Table 1.

Completed clinical trials using curcumin

Type	Method and material	Results and Conclusion	Reference
Phase I Safety trial	Patients: 10, 2000 mg/day + piperine 20 mg/kg;	Piperine, a known inhibitor of hepatic and intestinal glucuronidation enhanced serum concentration, extent of absorption, and bioavailability. Much higher concentration with piperine at 1/4 to 1 h post drug (P < 0.01 at 0.25 h and 0.5 h; P < 0.001 at 1 h)	Shoba et al. 1998 (58)
Phase I Safety trial	Patients: 25, Oral 500–12,000 mg/d for 90 days Bx done after treatment	Oral curcumin is not toxic to humans up to 8,000 mg/d for 3 months. Histologic improvement of precancerous lesions were observed in bladder cancer, oral leukoplakia, intestinal metaplasia of the stomach, CIN, and Bowen’s disease	Cheng et al. 2001 (59)
Phase I Colon cancer	Patients: 15, Oral curcumin extract of 440–2200 mg/d for 120 days. Activity of GST and levels of M1G were measured.	Safe administration of curcumin extract at doses up to 2.2 g daily, equivalent to 180 mg of curcumin. Curcumin has low oral bioavailability in humans and may undergo intestinal metabolism. Lowered GST (Glutathione-S-transferase) with constant M1G.	Sharma et al. 2001 (60)
Phase I Colorectal cancer	Patients: 15, Oral 450–3600 mg/d for 120 days. Dose-escalation study. Levels of curcumin and its metabolites in plasma, urine, and feces were measured.	Lowered inducible serum PGE2 levels (P < 0.05). No dose-limiting toxicity. A daily oral dose of 3.6 g of curcumin is advocated for Phase II evaluation in the cancer prevention outside the gastrointestinal tract. Levels of curcumin and its metabolites in the urine can be used to assess general compliance.	Sharma et al. 2004 (61)
Phase I Colorectal cancer	Patients: 12, Oral 450–3600 mg/d for 7 days. Bx samples of normal and malignant colorectal tissue, at diagnosis and at 6 to 7 hours after last dose of curcumin.	M1G levels were 2.5-fold higher in malignant tissue as compared with normal tissue (P < 0.05 by ANOVA). The concentrations in normal and malignant colorectal tissue of patients receiving 3,600 mg of curcumin were 12.7±5.7 and 7.7±1.8 nmol/g, respectively. The daily dose of 3.6 g curcumin achieves pharmacological efficacy in the colorectum with negligible distribution of curcumin outside the gut.	Garcea et al. 2005 (62)
Phase I Safety trial	Patients: 24, Oral 500–12,000 mg/day. Dose-escalation study for MTD and safety	Seven of 24 subjects (30%) experienced only minimal toxicity. Systemic bioavailability of curcumin or its metabolites may not be essential for CRC chemoprevention because CRC can still benefit from curcumin.	Lao et al. 2006 (63)
Phase I Open-label Advanced metastatic breast cancer	Patients: 14, Docetaxel (100 mg/m2) 1 h i.v. every 3 wk on d 1 x six cycles + Oral 500 mg/d for 7 consecutive days and escalated the dose until toxicity. VEGF, and tumor markers measured	MTD at 8,000 mg/d 8/14 patients had measurable lesions, with 5 PR and 3 SD. Some biological and clinical responses were observed in most patients. The recommended dose of curcumin is 6,000 mg/d for seven consecutive d every 3 wk in combination with a standard dose of docetaxel.	Bayet-Robert et al. 2010 (64)
Phase II Efficacy trial Skin lesion	Patients: 62, 1% ointment, several months for “External cancerous lesion”	The first clinical study. Reduction in smell in 90% patients, reduction of itching in all cases, dry lesions in 70% patients, reduction in lesion size and pain in 10% patients.	Kuttan et al. 1987 (17)
Phase II FAP	Patients: 5, Oral curcumin 480g + quercetin 20 mg tid for 180 days. Polyps size and # assessed	Decrease in the number of polyps was seen in 60.4% Decrease in the size of polyps was 50.9% in FAP patients. RCT in the future are necessary	Cruz-Correa et al. 2006 (65)
Cohort study PIN	Patients: 24	Zyflamend, a novel herbal anti-inflammatory mixture, as a potential chemoprevention agent in a phase I trial for patients diagnosed with PIN.	Rafailov et al. 2007 (66)
Phase IIa	Patients: 44	40% reduction in ACF numbers with 4g dose	Carroll et al. (67)