ErbB Proteins as Molecular Target of Dietary Phytochemicals in Malignant Diseases

Table 4

EGCG and curcumin in clinical trials.

Phase	Treatment	Subjects	Main findings	Adverse effects	Ref
EGCG
II	319.8 ± 47.9 mg EGCG oral daily from double brewed green tea	16 women in complete remission after ovarian cancer	5 women free of recurrence at 18 months; Not enough evidence to continue the study	Nausea, abdominal pain, vomiting; all adverse effects were of grade 1	[104]
II	1.3 g green tea polyphenols orally, daily, of which 800 mg EGCG was used until prostatectomy	26 men with prostate cancer	EGCG treatment reduced serum levels of HGF, VEGF, IGF-BP3, IGF-I, and PSA	No adverse effects on liver function were observed	[105]
II	500, 750, and 1000 mg/m^2 green tea extracts orally three times a day or placebo	41 patients with oral premalignant lesions	Higher clinical response rate and histologic response rate in treatment group than in placebo; No statistical difference in oral cancer-free survival between the groups	Insomnia (due to caffeine contained in the formulation); Headache; Nausea; Diarrhea	[106]
Ib	200, 400, and 600 mg poly E extract (50–75% EGCG) or placebo	44 patients with Barrett esophagus	400 mg and 600 mg treatment resulted in organ accumulation of EGCG in esophageal mucosa; No significant changes in histological characteristics between cohorts; One placebo subject developed high-grade dysplasia	Abdominal pain/discomfort, diarrhea, loss of energy, nausea, upper respiratory infection, and ALT elevation	[107]
Curcumin
I	0.45 to 3.6 g oral curcumin daily, for 4 months	15 patients with advanced colorectal cancer refractory to treatment	Dose-limiting toxicity was not observed; stable disease after 2 months of treatment (2 patients); significant improvement in quality of life after 1 month of treatment (1 patient)	Serum alkaline phosphatase rise, lactate dehydrogenase rise, mild to acute diarrhea associated with longer administration	[109]
II	8 g oral curcumin daily until disease progression	25 patients with advanced pancreatic adenocarcinoma	One patient stable for > 18 months, another for 8 months, and one patient with a brief, 73% reduction in tumor size	No treatment related toxic effects observed	[173]
II	8 g oral curcumin daily + gemcitabine; 1 g/m^2 i.v. weekly × 3 of 4 wk	17 patients with advanced pancreatic cancer	Out of the 11 evaluable patients, 9% had partial response, 36% had stable disease, and 55% had tumor progression	Abdominal fullness or pain; Mild hematological; toxicity	[112]
I/II	8 g oral curcumin daily,; gemcitabine; 1 g/m^2 i.v. days 1 and 8, S-1 orally for 14 consecutive days every 3 weeks	21 patients with gemcitabine resistant pancreatic cancer	Out of the 18 evaluable patients 28% showed stable disease	Hematological toxicity, fatigue (both probably associated with gemcitabine and not curcumin)	[111]
I	0.5 to 8 g oral curcumin daily + 75 to 100 mg/m^2 docetaxel i.v. every 3 weeks	14 patients with advanced and metastatic breast cancer	5 patients with partial response to the treatment; 3 patients with stable disease	Diarrhea; Hematological toxicity (neutropenia and leucopenia)	[113]
IIa	2 g or 4 g oral curcumin, daily for 30 days	41 patients with >8 aberrant crypt foci, smokers	4 g curcumin dose significantly reduced the number of premalignant lesions by 40%	Toxicity (grade 1 to 3) or diarrhea	[110]