Concurrent Neoadjuvant Chemotherapy and Radiotherapy in Locally Advanced Breast Cancer
Mené sur 27 patientes atteintes d'un cancer du sein de stade localement avancé et sur 81 témoins, cet essai de phase II évalue, du point de vue de la réponse pathologique complète, l'intérêt d'ajouter de manière concomitante une radiothérapie à une chimiothérapie néo-adjuvante par fluorouracile-épirubicine-cyclophosphamide-docétaxel
Purpose : Locally advanced breast cancer (LABC) patients have poor overall survival. We evaluated whether concurrent neoadjuvant radiation added to standard chemotherapy could increase the pathological complete response (pCR) to treatment. Methods and Materials : This prospective phase-II trial recruited thirty-two LABC patients from 2009-2011. Patients received neoadjuvant q3 weekly 5-fluorouracil (500mg/m2), epirubicin (100mg/m2) and cyclophosphamide (500mg/m2) for 3 cycles, followed by weekly docetaxel (35mg/m2) for 9 cycles. Regional radiation (45Gy/25 plus 5.4Gy/5) was delivered concurrently with docetaxel, then modified radical mastectomy. Patients were matched post-hoc by a blinded statistician to a concurrent cohort treated with neoadjuvant chemotherapy, modified radical mastectomy and adjuvant regional radiation. Results : Thirty of 32 patients completed treatment. Twenty-seven were successfully matched by propensity score to 81 control patients by age, stage and molecular subtype. The concurrent chemoradiation produced a significant increase in pCR (14% vs 22%, p<0.001), but no statistically significant difference in disease-free and overall survival at 3 years (69% vs 81%, p=0.186; Hazard Ratio 0.51; 74% vs 89%, p=0.162; Hazard Ratio 0.46). Toxicity included 25% of patients with grade 3 pneumonitis and 25% of patients with dermatitis, and one death. Conclusions : Concurrent neoadjuvant radiation added to radiosensitizing chemotherapy significantly improved pCR. A prospective randomized clinical trial is warranted to exploit the improved response seen with concurrent therapy but using another radio sensitizing taxane in order to better minimize treatment related toxicity and determine its impact on overall survival.