节拍性环磷酰胺和多西他赛方案在去势抵抗性前列腺癌中的功能和药效学评估。
Functional and pharmacodynamic evaluation of metronomic cyclophosphamide and docetaxel regimen in castration-resistant prostate cancer.
机构信息
SAFU Department, Regina Elena National Cancer Institute, Via E. Chianesi 53, Rome, Italy.
出版信息
Future Oncol. 2013 Sep;9(9):1375-88. doi: 10.2217/fon.13.99.
AIM
The aim of our study was to investigate the association of docetaxel and metronomic cyclophosphamide (CYC) in castration-resistant prostate cancer (CRPC).
MATERIALS & METHODS: CRPC xenografts were established with PC3 cells. Mice were treated with a combination of CYC (50 mg/kg/day) and docetaxel (10-30 mg/kg/week) or with docetaxel alone. Docetaxel plasma levels were analyzed in patients receiving the drug alone or combined with CYC.
RESULTS
Metronomic CYC is an effective adjuvant in blocking tumor growth in vivo, with comparable efficacy and less toxic effects compared with docetaxel treatment. CYC acts by downregulating cell proliferation and inducing apoptosis thorough upregulation of p21 and inhibition of angiogenesis. Finally, CYC increases docetaxel plasma levels in patients.
CONCLUSION
Metronomic CYC exerts anti-tumoral effects in an in vivo model of prostate cancer and in patients with CRPC, and also increases the bioavailability of docetaxel. These results explain the favorable toxicity and activity profiles observed in patients treated with this regimen.
目的
我们的研究旨在探讨多西紫杉醇和节拍式环磷酰胺（CYC）联合用于去势抵抗性前列腺癌（CRPC）的相关性。
材料与方法
用 PC3 细胞建立 CRPC 异种移植模型。用 CYC（50mg/kg/天）和多西紫杉醇（10-30mg/kg/周）联合或单用多西紫杉醇治疗小鼠。分析单独使用或联合使用 CYC 的患者的多西紫杉醇血浆水平。
结果
节拍式 CYC 是一种有效的辅助药物，可有效阻止体内肿瘤生长，与多西紫杉醇治疗相比，其疗效相当，但毒性作用较小。CYC 通过下调细胞增殖并通过上调 p21 和抑制血管生成诱导细胞凋亡而起作用。最后，CYC 增加了患者体内的多西紫杉醇血浆水平。
结论
节拍式 CYC 在前列腺癌的体内模型和 CRPC 患者中发挥抗肿瘤作用，并增加了多西紫杉醇的生物利用度。这些结果解释了接受该方案治疗的患者观察到的良好毒性和活性特征。
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