表柔比星、顺铂和持续输注氟尿嘧啶序贯每周紫杉醇联合节拍性环磷酰胺作为三阴性乳腺癌术前治疗的II期研究

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.

作者信息

Cancello Giuseppe, Bagnardi Vincenzo, Sangalli Claudia, Montagna Emilia, Dellapasqua Silvia, Sporchia Andrea, Iorfida Monica, Viale Giuseppe, Barberis Massimo, Veronesi Paolo, Luini Alberto, Intra Mattia, Goldhirsch Aron, Colleoni Marco

机构信息

Division of Medical Senology, European Institute of Oncology, Milan, Italy.

Division of Epidemiology and Biostatistics, European Institute of Oncology, and Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy.

出版信息

Clin Breast Cancer. 2015 Aug;15(4):259-65. doi: 10.1016/j.clbc.2015.03.002. Epub 2015 Mar 18.

DOI:10.1016/j.clbc.2015.03.002

PMID:25933934

Abstract

BACKGROUND

The aggressive biological behavior and the lack of target therapy prompts the search for new therapeutic approaches for triple-negative breast cancers.

PATIENTS AND 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.

CONCLUSION

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.

摘要

背景

三阴性乳腺癌侵袭性的生物学行为以及缺乏靶向治疗促使人们寻找新的治疗方法。

患者与方法

我们评估了基于节拍原则的新辅助治疗方案的疗效，包括Ki-67变化和临床反应，以及毒性。该方案为ECF（表柔比星与顺铂在第1天使用，低剂量氟尿嘧啶持续输注，每21天1个疗程，共4个疗程），随后每28天在第1、8和15天给予紫杉醇（90mg/m²），共3个疗程，并联合口服节拍环磷酰胺50mg/d，持续12周，用于雌激素受体和孕激素受体<10%的HER2阴性乳腺癌（T2-T4a-d，N0-3，M0）患者。

结果

2009年6月至2013年5月，我们招募了34例患者。所有患者均按意向性分析原则进行评估。手术切除标本与治疗前肿瘤核心活检中评估的Ki-67阳性细胞百分比的平均差异在总体人群中为41%（95%置信区间[CI]，30-51；P<.0001），在未达到病理完全缓解（pCR）的患者中为22%（95%CI，7-38；P=.0097）。31例患者（91%）获得了治疗反应，19例患者（56%；95%CI，35-70）达到了pCR。3例患者病情稳定，无患者疾病进展。≥3级血液学不良事件包括9%（34例中的3例）的患者出现白细胞减少、38%（34例中的'13例）的患者出现中性粒细胞减少以及3%（34例中的1例）的患者出现贫血。非血液学≥3级毒性仅1例患者出现口腔炎。