P3-14-15: Non-Randomized, Open Label Phase II Trial Evaluating the Safety and Efficacy of Taxotere (T) Followed by Myocet (M) + Cyclophosphamide (C) as First-Line Treatment for HER2−Negative Breast Cancer (BC).
Authors: García-Mata J , Calvo L , López R , Ramos M , Castellanos J , Heras L 
Published: June 2012

Abstract
Background
Breast cancer is the most common malignancy in females in Europe and is the most common cause of cancer mortality in women, with doxorubicin playing an important role in chemotherapy (CT) regimens used in this setting but limited by cardiotoxicity. Liposomal encapsulated doxorubicin was designed to minimize healthy tissue distribution by altering pharmacokinetics thus reducing cardiotoxicity while preserving antitumor efficacy. The current study was developed to assess the pathologic complete response (pCR), response rate and safety of treatment with taxotere (T), non-pegylated liposomal doxorubicin (M) and cyclophosphamide (C) in previously untreated patients with BC.
Methods: Patients (pts) with HER2−negative BC receiving 1st-line CT were eligible. On Day 1 of each 21-day cycle for a total of 4 cycles, pts received T 75 mg/m2 IV, followed sequentially by M 60 mg/m2 and C 600 mg/m2 IV every 3 wks for 4 cycles. Breast conserving surgery (BCS) was considered if the response was deemed satisfactory, otherwise mastectomy was performed and pCR was evaluated. Pts must have had LVEF ≥50% at the time of enrolment and had regular cardiac evaluation throughout the study (MUGA or ECHO).
Results: A total of 74 pts (50 stages II and 24 IIIA) over a 30-month period in six centres were accrued with clinical/pathological responses available for 51. The median age was 46 yrs (range 23–75). Histology: lobular 7/ductal 67. Grade I/II/III: 6/27/30. ER+/PR+: 43; ER+/ PR-: 13. Triple negative: 18. 50 pts had pre-op CT cycles and were subjected to surgery. No clinically significant change in LVEF was noticed (Pre-CT LVEF 68.5% [CI95%: 66.7−70.4]; post-CT LVEF 68.9% [CI95%: 66.0−71.7]).
On an intention to treat analysis, an objective clinical response was observed for 38 pts: 6 complete (12%) and 32 partial (63 %). In addition, 12 pts (23%) demonstrated stable disease and only one progressed (2%).The proportion of patients requiring mastectomy and BCS were 14 (28%) and 36 (72%), respectively. On 33 pts with an axillary dissection, 25 (76%) had involved nodes. After pathological review, 18/50 pts (36 %) were devoid of any tumor cells in both breast and lymph nodes according to Miller & Payne's classification. Median number of positive lymph nodes following CT was 3 (IQR 2–6). All patients were included for toxicity assessment. Grade 3–4 neutropenia and febrile neutropenia was seen in 23% and 10% pts, respectively. Principal non-hematologic grade 3–4 toxicities included allergic reaction/hypersensitivity in 6% pts, and asthenia, diarrhoea and vomiting in 1%. No pts developed symptomatic CHF. Ten pts discontinued treatment: 5 due to taxane-hypersensitivity reaction, 3 due to disease progression and 2 due to protocol violation.
Conclusions: This multi-centre phase II trial clearly demonstrates significant activity (pCR 36%) for neoadjuvant taxane sequentially followed by non-pegylated liposomal doxorubicin and cyclophosphamide regimen in a HER-2 negative BC population. Overall the treatment regimen was well tolerated. Sequential T→MC is safe and not associated with changes in LVEF. An updated evaluation of efficacy and toxicity profile analysis will be presented.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-15.