Phase II study of neoadjuvant paclitaxel and cisplatin for operable and locally advanced breast cancer: analysis of 126 patients

Abstract

In an earlier study, we have demonstrated a high clinical and pathologic response rate of neoadjuvant paclitaxel (P) and cisplatin (C) for patients with locally advanced breast cancer (LABC). The current phase II study includes larger number of patients who had longer follow-up. A total of 126 consecutive patients with noninflammatory LABC (T2 44 cm, T3 or T4, N0 -N3, M0) were included in the study. Patients were scheduled to receive three to four cycles of the neoadjuvant PC (paclitaxel 135 mg m À2 and cisplatin 75 mg m À2 on day 1) every 21 days. Patients were then subjected to surgery and subsequently received six cycles of FAC (5-fluorouracil 500 mg m À2 , doxorubicin 50 mg m À2 , and cyclophosphamide 500 mg m À2 ) or four cycles of AC (doxorubicin 60 mg m À2and cyclophosphamide 600 mg m À2 ); all drugs were administered intravenously on day 1 with cycles repeated every 21 days. Patients then received radiation therapy, and those with hormone receptor-positive tumours were given adjuvant tamoxifen intended for 5 years. The median age was 41 years. Clinically, 12, 52, and 37% of patients had T2 44 cm, T3, and T4, respectively. The mean tumour size was 7 cm (95% CI, 7.3 -8.5). The clinical nodal status was N0, N1, and N2 -N3 in 32, 52, and 17% of patients, respectively. Disease stage at diagnosis was IIA (2%), IIB (32%), IIIA (28%), and IIIB (39%). Clinical assessment of the primary tumour and the axillary nodal status after primary chemotherapy showed that 35 patients (28%) achieved complete response (cCR), while 80 (63%) demonstrated partial response to PC. Of patients with evaluable pathologic data of the primary tumour (123 patients), complete pathologic response (pCR) was achieved in 29 patients (24%), and an additional nine (7%) only had a microinvasive disease. Moreover, 20 of the 122 patients (16%) had no residual disease in the primary tumour or in the axillary nodes. Failure to attain cCR predicted failure to achieve pCR. At a median follow-up of 37.5 months (95% CI, 31.5 -43.3), 71% were alive with no recurrence, 16% were alive with evidence of disease, and 13% were dead. Of the 122 patients who had surgery, 36 (29%) developed recurrence including one of the patients who attained pCR. The median overall or disease-free survival has not been reached with a projected 5-year overall survival (OS) and disease-free survival (DFS) of 85% (74%) and 63% (75%), respectively. On multivariate analysis, clinical response of the primary tumour, pathological response of the primary tumour, and the pathological nodal status were identified as independent prognostic variables for DFS. No variable, however, was identified to prognosticate OS. PC was acceptably safe. Neoadjuvant PC as used in this phase II study in a multidisciplinary strategy was highly effective. Clinical and pathologic responses remain the most important variables that predict outcome.

Weekly cisplatin, epirubicin, and paclitaxel with granulocyte colony-stimulating factor support vs triweekly epirubicin and paclitaxel in locally advanced breast cancer: final analysis of a sicog phase III study

“…Several cisplatin-based regimens have been tested in the neo-adjuvant setting, showing high anti tumour activity (Orlando et al, 2001;Ezzat et al, 2004). In the mid-nineties, we started the assessment of a weekly triplet regimen including cisplatin, epirubicin, and paclitaxel (PET regimen) in breast cancer patients (Frasci et al, 1999).…”

A phase II study of neoadjuvant chemotherapy with docetaxel, cisplatin and trastuzumab for T2 breast cancers

“…Clinical and pathological responses may remain the most important variables in predicting breast cancer outcome after chemotherapy. Furthermore, patients experiencing a pathologic complete response (pCR) have a statistically signiWcant survival beneWt [1,2]. Liedtke [1] reported that triple-negative breast cancer with a pCR has excellent survival.…”

“…Preclinical data indicate that the combination of docetaxel, cisplatin and trastuzumab (TCH) may have the potential for clinically signiWcant activity against breast cancers that overexpress the her2/neu gene (HER2) [1][2][3]. The potential advantage of neoadjuvant chemotherapy is in the ability to assess the response rate in vivo and in downstaging the primary tumor and regional lymphatic metastases, which improves the cosmetic result.…”

“…Liedtke [1] reported that triple-negative breast cancer with a pCR has excellent survival. Ezzat demonstrated a high clinical and pathological response rate (24%) for paclitaxel and cisplatin in patients with locally advanced breast cancer and concluded that adjuvant paclitaxel and cisplatin in a multidisciplinary strategy were highly eVective [2].…”

Prospective phase II study of neoadjuvant doxorubicin followed by cisplatin/docetaxel in locally advanced breast cancer

“…We started studying platinumbased regimens in 1995, and have demonstrated the significant efficacy of the combination of paclitaxel and cisplatin in the management of patients with metastatic breast cancer [20]. In an earlier phase II paclitaxel and cisplatin utilized in patients with LABC, the regime was very effective with reasonable toxicities and high pathologic complete response rate [21,22].…”