Phase II Study With Epirubicin, Cisplatin, and Infusional Fluorouracil Followed by Weekly Paclitaxel With Metronomic Cyclophosphamide as a Preoperative Treatment of Triple-Negative Breast Cancer.
BACKGROUND
The aggressive biological behavior and the lack of target therapy prompts the search for new therapeutic approaches for triple-negative breast cancers.


METHODS
We evaluated the efficacy in terms of Ki-67 variation and clinical response but also the toxicity of a neoadjuvant regimen based on metronomic principles including ECF (epidoxorubicin with cisplatin on day 1 with low-dose 5-fluorouracil in continuous infusion every 21 days for 4 courses) followed by paclitaxel (90 mg/m(2)) on day 1, 8, and 15 every 28 days for 3 courses in combination with metronomic oral cyclophosphamide 50 mg/d for 12 weeks in patients with HER2-negative breast cancer (T2-T4a-d, N0-3, M0) with estrogen receptor and progesterone receptor < 10%.


RESULTS
We enrolled 34 patients from June 2009 to May 2013. All were considered evaluable on an intention-to treat basis. The mean difference between the percentage of Ki-67 positive cells evaluated in surgical resection specimens and in pretreatment tumor core biopsy was 41% (95% confidence interval [CI], 30-51; P < .0001) for the entire population, and 22% (95% CI, 7-38; P = .0097) in patients who did not achieve pathological complete response (pCR). Responses to the treatment were obtained in 31 patients [91%] of the patients, and 19 patients (56%; 95% CI, 35-70) had a pCR. Stable disease was observed in 3 patients and none had progressive disease. Grade ≥ 3 hematologic adverse events included leukopenia in 9% (3 of 34), neutropenia in 38% (13 of 34), and anemia in 3% (1 of 34) of patients. Nonhematologic Grade ≥ 3 toxicities included only stomatitis in 1 patient.


CONCLUSIONS
A neoadjuvant program with an ECF regimen followed by weekly paclitaxel with metronomic cyclophosphamide proved to be very effective, with high pCR rates, reduction of Ki-67, and it was associated with a low toxicity profile.
Division of Medical Senology, European Institute of Oncology, Milan, Italy. Electronic address: giuseppe.cancello@ieo.it.
Giuseppe
G
Cancello
Division of Epidemiology and Biostatistics, European Institute of Oncology, and Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy.
Vincenzo
V
Bagnardi
Division of Medical Senology, European Institute of Oncology, Milan, Italy.
Claudia
C
Sangalli
Division of Medical Senology, European Institute of Oncology, Milan, Italy.
Emilia
E
Montagna
Division of Medical Senology, European Institute of Oncology, Milan, Italy.
Silvia
S
Dellapasqua
Division of Medical Senology, European Institute of Oncology, Milan, Italy.
Andrea
A
Sporchia
Division of Medical Senology, European Institute of Oncology, Milan, Italy.
Monica
M
Iorfida
Department of Pathology, European Institute of Oncology, Milan, Italy; University of Milan School of Medicine, Milan, Italy.
Giuseppe
G
Viale
Department of Pathology, European Institute of Oncology, Milan, Italy.
Massimo
M
Barberis
University of Milan School of Medicine, Milan, Italy; Division of Senology, European Institute of Oncology, Milan, Italy.
Paolo
P
Veronesi
Division of Senology, European Institute of Oncology, Milan, Italy.
Alberto
A
Luini
Division of Senology, European Institute of Oncology, Milan, Italy.
Mattia
M
Intra
Program of Senology (Breast Health), European Institute of Oncology, Milan, Italy.
Aron
A
Goldhirsch
Division of Medical Senology, European Institute of Oncology, Milan, Italy.
Marco
M
Colleoni
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy*
D015251:Epirubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil
Chemotherapy; Ki-67; Metronomic therapy; Neoadjuvant; Pathological complete response