Salud, Ciencia y Tecnologia, 2024; 4:699 sss, coven oi 10.5€294/ sade y2024699 a CASE REPORT ® Case Report: Compassionate application of chlorine dioxide-based solution in a patient with metastatic prostate cancer Caso clinico: Aplicacién compasiva de una solucién a base de diéxido de cloro en un paciente con cancer de préstata metastasico ‘Manuel Aparicio-Alonso' ® 1, Verénica Torres-Solérzano? = ‘Centro Médico Jurca, Medical Direction and Healthcare Responsibility Querétara, México "Universidad Auténoma de Querétaro, Unit for Basic and Applied Microbiology. Querétaro, México. Cite as: Aparcio-AlonsoM, Torres-Solérzano V Case Report: Compassionate application of chlorine dioxide-besed solution ina patient with metastatic prostate cancer . Salud, Ciencia y Tecnologia. 2024; 4:699. https://do.org/10.56294/saludcyt2024689 Submitted: 26-08-2023, Revised: 31-10-2023 Accepted: 0201-2024 Published: 02-07-2024 Editor: Prof. De. Javier Gonzalez Argote © ABSTRACT Chlorine dioxide is a powerful and cost-effective oxidizing agent that has demonstrated anti-cancer activity both in vitro and in vivo. Its proposed mechanism involves the release of free radicals, which disrupt the delicate oxidative balance within cancer cells, In case report, the patient has voluntarily opted for com- passionate chlorine dioxide therapy over continuing conventional chemotherapy and immunotherapy due to side effects and uncertain survival outcomes. The concentration of the chlorine dioxide solution was 1/100 times lower than the LOAEL threshold, ensuring that not compromise the patients’ health. This is the first follow-up in patient diagnosed with metastatic prostate cancer, who shown tumor reduction at distant sites from the primary tumor with no side effects. This preliminary observation suggests that chlorine dioxide and its free radicals could be potential mediators of an anticancer response. However, itis imperative to empha- size the importance of conducting rigorous clinical trials to validate these initial findings. Keywords: Chlorine Dioxide Solution; Cancer; Reactive Oxygen Species; Case Report. RESUMEN El didxido de cloro es un agente oxidante potente y asequible que ha demostrado actividad anticancerigena tanto in vitro como in vivo. Su mecanismo propuesto esta relacionado con la liberacion de radicales libres, que alteran el delicado equilibrio oxidativo de las células cancerosas. En este caso clinica, un paciente eli- 836 voluntariamente la terapia compasiva con diéxido de cloro frente a la quimioterapia e inmunoterapia convencionales, debido a los efectos secundarios y la incertidumbre sobre el pronéstico de supervivencia. La concentractén de la solucién de didxido de cloro fue 1/100 veces inferior al umbral LOAEL, lo que aseguré ‘no comprometer la salud del paciente. Es el primer seguimiento en un paciente diagnosticado con cancer de préstata metastésico, que mostré una reduccién de la tumoracién en lugares distantes del tumor primario sin efectos secundarios. Esta observacién preliminar sugiere que el diGxido de cloro y sus radicales libres podrian ser mediadores potenciales de una respuesta anticancerigena. Sin embargo, es imprescindible destacar la importancia de realizar ensayos clinicos rigurosos para validar estos hallazgos iniciales. Palabras clave: Solucién de Didxido de Cloro; Cancer; Especies Reactivas de Oxigeno; Caso Clinico. INTRODUCTION Chlorine dioxide solution (CDS) is a potent oxidant and a prodrug of HOCI that is widely used as a biocide. "'CDS has cytotoxic effects on cancer cells.® The cytotoxicity of CDS on cancer cells appears to be associated with the induction of oxidation that disrupts the delicate and controlled redox balance of cancer cells, which (© 2024; Los autores Este es un artculo en acceso abieto, distrbuido bajo los términes de una licencia Creative Commons (https:// creativecommons.org/icenses/by/4,0) que permite el uso, distribucién y reproduccién en cualquier medio siempre que la obra original sea correctamente citadaSalud, Ciencia y Tecnologia, 202: induces apoptosis, pyknosis, and necrosis." Thus, CDS has the potential to prevent tissue invasion and cell transformation.® The cytotoxic effect of CDS was demonstrated by inhibiting the proliferation of human cancer cell lines and pancreatic adenocarcinoma.) CDS does not appear to be toxic to normal cells, and it was shown that CDS does not have an apoptotic effect ‘on human gingival fibroblasts and endothelial cells and does not decrease the viability of periodontal ligament stem cells.’ Additionally, in the public health context, the oral use of CDS has been reported as a safe and effective therapy to treat COVID-19."" Given the documentary evidence collected to date, we raised the possibility that CDS could potentially be an effective anticancer treatment. We report cases of patients with metastatic cancer treated with maximum, daily doses of 3 mg/kg (0,003 % chlorine dioxide) given orally, enema, and/or intravenously." CASE REPORT ‘Metastatic prostate cancer In October 2019, a 64-year-old Mexican male patient with no relevant medical history underwent a routine prostate examination, which revealed abnormal prostate antigen values (> 10 ng/ml). Urinary and semen bleeding occurred promptly and was diagnosed by a biopsy of the prostate and positron emission tomography as metastatic prostate cancer. In February 2020, the patient refused chemotherapy and immunotherapy to choose metabolic therapy that consisted of 2,5 months of daily intravenous administration of the glucose analogue 2-deaxy-D-glucose (20G). Additionally, the patient followed a ketogenic diet and 20 h of intermittent fasting. During therapy, the patient did not have significant side effects. in March 2020, the patient started the oral CDS protocol by adding 1 ml of vehicle dimethyl sulfoxide (DMSO) 70% to the solution and the enema CDS protocol by absorption. In 2021, the patient added 5 g of clinoptilolite zeolite to the diet during fasting and before each meal. In 2022, the patient balanced oral and enema therapy with the intravenous CDS protocol, which the patient administered monthly according to previously described doses. Currently, the patient is without deficits or alterations in the daily routine. The patient had normal (> 4 ng/ ml) prostate antigen values and maintained periodic control, with a forty-four-month follow-up from diagnosis, (Figure 1). DISCUSSION When metastatic cancer patient pondered the risks and benefits of continued first-line treatment, by personal decision, he decided to suspend and started CDS protocols. This article describes the clinical course of the use of chlorine dioxide as part of second-line treatment. The patient with metastatic prostate cancer started his therapy with the temporary administration of 20G. In transformed cells, 20G 1s a nonmetabotizable glucose analogue that interferes with glycolysis and induces apoptosis by promoting the expression of stress-related genes." Treatment continued with oral CDS in combination with DMSO. DMSO has anti-inflammatory, analgesic and membrane-penetrating effects, and its primary use is as a vehicle for other co-administered agents.'"” Oral CDS therapy was supplemented with enemas and intravenous administration of CDS. Rectal administration has local and systemic effects, ‘it has been described as a stable route due to gastric pH elution and hepatic first pass." Additionally, possible systemic absorption via lymph nodes has been reported." Likewise, the therapy was supplemented with intravenous chlorine dioxide therapy due to full availability in the bloodstream." We suggest that multiple administration routes increased the range of action of chlorine dioxide throughout the system. CDS therapy was supplemented with clinoptilolite zeolite, which has been reported to have an anticancer cffect.’'4 This suggests that the induction of multiple redox changes may have a relevant role in destabilizing the intracellular environment of cancer cells, thus interfering with the Warburg effect phenotype. Additionally, intermittent fasting, a type of caloric restriction without malnutrition, was carried out, which promotes anticancer adaptations." This suggests that the combination of chlorine dioxide with other therapeutic agents exhibits a synergistic anticancer effect, to this case and the following cases that share the same therapeutic. approach. Images confirm the diagnosis of metastatic cancer (A, B). Images after CDS treatment (C, D), an important reduction in bone metastasis is observed. CONCLUSION The treatment with CDS protocols showed a consistent and clinically significant anticancer response, with no associated side effects. Chlorine dioxide-based treatment is safe and cost-effective. However, controlled clinical studies are proposed to determine the efficacy of the administration of CDS protocols. in addition, the question of long-term efficacy and toxicity in patients undergoing anticancer treatment is open. etps//dl.org/10.56294/saludeyt20246993. Aparicio-Alonso M, et al Figure 1. Positron emission tomography of a male patient with metastatic prostate cancer REFERENCES 1. Ning P, Shan D, Hong E, Liu L, Zhu Y, Cui R, et al. Disinfection performance of chlorine dioxide gas at ultra-low concentrations and the decay rules under different environmental factors. J Air Waste Manage Assoc. 2020;70:721-8. 2. Ma JW, Huang BS, Hsu CW, Peng CW, Cheng ML, Kao JY, et al. Efficacy and Safety Evaluation of a Chlorine Dioxide Solution. int J Environ Res Public Health, 2017;14:329. 3. Kim Y, Kumar S, Cheon W, EoH, Kwon H, Jeon Y, etal. 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Advances in rectal drug delivery systems. Pharm Dev Technol. 2018;23:942-52. 14, Katic M. Aclinoptilolite effect on cell media and the consequent effects on tumor cells in vitro. Frontiers in Bioscience. 2006;11:1722. 15. Clifton KK, Ma CX, Fontana L, Peterson LL. Intermittent fasting in the prevention and treatment of cancer. CACancer J Clin, 2021;71:527-46. FINANCING. No financing. CONFLICT OF INTEREST The authors declare that there is no conflict of interest. AUTHORSHIP CONTRIBUTION Conceptualization: Manuel Aparicio-Alonso. Data curation: Verénica Torres-Solérzano. Formal analysis: Verénica Torres-Solérzano. Investigation: Manuel Aparicio-Alonso and Verénica Torres-Solérzano, ‘Methodology: Manuel Aparicio-Alonso. Project administration: Manuel Aparicio-Alonso. Supervision: Manuel Aparicio: Alonso. Validation: Manuel Aparicio-Alonso. Visualization: Manuel Aparicio: Alonso. Writing - original draft: Verénica Torres-Sol6rzano. Writing - review and editing: Manuel Aparicio-Alonso and Verénica Torres:Solérzano. etps//dl.org/10.56294/saludeyt2024699