Sharma R A, McLelland H R, Hill K A, Ireson C R, Euden S A, Manson M M, Pirmohamed M, Marnett L J, Gescher A J, Steward W P
Oncology Department, University of Leicester, Leicester LE1 9HN, United Kingdom.
Clin Cancer Res. 2001 Jul;7(7):1894-900.
Curcuma spp. extracts, particularly the dietary polyphenol curcumin, prevent colon cancer in rodents. In view of the sparse information on the pharmacodynamics and pharmacokinetics of curcumin in humans, a dose-escalation pilot study of a novel standardized Curcuma extract in proprietary capsule form was performed at doses between 440 and 2200 mg/day, containing 36-180 mg of curcumin. Fifteen patients with advanced colorectal cancer refractory to standard chemotherapies received Curcuma extract daily for up to 4 months. Activity of glutathione S-transferase and levels of a DNA adduct (M(1)G) formed by malondialdehyde, a product of lipid peroxidation and prostaglandin biosynthesis, were measured in patients' blood cells. Oral Curcuma extract was well tolerated, and dose-limiting toxicity was not observed. Neither curcumin nor its metabolites were detected in blood or urine, but curcumin was recovered from feces. Curcumin sulfate was identified in the feces of one patient. Ingestion of 440 mg of Curcuma extract for 29 days was accompanied by a 59% decrease in lymphocytic glutathione S-transferase activity. At higher dose levels, this effect was not observed. Leukocytic M(1)G levels were constant within each patient and unaffected by treatment. Radiologically stable disease was demonstrated in five patients for 2-4 months of treatment. The results suggest that (a) Curcuma extract can be administered safely to patients at doses of up to 2.2 g daily, equivalent to 180 mg of curcumin; (b) curcumin has low oral bioavailability in humans and may undergo intestinal metabolism; and (c) larger clinical trials of Curcuma extract are merited.
姜黄属植物提取物，尤其是膳食多酚姜黄素，可预防啮齿动物患结肠癌。鉴于关于姜黄素在人体中的药效学和药代动力学的信息稀少，开展了一项新型标准化姜黄提取物的剂量递增试点研究，该提取物为专利胶囊形式，剂量为每天440至2200毫克，含36至180毫克姜黄素。15名对标准化疗难治的晚期结直肠癌患者每天服用姜黄提取物，最长达4个月。在患者血细胞中测量了谷胱甘肽S -转移酶的活性以及由脂质过氧化和前列腺素生物合成的产物丙二醛形成的一种DNA加合物（M(1)G）的水平。口服姜黄提取物耐受性良好，未观察到剂量限制性毒性。在血液或尿液中未检测到姜黄素及其代谢产物，但在粪便中回收了姜黄素。在一名患者的粪便中鉴定出了硫酸姜黄素。摄入440毫克姜黄提取物29天，淋巴细胞谷胱甘肽S -转移酶活性下降了59%。在更高剂量水平时，未观察到这种效应。每位患者的白细胞M(1)G水平保持恒定，且不受治疗影响。5名患者在治疗2至4个月时显示疾病放射学稳定。结果表明：（a）姜黄提取物以每天高达2.2克（相当于180毫克姜黄素）的剂量给予患者时可安全给药；（b）姜黄素在人体中的口服生物利用度较低，可能会经历肠道代谢；（c）值得对姜黄提取物进行更大规模的临床试验。
