A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer
A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer
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DOI：
10.1007/s00280-010-1470-2
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发表时间：
2011-07-01
影响因子：
3
通讯作者：
Aggarwal, Bharat B.
中科院分区：
文献类型：
--
作者：
Kanai, Masashi;Yoshimura, Kenichi;Aggarwal, Bharat B.
姜黄素是一种从植物中提取的天然多酚，具有与细胞毒性药物协同作用，是一种很有前景的抗癌药物。我们评估了姜黄素与吉西他滨为基础的化疗联合治疗的安全性和可行性。耐吉西他滨胰腺癌患者每日口服8克姜黄素并联合以吉西他滨为基础的化疗。主要终点是I期的安全性和II期口服姜黄素的可行性。21名患者入组。在I期研究中未观察到剂量限制性毒性，口服姜黄素8g /天被选为II期研究的推荐剂量。没有患者因为姜黄素的不耐受而退出本研究，达到了II期研究的主要终点，口服姜黄素的中位依从率为100%（范围79-100%）。姜黄素起始治疗后的中位生存时间为161天（95%置信区间为109-223天），1年生存率为19%（4.4-41.4%）。5例患者的血浆姜黄素水平在29 - 412 ng/ml之间。每日口服8g姜黄素与吉西他滨为基础的化疗联合治疗对胰腺癌患者是安全可行的，其疗效有待进一步研究。
Curcumin, a plant-derived natural polyphenol, could be a promising anti-cancer drug and shows synergic effects with cytotoxic agents. We evaluated the safety and feasibility of combination therapy using curcumin with gemcitabine-based chemotherapy.Gemcitabine-resistant patients with pancreatic cancer received 8 g oral curcumin daily in combination with gemcitabine-based chemotherapy. The primary endpoint was safety for phase I and feasibility of oral curcumin for phase II study.Twenty-one patients were enrolled. No dose-limiting toxicities were observed in the phase I study and oral curcumin 8 g/day was selected as the recommended dose for the phase II study. No patients were withdrawn from this study because of the intolerability of curcumin, which met the primary endpoint of the phase II study, and the median compliance rate of oral curcumin was 100% (Range 79-100%). Median survival time after initiation of curcumin was 161 days (95% confidence interval 109-223 days) and 1-year survival rate was 19% (4.4-41.4%). Plasma curcumin levels ranged from 29 to 412 ng/ml in five patients tested.Combination therapy using 8 g oral curcumin daily with gemcitabine-based chemotherapy was safe and feasible in patients with pancreatic cancer and warrants further investigation into its efficacy.