Dellapasqua Silvia, Bertolini Francesco, Bagnardi Vincenzo, Campagnoli Elisabetta, Scarano Eloise, Torrisi Rosalba, Shaked Yuval, Mancuso Patrizia, Goldhirsch Aron, Rocca Andrea, Pietri Elisabetta, Colleoni Marco
Medical Senology Research Unit and Division of Medical Oncology, Department of Medicine, European Institute of Oncology, Milan, Italy.
J Clin Oncol. 2008 Oct 20;26(30):4899-905. doi: 10.1200/JCO.2008.17.4789. Epub 2008 Sep 15.
Metronomic chemotherapy has shown efficacy in patients with metastatic breast cancer. When used in association with targeted antiangiogenic drugs, it was more active than metronomic therapy alone in preclinical and clinical studies.
Patients with advanced breast cancer were candidates to receive metronomic oral capecitabine (500 mg thrice daily) and cyclophosphamide (50 mg daily) plus bevacizumab (10 mg/kg every 2 weeks).
In 46 assessable patients, we observed one complete response (CR; 2%), 21 partial responses (PR; 46%), 19 patients (41%) with stable disease (SD), and five patients (11%) with progressive disease, for an overall response rate of 48% (95% CI, 33% to 63%). Additional long-term disease stabilization (SD > or = 24 weeks) occurred in eight patients, for an overall clinical benefit (CR + PR + SD > or = 24 weeks) of 68% (95% CI, 51% to 81%). Median time to progression was 42 weeks (95% CI, 26 to 72 weeks). Toxicity was generally mild. Grade 3 or 4 nonhematologic adverse effects included hypertension (n = 8), transaminitis (n = 2), and nausea/vomiting (n = 2). Higher baseline circulating endothelial cells (CECs) were correlated with overall response (P = .02), clinical benefit (P = .01), and improved progression-free survival (P = .04).
Treatment with metronomic capecitabine and cyclophosphamide in combination with bevacizumab was effective in advanced breast cancer and was minimally toxic. The number of baseline CECs significantly correlated with response and outcome, therefore supporting further studies on this surrogate marker for the selection of patients to be candidates for antiangiogenic treatments.
节拍化疗已在转移性乳腺癌患者中显示出疗效。在临床前和临床研究中，当与靶向抗血管生成药物联合使用时，其比单纯节拍化疗更具活性。
晚期乳腺癌患者接受口服节拍卡培他滨（每日3次，每次500 mg）和环磷酰胺（每日50 mg）加贝伐单抗（每2周10 mg/kg）治疗。
在46例可评估患者中，我们观察到1例完全缓解（CR；2%），21例部分缓解（PR；46%），19例疾病稳定（SD；41%），5例疾病进展（11%），总缓解率为48%（95%CI，33%至63%）。另外8例患者出现了长期疾病稳定（SD≥24周），总临床获益率（CR+PR+SD≥24周）为68%（95%CI，51%至81%）。中位疾病进展时间为42周（95%CI，26至72周）。毒性一般较轻。3级或4级非血液学不良反应包括高血压（n = 8）、转氨酶升高（n = 2）和恶心/呕吐（n = 2）。较高的基线循环内皮细胞（CEC）与总缓解（P = 0.02）、临床获益（P = 0.01）及无进展生存期改善（P = 0.04）相关。
节拍卡培他滨和环磷酰胺联合贝伐单抗治疗晚期乳腺癌有效且毒性极小。基线CEC数量与缓解和预后显著相关，因此支持进一步研究将此替代标志物用于选择抗血管生成治疗的候选患者。
