A Phase II Study of Preoperative Capecitabine and Concomitant Radiation in Women with Advanced Breast Cancer
Mené sur 32 patientes atteintes d'un cancer du sein réfractaire à la chimiothérapie (durée médiane de suivi : 12,9 mois), cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse, et la toxicité d'un traitement combinant de manière concomitante capécitabine et radiothérapie
Background : We conducted a prospective phase II study to examine the response rate of gross chemo-refractory breast cancer treated with concurrent capecitabine (CAP) and radiotherapy (RT). Methods : Breast cancer patients with inoperable disease after chemotherapy, residual nodal disease after definitive surgical resection, unresectable chest wall or nodal recurrence after a prior mastectomy, or oligometastatic disease were eligible. Response by RECIST criteria was assessed after 45Gy. Conversion to operable (CTO), locoregional control, and grade>3 toxicities were assessed. The first nine patients received CAP 825 mg/m2 BID continuously. Due to toxicity, subsequent patients received CAP only on radiation days. Kaplan-Meier analysis was used to estimate overall survival (OS) and locoregional recurrence-free survival (LRFS). Results : From 2009-2012, 32 patients were accrued; 26 received protocol-specified treatment. Median follow-up was 12.9 months (interquartile range 7.1–42.9). Nineteen patients (73%) had partial or complete response. Fourteen patients (53.9%) experienced grade 3 non-dermatitis toxicity (7/9 continuous dosing). Three/four inoperable patients converted to operable. One-year actuarial OS in the treated cohort was 54%. The trial was stopped early after interim analysis suggested futility independent of response. Treatment was deemed futile (i.e., CTO but M1 disease immediately post-op) in 9/10 patients with triple-negative (TN) versus 6/16 with non-TN disease (p=0.014). Median OS and 1-yr LRFS among non-TN vs. TN patients was 22.8 vs. 5.1 months, and 63% vs. 20% (p=0.007). Conclusions : Capecitabine can be safely administered on radiation days with careful clinical monitoring and was associated with encouraging response in this chemo-refractory cohort. However, patients with TN breast cancer had poor outcomes even when response was achieved. Further study in non-TN patients may be warranted.