Centre Jean Perrin, Division de Recherche Clinique, Université d'Auvergne, Centre d'Investigation Clinique, Clermont-Ferrand, France.
Cancer Biol Ther. 2010 Jan;9(1):8-14. doi: 10.4161/cbt.9.1.10392. Epub 2010 Jan 21.
Since the improvement of chemotherapy with safe molecules is needed for a better efficacy without supplementary toxicity, we investigated the feasibility and tolerability of the combination of docetaxel and curcumin, a polyphenolic derivative extracted from Curcuma longa root.
Fourteen patients were accrued in this open-label phase I trial. At the last dose level of curcumin, three dose-limiting toxicities were observed and two out of three patients at this dose level refused to continue treatment, leading us to define the maximal tolerated dose of curcumin at 8,000 mg/d. Eight patients out of 14 had measurable lesions according to RECIST criteria, with five PR and three SD. Some improvements as biological and clinical responses were observed in most patients.
Patients with advanced or metastatic breast cancer were eligible. Docetaxel (100 mg/m(2)) was administered as a 1 h i.v. infusion every 3 w on d 1 for six cycles. Curcumin was orally given from 500 mg/d for seven consecutive d by cycle (from d-4 to d+2) and escalated until a dose-limiting toxicity should occur. The primary endpoint of this study was to determine the maximal tolerated dose of the combination of dose-escalating curcumin and standard dose of docetaxel chemotherapy in advanced and metastatic breast cancer patients. Secondary objectives included toxicity, safety, vascular endothelial growth factor and tumor markers measurements and assessment of objective and clinical responses to the combination therapy.
The recommended dose of curcumin is 6,000 mg/d for seven consecutive d every 3 w in combination with a standard dose of docetaxel. From the encouraging efficacy results, a comparative phase II trial of this regimen plus docetaxel versus docetaxel alone is ongoing in advanced and metastatic breast cancer patients.
为了提高化疗的效果，同时又不增加额外的毒性，需要使用安全的分子，因此我们研究了多西紫杉醇与姜黄素联合应用的可行性和耐受性，姜黄素是从姜黄根茎中提取的多酚衍生物。
这项开放性、Ⅰ期临床试验共入组 14 例患者。在姜黄素的最大耐受剂量水平，观察到 3 例剂量限制性毒性，其中 2 例患者拒绝继续治疗，因此我们确定姜黄素的最大耐受剂量为 8000mg/d。14 例患者中 8 例有可测量病灶，根据 RECIST 标准，其中 5 例为部分缓解，3 例为疾病稳定。大多数患者出现了一些生物和临床应答方面的改善。
入组标准为晚期或转移性乳腺癌患者。多西紫杉醇（100mg/m2）静脉滴注 1 小时，每 3 周 1 次，共 6 个周期。姜黄素 500mg/d 口服，连续 7 天给药（从 d-4 到 d+2），剂量逐渐递增，直至出现剂量限制性毒性。该研究的主要终点是确定晚期和转移性乳腺癌患者中多西紫杉醇联合剂量递增姜黄素的最大耐受剂量。次要终点包括毒性、安全性、血管内皮生长因子和肿瘤标志物的测量以及联合治疗的客观和临床应答的评估。
推荐的剂量是姜黄素 6000mg/d，连续 7 天，每 3 周 1 次，与标准剂量的多西紫杉醇联合应用。根据令人鼓舞的疗效结果，一项比较该方案联合多西紫杉醇与多西紫杉醇单药治疗晚期和转移性乳腺癌患者的Ⅱ期临床试验正在进行中。
