Metronomic methotrexate and cyclophosphamide after carboplatin included adjuvant chemotherapy in triple negative breast cancer: a phase III study

Despite being chemosensitive, the majority of triple negative breast cancer (TNBC) patients recur. The primary study objectives were to compare disease free survival (DFS), and overall survival (OS) for TNBC after adjuvant chemotherapy, who underwent maintenance metronomic chemotherapy versus no maintenance therapy. TNBC patients were eligible for enrolment if they had TNM stages II-III and fit with our inclusion criteria. Patients were assigned to either: group 1, 3 cycles FEC-100 then 3 cycles docetaxel, carboplatin, followed by maintenance metronomic chemotherapy for 1 year; and group 2, 3 cycles FEC-100 then 3 cycles docetaxel. Between November 2008 and December 2014, 158 patients (78 group 1, and 80 group 2) were enrolled. The mean age was 46 years. The median DFS for groups 1,2 were 28 and 24 months, respectively; P value 0.05. The median OS for groups 1,2 were 37 and 29 months, respectively; P values 0.04. Additionally, during the follow-up period, the overall distant metastasis recurrence rates for groups 1,2 were 26% and 37% respectively. Finally, treatment protocol was tolerated well in both groups with mild toxicity profiles. Extended adjuvant metronomic chemotherapy achieved significant improvement in the survival and was well tolerated.