A 12 Week, Open Label, Phase I/IIa Study Using Apatone^® for the Treatment of Prostate Cancer Patients Who Have Failed Standard Therapy

Abstract

Purpose:To evaluate the safety and efficacy of oral Apatone ® (Vitamin C and Vitamin K 3 ) administration in the treatment of prostate cancer in patients who failed standard therapy. Materials and Methods: Seventeen patients with 2 successive rises in PSA after failure of standard local therapy were treated with (5,000 mg of VC and 50 mg of VK 3 each day) for a period of 12 weeks. Prostate Specific Antigen (PSA) levels, PSA velocity (PSAV) and PSA doubling times (PSADT) were calculated before and during treatment at 6 week intervals. Following the initial 12 week trial, 15 of 17 patients opted to continue treatment for an additional period ranging from 6 to 24 months. PSA values were followed for these patients. Results: At the conclusion of the 12 week treatment period, PSAV decreased and PSADT increased in 13 of 17 patients (p ≤ 0.05). There were no dose-limiting adverse effects. Of the 15 patients who continued on Apatone after 12 weeks, only 1 death occurred after 14 months of treatment. Conclusion: Apatone showed promise in delaying biochemical progression in this group of end stage prostate cancer patients.

α-Tocopheryl succinate promotes selective cell death induced by vitamin K3 in combination with ascorbate

“…An antagonistic interaction was found for the combination of a-TOS and VK3, whereas AA did not exert any effect when combined with a-TOS. As previously described (De Loecker et al, 1993;Jamison et al, 1996;Verrax et al, 2005;Tareen et al, 2008;Beck et al, 2009) and also observed in this study, an efficient synergistic effect on cell viability was observed for the pro-oxidant mixture containing pharmacological doses of AA and a redox-active compound such as menadione (VK3), (c.f. Figure 2).…”

“…with the DU145 prostate cancer cells and significantly reduced the growth rate of solid tumours without inducing any significant bone marrow toxicity and pathological changes of non-tumour tissues . Further, the safety and efficacy of oral Apatone supplementation were demonstrated in patients with prostate cancer resilient to standard therapy (Tareen et al, 2008). However, the potential long-term effect of Apatone on the disease progression and possible secondary side-effects are not known and remain to be investigated.…”

“…The combined action of ascorbic acid (AA) and vitamin K3 (VK3) has been reported to synergistically induce cell death in different cancers (De loecker et al, 1993;Verrax et al, 2005;Tareen et al, 2008). Oxidative stress generated by the ascorbate-driven quinone redox cycling kills tumour cells by a mechanism including glycolysis inhibition, loss of calcium homoeostasis, DNA damage, and altered activity of mitogen-activated protein kinases (MAPK).…”

“…In this case, cell death involves necrosis rather than apoptosis or macroautophagy (Beck et al, 2009). Pharmacological doses of AA (40.2 mM) are required to induce oxidation-dependent cytotoxicity both in vitro (Beck et al, 2009) and in vivo (Tareen et al, 2008). Cells convert ascorbate to the ascorbyl radical (A À ) with concomitant formation of H 2 O 2 in extracellular fluids (Chen et al, 2007), resulting in toxicity towards tumour cells (Rhee, 2006).…”

Changes in the rate of PSA progression and the level of alkaline phosphatase during high dose vitamin C treatment of patients with prostate cancer

“…Several studies show prostate tumor cells in vitro, in addition to implanted prostate tumors in animals, are sensitive to ascorbate [31][32][33][34]. Moreover, a clinical study combining vitamin C and vitamin K3 in prostate cancer patients who failed standard therapy showed promise in delaying biochemical progression, as measured by decreases in PSA velocity and doubling time [35].…”