P3-14-30: Concurrent Celecoxib with FEC Followed by Docetaxel Shows Good Responses and Prognosis in a Neoadjuvant Breast Cancer Study.
Authors: Chow LWC , Tung SY , Ng T-Y , Oh D-Y , Im S-A , Lee M-H , Yip AYS , Toi M , Glück S 
Published: June 2012

BACKGROUND: Anthracycline and taxane have been widely used as neo-adjuvant therapy(NAT) for breast cancer. Addition of COX-2 inhibitors might enhance the anti-cancer effect of chemotherapy. This prospective clinical trial studied 5-fluorouracil/Epirubicin/Cyclophosphamide-Docetaxel(FEC-T) with concurrent celecoxib(CXB) as NAT for breast cancer patients(pts). Primary endpoints were pathologic complete response(pCR) and clinical response(CR), secondary endpoints were safety and breast conservative therapy(BCT) rate. Disease-free survival(DFS) was also determined.

METHODS: This study accrued 91 pts among which 87 pts received FEC(F:500mg/m2; E:100mg/m2; C:500mg/m2) followed by T(100mg/m2). In the initial phase, the study randomized 12 and 11 pts to receive 4 cycles of FEC followed by 4 cycles of T with or without concurrent CXB(400mg bid) respectively. Due to possible cardiovascular events from COX-2 inhibitors, the study protocol was revised to a single arm phase II study which recruited another 64 pts who received FEC-T with concurrent CXB at reduced dosage(200mg bid). Primary endpoints were compared between pts with and without CXB using Fisher's Exact test. All endpoints and survival were evaluated for phase II subjects.

RESULTS: Out of 87 pts, 84 invasive breast cancer pts, age ranged 30–62 (mean: 46±6 years) and clinically staged IIA (n=48,57.1%), IIB (n=28,33.3%) and IIIA (n=8,9.5%), are eligible for comparison between groups (CXB+,n=73 / CXB-,n=11). More CRs were observed in CXB+ than in CXB- (94.5% vs. 72.7%, p=0.044) but pCR did not show statistical difference. In the phase II study, 57/64 pts, including luminal A 35(61.4%), luminal B 12(21.1%), HER-2 positive 8(14.0%), and triple negative (TPN) 2(3.5%), completed NAT and definitive surgery. pCR plus near pCR was observed in 18(31.6%)pts. Excluding TPN subtype, pCR (p=0.761) did not but near pCR (p=0.043) differ among subtypes. Those with HER-2 amplification had higher near pCR than those who did not (6/20 vs. 3/37, p=0.031). Out of 56 pts evaluable for CR, 43(75.4%) and 13(22.8%) pts achieved complete and partial CR respectively. Over 80% pts received BCT after NAT and that 11/14(78.6%) pts who initially were unsuitable for BCT with a baseline tumor &gt;5cm became eligible after NAT. At a median follow-up of 37 months, 61 pts who completed ≥6 cycles of NAT and surgery were followed and 80% of pts are still disease-free. Pts responding to the NAT has fewer chance of relapse (p=0.03). Neither life-threatening toxicity nor cardiotoxicity was observed. The most commonly observed grade 3/4 adverse events included neutropenia and leucopenia: 39.1% and 20.3% during FEC, and 16.1% and 12.9% during T respectively. Febrile neutropenia was observed in 9.4% pts during FEC, but none during T. Less than 40% of pts required G-CSF support. Other mild toxicities were manageable.

CONCLUSIONS: Higher CR was observed in pts receiving neo-adjuvant FEC-T with concurrent CXB which appeared well-tolerated and safe. Rate of BCT is high after the treatment. Pts with HER-2 amplified breast cancer responded better than those who did not. Chance of relapse is significantly reduced for NAT responders. Further investigation of using COX-2 inhibitors with neo-adjuvant chemotherapy is warranted.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-30.