Study To Evaluate the Efficacy and Safety of Zoladex Combined with CEF Chemotherapy as Neo-Adjuvant Therapy in Hormone Responsive, Premenopausal, Operable Breast Cancer Patients.

Abstract

Abstract Purpose: To evaluate the efficacy and safety of Zoladex combined with CEF chemotherapy as neo-adjuvant therapy in hormone responsive, premenopausal, operable breast cancer patients.Patients and Methods: 119 patients with hormone responsive, premenopausal, operable breast cancer have been enrolled. Zoladex 3.6 mg was administered by subcutaneous injection per 4 weeks for 3 cycles, concurrently, CEF (CTX 600mg/m2, EPI 60-90 mg/m2, 5-Fu 500 mg/m2) were given per 3 weeks for 4 cycles as neo-adjuvant therapy. The primary objective was pathological complete response (PCR) rate in the breast. The secondary objectives included clinical complete response (CR) rate, clinical partial response (PR) rate, clinical overall response rate (ORR), safety and toxicity, change of biological marker status (ER, PR, HER-2) pre- and post-therapy.Results: 31 patients (26.1%) achieved clinical complete response and 76 patients (63.9%) achieved clinical partial response; the overall clinical response rate was 90.0%. 14 patients (11.8%) achieved pathologic complete response to T0/Tis, N0 and 20 patients (16.8%) achieved pathologic complete response to T0/Tis, Nx. When stratified by the clinical lymph-node status, the clinical partial response rate in clinical lymph-node negative group was significantly better than clinical lymph-node positive group (p=0.02). When stratified by the hormonal status, the clinical partial response rate in ER+PR+ group was significantly better than ER+PR- and ER-PR+ group (p=0.0471). There was no significant difference between HER-2+ group and HER-2- group when stratified by the HER-2 status. There was no treatment-related death and no grade 3 or grade 4 toxicity. The common adverse events were nausea (grade1 65.5%, grade2 18.5%), vomiting (grade1 58.8%, grade2 13.4%), alopecia (grade1 45.4%, grade2 54.6%). Other adverse events with more than 5% incidence included neutropenia (grade1 5.0%) and hepatic dysfunction (grade1 9.2%). There was no drug discontinuation and no drug delay or dose reduction occurred. Hormonal receptor became negative post-therapy in 11 patients' (9.2%), which clinical response rate significantly lower compared with post-therapy hormonal receptor positive group (p<0.001). The change of HER-2 status had no relationship with clinical efficacy. 109(91.6%) patients achieved amenorrhea after the first cycle of Zoladex, 10(8.4%) patients achieved amenorrhea after the second cycle of Zoladex. Mean period of amenorrhea was 6 months (4–17 months). 43 patients have been followed up for more than 1 year after operation and among them 6(14.0%) patients still remain amenorrhea.Conclusion: Zoladex combined with CEF chemotherapy as neo-adjuvant therapy in hormone responsive, premenopausal breast cancer patients was more effective and had no more toxicity than CEF chemotherapy alone. This regimen was most effective especially in the clinical lymph-node negative group and ER/PR double positive group. The clinical response rate will be lower if the hormonal receptor became negative after therapy. The efficacy of this regimen has no relationship with HER-2 status. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4087.