This phase II study investigated the efficacy and tolerability of docetaxel as neoadjuvant chemotherapy in women with stage II -III primary operable breast cancer. Patients (n ¼ 88) were treated with six cycles of docetaxel at 100 mg m À2 every 21 days, followed by definitive surgery and radiotherapy. After six cycles of docetaxel, the overall clinical response rate was 68.4% (CI 95%: 58.1 -78.7%), including 19.0% complete remissions. Breast conservation was achieved in 72.4% of patients. A high pathological complete response (pCR) rate in breast was confirmed in 15 patients (19.8% (CI 95%: 10.8 -28.8%)) on Chevallier's classification restricted to breast and in 27 patients (35.5% (CI 95%: 24.7 -46.3%)) on Sataloff's classification. After a median follow-up of 30.8 months, 19 recurrences were documented with a median time to first recurrence of 17.3 months. Patients with stage III tumours had more recurrences than patients with stage II tumours (P ¼ 0.02). The principal toxicity of docetaxel is myelosuppression and 70.5% of patients developed grade III or IV neutropenia with 13.6% developing neutropenic sepsis. There was no case of severe cardiac toxicity, thrombocytopenia or any other serious adverse events. In conclusion, neoadjuvant docetaxel induces a high pCR and breast-conservation rate. Docetaxel monotherapy is a highly effective regimen that merits formal comparison with currently used combination regimens in a randomised phase III study.

Pathological and Clinical Response of a Primary Chemotherapy Regimen Combining Vinorelbine, Epirubicin, and Paclitaxel as Neoadjuvant Treatment in Patients with Operable Breast Cancer

“…The pCR, according to Chevallier, was comparable with the rate obtained with the NEM protocol (14%) [7] and was lower than the expected 20%, but the difference between these two values was not significant (p = 0.35). However, these results are lower than those obtained with the Taxobel protocol [10]: 19.8% and 35.5% according to the Chevallier and Sataloff classifications, respectively. Moreover, our results according to the Chevallier classification agree with the prospective phase III randomized trial of Green et al [16].…”

“…Grade 3/4 neutropenia was observed in 30% of patients, which is the same as in the NEM protocol [7]. However, this is much lower than in Taxobel [10], which reported grade 3/4 neutropenia in 70.5% of patients. Eight patients (16%) developed febrile aplasia, and grade 3 anemia was also recorded in six patients (12%).…”

“…The clinical CR (26%) was no better than and sometimes inferior to the results obtained with TNCF (51%) [8], Taxobel (36%) [10], AVCF (27%) [17], and NEM (28%) [7] protocols. Besides, there were 48% fewer clinical CRs for [10], AVCF (69%) [17], and TNCF (71%) [8] protocols, but it was lower than in the NEM protocol (87%) [7]. Moreover, as it is reported by Newman et al [19], patients with lobular carcinomas are less likely to become candidates for breast-conserving therapy after neoadjuvant chemotherapy.…”

“…The surgical margins were involved for four patients and led to a secondary mastectomy. At surgery, the median number of nodes collected was 12 (range, 3-28) and the median number of involved nodes was 2 (range, [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Among 43 patients who underwent axillary dissection, 19 (44%) were N0, 17 (40%) were N1-3, 4 (9%) were N4-9, and 3 (7%) were N≥10.…”

“…Next, a more intensive regimen was proposed: the TNCF protocol (theprubicin, vinorelbine, cyclophosphamide, 5-fluorouracil; OR = 79.7% and pCR = 33.3%) [8]. Later, with the arrival of the taxanes, which present a high response rate (OR = 40%-60%) in metastatic breast carcinoma [9] that is equal to or better than anthracyclines, the Taxobel protocol, with docetaxel alone was started (OR = 70.8% and pCR = 19.8%) [10]. The VEP protocol, based on NEM, was started a year later, with methotrexate replaced by paclitaxel.…”