Table 2.
Clinical trials studied in natural compound for chemoprevention and treatment of colorectal cancer.
| Agent | Combination strategy | Volunteer(n) | Phage | Trial No. | Status | Administration | Doses | Main outcomes | REF |
|---|---|---|---|---|---|---|---|---|---|
| Curcumin | FOLFOX | Metastatic colorectal cancer, 12 | I | NCT01490996 | Completed | Orally | 0.5, 1, 2g/day | Safety and tolerability for curcumin in combination with FOLFOX chemotherapy | (208) |
| Curcumin | Healthy volunteer, 24 (34) |
I | FWA 00004969 | Completed | Orally | 500,1000,2000,4000,6000,8000,10000,12000mg(in single oral dose) | The tolerance in single oral doses up to 12,000 mg appears to be excellent | (209) | |
| Curcumin | FOLFOX | Metastatic colorectal cancer, 27 (28) | II | NCT01490996 | Completed | Orally | 2g | Safe and tolerable adjunct to FOLFOX chemotherapy | (203) |
| Curcumin | Familial adenomatous polyposis, 44 | II | NCT00641147 | Completed | Orally | 3000 mg/d (twice per day for 12 months.) | No difference in the mean number or size of lower intestinal tract adenomas between patients given curcumin 3,000 mg/day and those given placebo for 12 weeks. | (210) | |
| Curcuminoid | Anthocyanin | patients with adenomatous polyps of the colon, 29 (35) | II | NCT01948661 | Completed | Orally | 200mg/d (twice per day for 4–6 weeks) | Combining anthocyanins and curcumin lead to a potentially favorable modulation of tissue biomarkers of inflammation and proliferation in colon adenomas. | (32) |
| Curcuminoid | CRC stage 3, 67 (72) |
II | ? | Completed | Orally | 500mg/d (twice per day for 8 weeks) | Improve ESR and serum levels of CRP in stage-3 CRC subjects and improve the global quality of life and functional scales compared to placebo. | (211) | |
| Liposomal curcumin | Healthy volunteer,50 | I | NCT01403545 | Completed | Vessel injection | 120 mg/m2 (10 - 400 mg/m2; n = 2 - 6 per group) | Safe up to a dose of 120 mg/m2. | (212) | |
| Liposomal curcumin | Locally advanced or metastatic cancer,32 | I | NCT02138955 | Completed | Vessel injection | 300 mg/m2 over 6 h was the maximum tolerated dose | 300 mg/m2 liposomal curcumin over 6 h was the maximum tolerated dose in heavily pretreated patients, with significant tumor marker responses and transient clinical benefit | (204) | |
| GTE (green tea extract) | Risk for CRC, 30 (61) | II | ACTRN12613000097741 | Completed | Orally | GTE capsules (800 mg EGCG/d) for 6 weeks | GTE regulates targeted biomarkers related to CRC oncogenesis, specifically genes associated inflammation (NF-κB) and methylation (DNMT1). | (16) | |
| Poly E | Colorectal adenomas or cancer, 32 (39) | II | -- | Completed | Orally | 1200mg Poly E/d for 6 months(containing 65% EGCG) | Well tolerated, but did not significantly reduce the number of rectal aberrant | (207) | |
| Resveratrol | Resectable colorectal cancer, 20 | II | -- | Completed | Orally | 0.5g RES/d or 1.0g RES/d for 8 days | Resveratrol exerted a small reduction in cell proliferation in colorectal tissue after | (213) | |
| ingestion,but the biological importance of such a slight decrease is debatable. | |||||||||
| SRT501 | Stage IV colorectal cancer, 9 | -- | NCT00920803 | Completed | Orally | 5.0 g/d for 10-21 day | i. its daily consumption for 14 days seems to be well tolerated in colorectal cancer patients, ii. Cmax for SRT501 was higher than reported for equivalent dose of non-micronised resveratrol, iii. its ingestion furnished measurable resveratrol levels in a tissue distant to the GI tract (in particular the liver), and these concentrations were accompanied by a significant pharmacological effect. | (205) | |
| EGCG+ apigenin |
Patients with resected colon cancer, 87 (160) | -- | -- | Completed | Orally | 20 mg apigenin and 20 mg EGCG for 3-4 years | Reduce the recurrence rate of colon neoplasia in patients with resected colon cancer. | (206) | |
| Curcumin+ quercetin |
Familia ladenomatous polyposis, 5 | -- | -- | Completed | Orally | curcumin 1440mg/d+ quercetin 60mg/d for 6 months |
Reduce the number and size of ileal and rectal adenomas in patients with FAP without appreciable toxicity. | (214) | |
| Genistein | FOLFOX or FOLFOX-Bevacizumab | Metastatic colorectal cancer, 13 (14) | I/II | NCT01985763 | Completed | Orally | 60mg/d | Safe and tolerable. | (215) |
| Isoflavones | Adenomatous polyps, 125(150) | -- | -- | Completed | Orally | 58 g protein powder/d containing 83 mg isoflavones or ethanol-extracted soy-protein powder containing 3 mg isoflavones for 12 months | Supplementation with soy protein containing isoflavones does not reduce colorectal epithelial cell proliferation in the cecum, sigmoid colon, and rectum and increases cell proliferation measures in the sigmoid colon. | (216) | |
| GCP (genistein combined polysaccharide) | Healthy volunteer,8 | -- | -- | Completed | Orally | -- | serum concentrations of genistein in the subjects treated with GCP (n = 4) at 3 h after administration were significantly higher than those in the subjects treated with SBE (n = 4). | (217) |