Phase I dose escalation trial of docetaxel plus curcumin in patients with advanced and metastatic breast cancer

 Abstract

Background. Since the improvement of chemotherapy with safe molecules is needed for 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 Patients and methods. Patients with advanced or metastatic breast cancer were eligible. Docetaxel (100 mg/m2) was administered as a 1-hour i.v. infusion every 3 weeks on d1 for 6 cycles. Curcumin was orally given from 500 mg/d for 7 consecutive days 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. Results. Fourteen patients were accrued in this open-label phase I trial. At the last dose level of curcumin, 3 dose-limiting toxicities were observed and 2 out of 3 patients at this dose level refused to continue treatment, leading us to define the maximal tolerated dose of curcumin at 8000 mg/d. Eight patients out of 14 had measurable lesions according to RECIST criteria, with 5 PR and 3 SD. Some improvements as biological and clinical responses were observed in most patients. Conclusion. The recommended dose of curcumin is 6000 mg/d for 7 consecutive days every 3 weeks 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.

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Pages
8 - 14
doi
10.4161/cbt.9.1.10392
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Research Paper
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Phase I dose escalation trial of docetaxel plus curcumin in patients with advanced and metastatic breast cancer