Table 4.

Recent clinical use of pharmacological Vitamin C on cancer treatments.

Study	Regimen	Sample (n)	Vc dosage duration (months)	Plasma Vc conc. (mmol/L)	Clinical trial	Diseases	Effect
Drisko et al., 2018	Vc	1	75–125 g 2–3 times per wk, ~ 48	Data not shown	Case report	PAD, stage IV	Body weight↑ tumor size↓liver lesions↓ survived ~ 4 yrs
Schoenfeld et al., 2017	Radiation therapy+ Temozolomide+Vc	11	15–87.5 g 3 times per wk, 9–11	≥20	phase I	GBM	safe and well tolerated PFS and OS↑
	CALGB + Vc	14	75 g twice per wk, ~ 3	16.4 ± 0.5	phase II	NSCLC, stage IIIB and IV	disease control rate, confirmed objective response rate ↑
Hoffer et al., 2015	Surgery Chemotherapy before, Vc	12	1.5 g/kg 2 or 3 times per wk, 1/3–19	10.8 ~ 19.6	phase I-II	#Advanced cancer	Nontoxic minor symptoms, 6 no objective anticancer response, 6 transient stable or longer-lastingstable diseases
Nielsen et al., 2015	Vc	10	5, 30, 60 g once a week, 1	1.8 ~ 19.3	phase II	Metastatic prostate cancer	Safe
Ma et al., 2014	Cp +Pax + Vc	10	15 g 1st shot, 75 or 100 g twice per wk, 12	20 ~ 23	pilot phase 1/2a	Ovarian cancer, stage III, IV	Disease progression/ relapse 8.75 months ↑ toxicities↓
Aldoss et al., 2014	ATO + Vc	11	1 g/day 5 days a wk, 1	Data not shown	Pilot study	non-APL AML	Limited antileukemia activity
Kawada et al., 2014	Vc after CHASER	3	15g 1st shot, 75 or 100 g every other day	>15	Phase I	NHL, stage IIIB, IVA	Safe, no obvious adverse effects
Stephenson et al., 2013	Vc	17	1 g/min 4 days/wk, 1	~ 49	Phase I	advanced cancer, stage I, III, IV	Minimal Adverse effects, no objective anticancer response
Welsh et al., 2013	Gemcitabine + Vc	9	15–125 g twice per wk, 2	≥20	Phase I	metastatic pancreatic cancer, stage IV	PFS and OS↑ Minimal Adverse effects
Monti et al., 2012	Gemcitabine + erlotinib + Vc	14	50–100 g 3 times per wk, 2	16.4, 27.8	Phase I	metastatic pancreatic cancer stage IV	tumor size ↓ Safe with adverse effects
Vollbracht et al., 2011	standard therapy+ Vc	53	7.5 g once a week, 4	Data not shown	Retrospective Cohort Study	BreastcancerUICC stages IIa to IIIb	side effects of disease and therapy↓ Safe
Hoffer et al., 2008	Chemotherapy before, Vc	24	0.4, 0.6, 0.9 1.5 g/kg 3 times per wk, 1	2.4, 4.7, 8.5, 11.3, 17, 26.2	Phase I	%advanced malignancy	Minimal Adverse effects and toxicity, no objective anticancer response
Padayatty et al., 2006	Nephrectomy before, Vc	1	65 g twice per wk, 10	Data not shown	Case report	RCC, nuclear grade III/IV	Complete remission
	Transurethral resection before, Vc	1	30 g twice per wk, 3; 30 g once every 1 ~ 2 months, 4 yrs			PBD, stage T2	Good health over 9 years
	Radiation therapy before, Vc	1	15 g twice per wk, 2; 15 g once to twice per wk, 7; 15 g once every 2–3 months, 1 yr			B-cell lymphoma stage III	Normal health over 10 years
Riordan et al., 2005	Chemotherapy before, Vc	24	150–710 mg /kg/day, 2	$Not accurate	Pilot study	Terminal cancer patients*	Progressive or stable Safe, minor side effects

PAD, Pancreatic ductal adenocarcinoma; GBM, glioblastoma; PFS, mean progression-free survival; OS, overall survival; CALGB, carboplatin + paclitaxel; NSCLC, Non-small-cell lung carcinoma; Cp, carboplatin; Pax, paclitaxel; ATO, Arsenic trioxide; non-APL AML, acute myeloid leukemia that excludes acute promyelocytic leukemia; CHASER, rituximab + cyclophosphamide + cytarabine + etoposide + dexamethasone; NHL, relapsed CD20-positive B-cell non-Hodgkin's lymphoma; RCC, renal cell carcinoma with lung metastasis; PBD, primary bladder tumor with multiple satellite tumors;#: most colon or rectal cancers, lung, and other cancer types; %: Urothelial, Head and neck, Sarcoma, Lymphoma, Prostate, Epidermoid, and other cancer types;

^*most colon or rectal primary tumors with metastasis; $: 2,6 dichlorophenolindophenol reduction method; Vc: Vitamin C; ↑ increase, ↓ decrease.