Institute of Experimental Genetics, School of Medical Sciences, National University of Rosario, Argentina.
Future Oncol. 2013 Mar;9(3):451-62. doi: 10.2217/fon.12.196.
Metronomic chemotherapy (MCT), the chronic administration, at regular intervals, of low doses of chemotherapeutic drugs without extended rest periods, allows chronic treatment with therapeutic efficacy and low toxicity. Our preclinical results suggested that combined MCT with cyclophosphamide and celecoxib could inhibit breast cancer growth. The aim of this study was to determine the toxicity, safety and efficacy of oral MCT with cyclophosphamide 50 mg per orem daily and celecoxib 400 mg (200 mg per orem two-times a day) in advanced breast cancer patients. During the first stage of the study, the therapeutic response consisted of prolonged stable disease for ≥24 weeks in six out of 15 (40%) patients with a median duration of 37.5 weeks and a partial response in one out of 15 (response rate: 6.7%) patients lasting 6 weeks. The overall clinical benefit rate was 46.7%. The median time to progression was 14 weeks. Progression-free survival at 24 weeks was 40% and the 1-year overall survival rate was 46.7%. The adverse events were mild (gastric, grade 1; and hematologic, grade 1 or 2). No grade 3 or 4 toxicities were associated with the treatment. Evaluation of patients' quality of life showed no changes during the response period. MCT with cyclophosphamide plus celecoxib is safe and shows a therapeutic effect in advanced breast cancer patients.
节拍化疗（MCT），即定期、小剂量、无延长间歇期地给予化疗药物，可以实现慢性治疗并具有疗效且毒性低。我们的临床前研究结果表明，MCT 联合环磷酰胺和塞来昔布可以抑制乳腺癌生长。本研究旨在确定口服环磷酰胺 50mg/次和塞来昔布 400mg（200mg/次，每日 2 次）的 MCT 在晚期乳腺癌患者中的毒性、安全性和疗效。在研究的第一阶段，15 例患者中有 6 例（40%）的治疗反应为≥24 周的持续稳定疾病，中位持续时间为 37.5 周，1 例（反应率：6.7%）患者出现持续 6 周的部分缓解。总体临床获益率为 46.7%。中位无进展生存期为 14 周。24 周无进展生存率为 40%，1 年总生存率为 46.7%。不良反应轻微（胃部，1 级；血液学，1 级或 2 级）。无 3 级或 4 级毒性与治疗相关。对患者生活质量的评估显示，在缓解期间没有变化。环磷酰胺联合塞来昔布的 MCT 安全有效，可用于晚期乳腺癌患者。
