Neoadjuvant chemotherapy with metronomic doxorubicin, cyclophosphamide, and capecitabine in patients with locally advanced (LA) triple-negative breast cancer (TNBC).

Abstract

e12027 Background: TNBC is associated with aggressive behavior and poor prognosis. It has been shown that patients (pts) with TNBC with pathological complete regression (pCR) after neoadjuvant chemotherapy have a higher survival. Rates of pCR with standard antracycline- and taxanebased chemotherapy regimens don’t exceed 20-27%. Dose-dense and metronomic schedules may be more effective in these highly proliferative tumors. We performed a prospective pilot trial to evaluate efficacy of metronomic schedule of doxorubicin, cyclophosphamide and capecitabine in pts with LA TNBC. Methods: Pts with LA TNBC (cT2-4N1-3M0) were treated with doxorubicin 25 mg/m2 iv weekly, cyclophosphamide 50 mg po daily and capecitabine 1500 mg po daily for planned 16-19 weeks followed by surgery. Pathological response was evaluated according to the Chevallier classification. Results: Twenty pts was included in the study in 2009-2010. Median agewas 47 years (33-70), 63% of pts had tumor grade 3, Ki67 was >20% in all cases. Nineteen pts completed chemotherapy (median treatment duration 17.1 weeks) and underwent surgery. One pt had a disease progression during chemotherapy and was switched to 2nd-line chemotherapy. Seven pts (36,8%) achieved a pCR (6 pts class 1 and 1 pt class 2). With median follow-up of 33 months, 3-year DFS and OS were 60%. All but one pt with pCR, who developed brain mts shortly after surgery, are currently alive without relapse. In contrast 50% of pts with residual tumor relapsed. Pts with pCR had significantly higher median cumulative dose of doxorubicin (420 mg/m2) than pts with residual disease (300 mg/m2, p=0.046). The dose-limiting toxicities were hand-foot syndrome (26.3% grade 3), mucositis (31.6% grade 3), and neutropenia (31.6% grade 3-4), which resulted in permanent discontinuation of doxorubicin in 4 pts. Conclusions: Despiterelatively hightoxicity metronomic doxorubicin, cyclophosphamide and capecitabine regimen shows promising activity as neoadjuvant treatment of LA TNBC. Achievement of pCR and higher cumulative dose of doxorubicin were strongly associated with improvement of survival.

Molecular Magnetic Resonance Imaging of Tumor Response to Therapy

“…2a ). Doxorubicin dose was selected to approximate clinical metronomic chemotherapeutic doses 20 , and the radiation treatment mimics a single fractionated dose received during current stereotactic ablative radiotherapy treatment regimens employed in the clinic 21 . Both the metronomic chemotherapy and the radiation therapy resulted in a substantial tumor growth delay relative to the untreated controls ( Fig.…”