Table 4.
Natural products in clinical trials for cancer treatment.
| NPs (Source) | Tumor Type |
Phase | Patient Number | Parameters | Results | References and CT Number |
|---|---|---|---|---|---|---|
| Curcumin (Curcuma longa) |
Myeloma | I | 15 | Patients displaying intolerance to dexamethasone treated with curcumin (3.0–4.0 g/day oral administration) plus immunomodulatory drugs (IMD, lenalidomide) or proteasome inhibitors (PI, bortezomib) for about 6 years. | Curcumin in combination with IMD or PI lessened paraprotein (38%) and plasmacytosis (59%) levels; 12 out of 15 patients were stable. | [189] |
| Myeloma and prostate | II | 40 | Patients were treated with curcumin (4 g) plus piperidine (5 mg) by oral administration for 12 months. | No posted results. First results will be posted after May 2023. | NCT04731844 | |
| Myeloma | IIa | 33 | The treated patient group (17) was treated with curcumin (8 g/day) for 28 days plus melphalan (4 mg/m2) and prednisone (40 mg/m2) for 7 days. Control patient group (16) was treated with melphalan, prednisone, and a placebo. The two groups received 4 cycles of treatment. | The treated group displayed an increased overall remission with a reduction in IL-6, VEGF, and TNF-α levels compared with the control group. | [190] ISRCTN14131419 |
|
| Metastatic breast cancer | II | 150 | Treated patient group was treated with intravenous curcumin (300 mg) and paclitaxel (80 mg/m2) weekly for 12 weeks. Control patient groups were treated with paclitaxel and a placebo. | Tumor reduction by 50.7% in curcumin treatment compared with 33.3% placebo. | [191] NCT03072992 |
|
| Obese women characterized by high risk of developing breast cancer | I | 29 | The participants received curcumin (50 or 100 mg) by oral administration twice daily for 3 months. | No posted results. | NCT01975363 | |
| Breast cancer patients before surgery | Not applicable | 30 | Patients were treated with 8 g per day by oral administration for two to four weeks before surgery. | No posted results. | NCT03847623 | |
| Breast cancer patients treated with radiotherapy | II/III | 686 | Patients were treated with curcumin (6.0 g) by oral administration daily for the entire period of the radiation treatments plus another week. | Breast cancer patients treated with curcumin displayed a reduced dermatitis severity. | NCT01246973 | |
| Metastatic colorectal cancer | IIa | 41 | Treated patient group was treated with curcumin (2 g/day) orally administered plus standard chemotherapy (FOLFOX) every 2 weeks for 12 cycles. | The clinical trial assessed the safety and effect of curcumin in combination with FOLFOX-based chemotherapy in metastatic colorectal cancer patients. | [192] NCT01490996 |
|
| EGCG | Ovarian cancer | II | 300 | Five treatment arms: (i) Combined treatment (TP: paclitaxel 175 mg/m2 plus cisplatin 75–100 mg/m2 by intravenous administration, or TC: paclitaxel 175 mg/m2 plus carboplatin AUC 5 by intravenous administration, plus surgery plus postoperative TP or TC regimen) in combination with I3C (200 mg/day) continuously; (ii) combined treatment plus I3C (200 mg/day) and EGCG (200 mg/day) continuously; (iii) combined treatment plus I3C and EGCG continuously and TP therapy; (iv) combined treatment without TP or TC postoperative regimen; (v) combined treatment. | Patients treated with I3C and EGCG plus chemotherapy showed an increased median overall survival (60 months) and median progression-free survival (48.5 months) compared with single treatment and chemotherapy alone. Moreover, I3C and EGCG treatment reduced cancer recurrence. | [193] ACTRN12616000394448 |
| Lung cancer | II | 83 | Prophylactic EGCG group: EGCG (440 umol/L) 0.9% saline solution 3 times/day at the beginning of radiotherapy treatment; therapeutic EGCG group: EGCG 0.9% saline solution 3 times/day in presence of grade 1 esophagitis radiotherapy side effects; conventional therapy group: mLDG (lidocaine 0.16 mg/mL, dexamethasone 0.02 mg/mL, and gentamycin 0.16 mg/mL) 3 times/day in presence of grade 1 esophagitis radiotherapy side effects. | Compared to standard therapies, EGCG preventive treatment and EGCG administration in radiation-treated patients reduced the severity of esophagitis and the levels of pro-inflammatory factors in the serum. | [194] NCT02577393 |
|
| Esophageal Cancer | I | 15 | Six escalating doses (880 umol/L–4400 umol/L) of EGCG weredissolved in 0.9% saline solution and administered three times a day. EGCG solution was given continuously for 8 days before anti-tumor treatment. | No posted results (ongoing trial). | [195] NCT05039983 |
|
| EGCG (Polyphenon E) | Bladder cancer | II | 31 | An amount of 800–1200 mg/day of orally administered EGCG for 14–28 days prior to surgery. | The dose-dependent downregulation of two tumor biomarkers, clusterin (an apoptosis marker) and PCNA (a proliferation marker), was seen in EGCG-treated patients, supporting the compound’s chemoprotective activity and use as a neoadjuvant therapy before transurethral resection of bladder tumor or cystectomy, despite the fact that there are no differences in EGCG tumor levels between EGCG-treated and placebo patient groups. | [196] |
| Breast cancer | II | 32 | Subjects are asked to take 4 polyphenol E (200 mg) capsules daily with a meal for the duration of the study. Biomarkers are measured at baseline and then again at presurgery, the end-point for the study within a time frame between 4 and 6 weeks. | Polyphenon E neoadjuvant daily administration induced a decreasein serum HGF levels, without altering those of VEGF. |
NCT00676793 |
|
| Breast cancer | Ib | 40 | After completing adjuvant therapy, women with stage I–III breast cancer were randomized to receive Poly E at dosages of 400, 600, or 800 mg twice daily for six months, or a placebo. Samples of blood and urine were collected at the beginning, 2, 4, and 6 months. | After completing adjuvant therapy, women with stage I–III breast cancer were randomized to receive Poly E at dosages of 400, 600, or 800 mg twice daily for six months, or a placebo. Samples of blood and urine were collected at the beginning, 2, 4, and 6 months. | [197] | |
| Resveratrol | Breast cancer | I | 39 | Resveratrol (5–50 mg) was orally administered for 3 months, twice a day. | After resveratrol treatment, no significant changes in p16, CCND2, APC, and RASSF-1α DNA methylation wereobserved, but only a decreased methylation profile of RASSF-1α and an increase inthe APC profile. | [199] |
| Prostate cancer | I | 14 | Patients were treated with 500 to 4000 mg of muscadine grape extract (MPX, containing 1.2 mg of ellagic acid, 9.2 g of quercetin, and 4.4 g of trans-resveratrol) per day, taken orally for 28 days, with a follow-up of >2 years. | No tolerability problems were observed in patients, and the treatment was deemed to be safe. Additionally, it demonstrated a delay in the recurrence process by extending the PSA doubling time (PSADT) by 5.3 months. | [200] | |
| Prostate cancer | I | 112 | Following stratification based on their initial PSADT and Gleason scores, the participants were randomly allocated 1:2:2 to receive a placebo, 500 mg of MPX (low), or 4000 mg of MPX (high), daily. | There was no discernible difference between the control and MPX-treated cohorts in the time it took for PSA to double. | [201] NCT00256334 |
|
| Colorectal cancer | I | 8 | Resveratrol was administered at 20 and 80 mg/day. Resveratrol-containing freeze-dried grape powder (GP) was administered at 0.073 and 0.114 mg/day. Both treatments were taken orally. | Resveratrol/GP treatment significantly inhibited Wnt target gene expression (myc, jun, TCF7, cyclin D1, axin II) in healthy colonic mucosa without effects on tumor mucosa. | [202] | |
| Colorectal cancer | I | 9 | A 5.0 g daily dose for 14 days of SRT501 (micronized form of resveratrol), was administered to patients with colorectal cancer and hepatic metastases who were scheduled to undergo hepatectomy. | This treatment method increased drug availability and absorption. After 1–2 weeks of therapy with resveratrol or SRT501, the observed amounts of parent resveratrol and its primary metabolites in the colon tissue of patients were comparable to the efficacious doses of resveratrol utilized in pre-clinical investigations. In addition, cleaved caspase-3, an indication of death, dramatically increased in malignant hepatic tissue after SRT501 therapy by 39% in comparison to tissue from patients who received a placebo. | [203] | |
| Colorectal cancer | I | 20 | Colorectal cancer patients were treated daily with resveratrol (0.5 or 1.0 g) for 8 days before surgery. | Treatment reduced ki-67 levels. | [204] NCT00433576 |
|
| Vincristine | Low-grade glioma | I | 497 | A total of 497 patients were randomized to receive vincristine carboplatin (VC, vincristine 1.5 mg/m2 × 10 weekly and carboplatin 550 mg/m2 q 3 weekly) (n = 249) or VC plus etoposide (VCE, etoposide 100 mg/m2, days 1, 2,and 3). | The high rates of non-progression after 24 weeks support the use of VC as a first-line treatment. | [210] European Union Clinical Trials Register No. 2005-005377-29 |
| Diffuse large B-cell lymphoma | II | 120 | Patients underwent a pre-treatment phase consisting of oral prednisone (60 mg total dosage commencing 1 week before cycle 1, for 4 days (day7 to day4)) and oral vincristine before the first cycle of the ofatumumab (1000 mg every 3 weeks) + miniCHOP regimen (400 mg/m2 of intravenous cyclophosphamide, 25 mg/m2 of intravenous doxorubicin, 1 mg/m2 of intravenous vincristine on day 1 of each cycle, and 40 mg/m2 of oral prednisone every day from days 1 to 5). | The pretreatment with ofatumumab and miniCHOP in 80-year-old patients improved overall survival in comparison with standard therapy. | [211] NCT001195714 |
|
| Bryostatin-1 | Renal cell carcinoma | II | 30 | Patients were treated for 30 min with an intravenous infusion of bryostatin-1 (25 microg/m2) with formulation PET (polyethyleneglycol, ethanol, and Tween 80) on days 1, 8, and 15 of each 28-day cycle. | Patients responded to the treatment without severe adverse effects. | [213] |
| Low-grade non-Hodgkin lymphoma and chronic lymphocytic leukemia | II | 25 | Patients were treated for 72 h with a continuous infusion of bryostatin-1 (120 microg/m2) per course every 2 weeks immediately followed by vincristine (from 0.5 mg/m2 to 2 mg/m2) administration by bolus i.v. injection. | Treatment with bryostatin-1 resulted in one patient in complete remission and two in partial remission. Moreover, this treatment promoted a differentiative state of CLL cells, demonstrated bythe presence of CD11c/CD22/CD20 B-cell subpopulations. | [214] | |
| Sulforaphane | Prostate cancer | nd | 98 | Patients were treated with BSE (200 µmol daily) or a placebo for 4–8 weeks. | Forty differently expressed genes linked to BSE treatment, including the downregulation of two prostate cancer-related genes. Supplementing with BSE is associated with alterations in gene expression but not with changes in prostate tissue biomarkers. | [215] (NCT01265953) |
| Prostate cancer | II | 61 | Patients were given a weekly 300 mL serving of soup produced from either regular broccoli (the control) or one of two experimental broccoli genotypes with increased glucoraphanin concentrations that delivered 3 or 7 times the amount of the control, respectively. | Downregulation of genes linked to inflammation processes and epithelial–mesenchymal transition in a dose-dependent manner in glucoraphanin-rich broccoli-soup-consuming men. An inverse relationship was found between the consumption of cruciferous vegetables and a decreased risk of prostate cancer advancement in males under active monitoring. | [216] (NCT01950143) | |
| Fisetin | Colorectal cancer | I | 38 | CRC patients treated with chemotherapy were randomized to receive either 100 mg fisetin (n = 18) or placebo (n = 19) for 7 weeks. | After fisetin administration to CRC patients, plasma levels of IL-8 and hs-CRP dropped dramatically as a lower expression of MMP-7. | [217] (code: IRCT2015110511288N9) |
Abbreviations: IMD, immunomodulatory drugs, PI, proteasome inhibitor, VEGF, vascular endothelial growth factor, IL-6, interleukine-6, TNF-α, tumor necrosis factor-α, FOLFOX, leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin., EGCG, epigallocatechin-3-gallate, TC, taxotere and cyclophosphamide, TP, docetaxel plus cisplatin, PCNA, proliferating cell nuclear antigen, HGF, hepatocyte growth factor, CCND2, Cyclin D2, APC, WNT signaling pathway regulator, RASSF-1α, Ras association domain-containing protein 1 I, TCF7, Transcription Factor 7, SRT501, micronized form of resveratrol, miniCHOP, mini-cyclophosphamide, doxorubicin, vincristine, and prednisone, CLL, chronic lymphocytic leukemia BSE, broccoli sprout extract, CRC, colorectal cancer.