Suppression of Alkaline Phosphatase in Prostate Cancer Patients by High Dose Intravenous Vitamin C Treatment: Three Cases

Background: Intravenous vitamin C (IVC) may have anti-cancer and anti-inflammatory properties. Many studies have demonstrated that IVC has a good safety profile, and can improve the quality of life of cancer patients. IVC has been proposed as an adjuvant treatment for cancer in conjunction with other therapies. Design: A retrospective study was conducted using clinical data from the Riordan Clinic (Wichita, KS) database. We collected data, when available, on the following patient characteristics at diagnosis and during the courses of IVC therapy: age, tumor stage, Gleason score, serum prostate specific antigen (PSA) and alkaline phosphatase (ALP) levels, and location of metastases. The study was conducted under the Institutional Review Board Approval of the Riordan Clinic. Demographics were limited to ensure patient confidentiality. Results: Tracking the changes in PSA and ALP in patients for whom data was available indicated that the level of ALP correlated with the presence of metastasis in our patient group. In the few cases where we found both PSA and ALP measurements, these variables tended to track each other and decrease during IVC therapy. The reductions in PSA and/or ALP concentrations (or their stabilization) were reversed once treatment stopped. Conclusion: Further research into the use of IVC in prostate cancer patients is warranted. Introduction Like most other solid malignancies, prostate cancer can metastasize to distant organs such as the liver, lungs and brain, but has much stronger affinity for the bones. In prostate cancer metastasis to bone is the main cause of death. In autopsy studies, more than 80% of the men who had died from prostate cancer possessed bone metastases (Jin, Dayyani & Gallick, 2011; Bubendorf, Schopfer, Wagner, et al., 2000). In patients with localized prostate cancer, the 5-year survival approximates 100%; however, in patients in whom distant metastases have occurred, the 5-year survival drops to 31% (Jemal, Siegel, Xu, & Ward, 2010). Bone metastases from prostate cancer are characterized by both excessive bone formation and resorption due to the increased number and activity of osteoblasts and osteoclasts (Cook, Coleman, Brown, et al., 2006). When metastatic cancer cells grow in the bone, they also produce many of the growth factors, resulting in stimulation of proliferation and maturation of osteoblasts and osteoclasts that, in turn, produce or release growth factors that further stimulate metastatic growth. One of the markers that partly reflects the osteoblastic activity is total serum alkaline phosphatase (ALP), which is most often used for indicating bone formation (Brown, Cook, Major, et al., 2005). Although serum ALP is a relatively nonspecific biomarker, patients with bone metastasis and an elevated baseline ALP are likely to have bone as the dominant source of ALP (Sonpavde, Pond, Berry, et al., 2012). ALP measurements can be used alongside bone scintigraphy in the diagnosis and follow-up of bone metastases in patients with prostate cancer (Morote, Lorente & Encabo, 1996; Wymenga, Boomsma, Groenier, et al., 2001). Moreover, as was shown in large multivariate analyses of patients with metastatic androgen-independent prostate cancer, elevated levels of serum total ALP, were independently associated with shorter survival and were predictors of early death (Smaletz, Scher, Small, et al., 2002; Halabi, Lin, Kelly, et al., 2014; Ramankulov, Lein, Kristiansen, et al., 2007; Johansen, Brasso, Iversen, et al., 2007; Robinson, Sandblom, Johansson, et al., 2008). Assessment of ALP levels before and during prostate cancer treatment might provide useful prognostic information and indicate the efficacy of treatment on the suppression of bone metastasis. Most current treatments for individuals with bone metastases have only palliative effects, with little effect on long-term survival (Costa, & Major, 2009; Lee, Saylor, & Smith, 2011). The main treatment at this stage is castration, either surgical or medical, ending the patients’ testosterone production and causing a temporary regression in disease activity. Eventually, the cancer will progress, usually within two years. In our study, we investigated the effect of high dose intravenous vitamin C (IVC) on the marker of the osteoclast activity, i.e., ALP, in several patients treated at the Riordan Clinic for whom the detailed data was available. We found that IVC provided a benefit to patients with metastatic prostate cancer by suppression of ALP levels.