-
Oxygen-ozone therapy as support and palliative therapy in 50 cancer patients with fatigue - A short report
Abstract. –
OBJECTIVE: Fatigue may be cause by all cancer treatments, maybe because the tissue damage or the build-up of dead cells derived products.
Corresponding Author: Umberto Tirelli, MD; e-mail: utirelli@cro.it
PATIENTS AND METHODS:
At the Mede Clinic in Sacile, Pordenone, Italy, from February 2016 to May 2018 we studied 50 patients with cancer and fatigue (15 with breast cancer, 12 with lung cancer, 11 with colon cancer, 5 with renal cancer, 3 with prostate cancer, 2 with melanoma and 2 hepatocellular carcinoma). Patients were treated with Auto Hemotransfusion (GAE) according to the SIOOT (Scientific Society of Oxygen Ozone Therapy) protocols, two times a week for one month and then twice monthly as maintenance therapy. RESULTS: Nineteen of them were undergoing neoplastic treatment, 10 had already ended the cancer therapy and 21 were in a palliative setting. The Fatigue Severity Scale was used to assess the extent of fatigue in patients, in order to estimate the severity of the symptom with a score from 1 to 7. No side effects were found, and 35 patients (70%) achieved a significant improvement (> 50%) of the symptoms. CONCLUSIONS: Our preliminary data demonstrate that ozone therapy is a valid supportive therapy for fatigue in cancer patients, both during cancer therapy and in a palliative setting with no significant side effects.
Key Words Cancer, Fatigue, Ozono therapy.
Introduction
Ozone is a gas discovered in the mid-1800; its molecule consists in three atoms of oxygen in a dynamically unstable structure due to the presence of mesomeric states. Ozone is colorless, has an acrid smell and is explosive in its liquid or solid forms. Its half-life is 40 min at 20°C and about 140 min at 0°C. Its basic function is to protect humans from harmful effects of UV radiation. Ozone occurs at less than 20 μg/m3 from the Earth’s surface, at concentrations that are perfectly compatible with life. Despite ozone has hazardous effects, researchers believe it has many therapeutic effects1-3. The development of accurate medical ozone generators has recently allowed the evaluation of mechanisms, action and possible toxicity of ozone in clinical trials2. Ozone is capable to oxidize organic compounds4, and has well-known poisonous effects on the re-spiratory tract when present in smog5,6. In medi-cal use ozone derived from medical grade oxygen is administered in precise therapeutic doses, but never through inhalation, and advocates that it has exceptional health benefits in dental caries, decrease blood cholesterol and stimulation of antioxidative responses, modifies oxygenation in resting muscle and is used in complementary treatment of hypoxic and ischemic syndromes7-10. The National Comprehensive Cancer Network has described fatigue as a general sign present at different levels in all cancer patients undergoing chemotherapy (AC), radiotherapy, or bone mar-row transplantation. Among the subjects with metastases, the prevalence can be up to 78%. Patients with cancer who are healed, may report fatigue even after the end of treatments and ac-cording to some studies, it can persist up to 5 years after they have been cured11-15. Apart from fatigue caused by chemotherapy-induced anemia, in other cases the underlying pathophysiological mechanism is unknown. It seems that fatigue or-igin is multi-factorial: the tumor and the therapy on one hand and the biological and genetic char-acteristics of each person on the other. Sleeping disorders, insufficient physical activity, chronic pain and emotional stress are risk factors16. All cancer treatments may cause fatigue, it is hy-pothesized that the reason is tissue damage, or the accumulation of products derived from dead cells. Cancer treatments also produce the pro-in-flammatory cytokines formation that is high in patients complaining for fatigue after the therapy. During radiotherapy fatigue increases, reaching its peak at about half cycle, but generally im-proving after two months from the conclusion of treatments. Patients undergoing biotherapies are expose to endogenous and exogenous cytokines causing a flu-like syndrome with symptoms such as fatigue, fever, chills, myalgia, headaches and general malaise, but also mental fatigue and cognitive deficits. Antiblastic chemotherapy is associated with fatigue, worsening when pain, anxiety or depression are concomitant. Still un-known are the characteristics of patients asso-ciated with worsening or remission of fatigue. Overall, fatigue and pain are often associated with cancer therapies17-19.
Patients and Methods
In order to evaluate the efficacy of oxy-gen-ozone therapy on cancer patients with fa-tigue, either during or after cancer therapy or in a palliative setting, we decided to undertake a study collecting the samples at the Tumor Center, CFS, Fibromyalgia and Oxygen Ozone Therapy Unit, Mede Clinic, Sacile (Pordenone, Italy). This work has been performed in compliance with the ethical values laid down by the Declaration of Helsinki, and informed consent documentation have been reviewed and agreed by the indepen-dent Ethics Committee at the Mede Clinic.
Statistical Analysis
The x2 test has been used to calculate the differ-ences according to age, gender, and adverse events. Univariate analyses have been performed to match the study arms and the unadjusted logic regression method has been used to assess crude odds ratios and 95% confident intervals. Logistic progression models adjusted for major confounders like gender and age have been used to calculate adjusted odds ratios and 95% confident ratios; p<0.05 has been considered statistically significant.
Results
Between February 2016 to May 2018 we have enrolled in the study 50 consecutive patients with cancer and fatigue, 15 with breast cancer (9 during cancer therapy, 6 after having finished cancer therapy, all females, aged 38 to 72 years), 12 with lung cancer (all in a palliative setting, i.e. after AC and/or radiotherapy have been used and patients were in progression without any potential further effective therapy available, 10 males and 2 female, aged 50 to 78 years), 11 with colon cancer (5 during AC, 3 after therapy was fin-ished and 3 in a palliative setting, 7 males and 4 females, aged 48 to 78 years), 5 with renal cancer (2 during cancer therapy, 1 after finishing cancer therapy and 2 in a palliative setting, 3 males and 2 females, aged 41 to 68 years), 3 with prostate cancer (all during cancer therapy, aged 60 to 81 years), 2 with melanoma (all in a palliative set-ting, both females and aged 39 to 52 years) and 2 hepatocellular carcinoma (both in a palliative setting, both males, aged 61 to 71 years). There-fore, of the 50 patients treated, 19 were during AC, 10 had already finished the cancer therapy and 21 were in a palliative setting (Table I). To assess the extent of fatigue in patients with cancer we have used the Fatigue Severity Scale, in order to estimate the severity of the symptom with a score from 1 to 720. Patients have been treated with auto hemotransfusion (GAE) according to the Scientific Society of Oxygen Ozone Therapy (SIOOT) protocols, twice a week for one month and then twice a month as maintenance therapy. No significant side effects have been found, while 35 patients (70%) achieved a significant improve-ment (>50% of the symptoms) of fatigue during therapy, after therapy was terminated, or in a pal-liative setting, without any significant difference among the three groups of patients, also due to the small numbers of patients in each group. Be-cause the short period of follow up, we have not yet evaluate the duration of response obtained.
-
Table I. Characteristics of 35/50 pts who responded to ozone therapy.
-
Discussion
When a patient begins an anticancer treatment, it is very important to explain that fatigue may occur. Informing the patient is the first step to-wards a proper management. Fatigue can be treat-ed with pharmacological and non-pharmacological interventions. It is generally recommended to use both. Pharmacological therapies differ depending on the cause of fatigue (erythropoietin for ane-mia, sleep inducers for insomnia, antidepressants for depression). Among the non-pharmacological interventions, physical exercise seems to be the most effective24-31. The scientific community con-siders ozone therapy among the integrative but not substitutive for treatments. Ozone therapy may be used as adjuvant for palliative care in tumors. The procedure aims to increase oxygenation and cell metabolism and improve the quality of life Ozone therapy improves oxygenation in most tumor tis-sues with hypoxia and it may be considered a potential adjuvant to AC and radiotherapy11-20. At our knowledge, there are few reports published in literature regarding ozone therapy in cancer pa-tients21-23. In our case series, ozone therapy seems to be effective either in patients with fatigue relat-ed to antineoplastic therapy, after therapy has been finished and also in palliative setting. Due to the overall small number of patients in each group, it has not yet been evaluated in detail the outcome in each group of patients.
Conclusions
At our knowledge, this is among the largest studies reported in the literature of cancer pa-tients treated with oxygen-ozone therapy. Oxy-gen-ozone therapy seems to be a valid supportive therapy for fatigue in cancer patients, both during cancer therapy and in a palliative setting, without any significant side effects. In the next future we hope to increase the number of patients to some more different kinds of cancer either in therapy of in a palliative setting and in a vision of com-plementary and integrative medicine32,33. Consid-ering the small number of patients treated and evaluated we firmly believe that others confirma-tory randomized trial are needed to improve the amount of data and quality of scientific results.
Conflict of Interests
The Authors declare that they have no conflict of interests.
References
1) Di Paolo N, Bocci V, Gaggioti E. Ozone therapy editorial review. Int J Artificial Organs 2004; 27: 168-175.
2) Bocci V. Biological and clinical effects of ozone: has ozone therapy a future in medicine? Br J Biomed Sci 1999; 56: 270-279.
3) Bocci V. Does ozone therapy normalize the cellular redox balance? Implications for the therapy of human immunodeficiency virus infection and several other diseases. Med Hypothesis 1996; 46: 150-154.
4) Razumovskii Z. New York: Elsevier; 1984. Ozone and its reactions with organic compounds. Available from: http://ozonicsint.com/articles_vivo.html
5) Health and environmental effects of ground-level ozone. U.S. EPA. 1997. Jul, Available from: http:// www.practicalasthma.net/pages/topics/aaozone.Htm
6) Folinsbee LJ. Effects of ozone exposure on lung function in man. Rev Environ Health 1981; 3: 211-240.
7) Bocci V. Is it true that ozone is always toxic? The end of a dogma. Toxicol Appl Pharmacol 2006; 16: 493-504.
8) Holmes J. Clinical reversal of root caries using ozone, double-blind, randomised, controlled 18-month trial. Gerodontology 2003; 20: 106-114.
9) Wu MY, Xing CY, Wang JN, Li Y, Lin XW, Fu ZJ. Therapeutic dosage of ozone inhibits autophagy and apoptosis of nerve roots in a chemically induced radiculoneuritis rat model. Eur Rev Med Pharmacol Sci 2018; 22: 1787-1797.
10) Clavo B, Pérez JL, López L, Suárez G, Lloret M, Rodríguez V, Macías D, Santana M, Morera J, Fiuza D, Robaina F, Günderoth M. Effect of ozone therapy on muscle oxygenation. J Altern Complement Med 2003; 9: 251-256.
11) National Comprehensive Cancer Network. Cancer-related fatigue. NCCN 2014: 1.
12) Vitkauskaitė E, Juozaitytė E, Druktenienė J, Bunevičiu Rs. A systematic review of cancer related fatigue. Biological Psychiatry and Psychopharmacology 2011; 2: 74-77.
13) Weis J. Cancer related fatigue: prevalence, assessment and treatment strategies. Expert Rev Pharmacoecon Outcome Res 2011; 11: 441-446.
14) Mustian KM, Sprod LK, Janelsins M, Peppone LJ, Mohile S. Exercise recommendations for cancer-related fatigue, cognitive impairment, sleep problems, depression, pain, anxiety, and physical dysfuncion: a review. Oncol Hematol Rev 2012; 8: 81-88.
15) Vogelzang N, Breitbart W, Cella D, Curt GA, Groopman JE, Horning SJ, Itri LM, Johnson DH, Scherr SL, Portenoy RK. The fatigue coalition. Patient, caregiver, and oncologist perceptions of cancer-related fatigue: results of a tri-part assessment survey. SemHematol 1997; 34: 4-12.
16) Bower JE. Cancer-related fatigue--mechanisms, risk factors, and treatments. Nat Rev Clin Oncol. 2014; 11: 597-609.
17) Ryan JL, Carroll JK, Ryan EP, Mustian KM, Fiscella K, Morrow GR. Mechanisms of cancer-related fatigue. Oncologist 2007; 12 Suppl 1: 22-34.
18) Gomondi C, Neuenschwander H. Pathophisiology of fatigue. In textbook of palliative medicine fatigue. Editors Eduardo Bruera, Irene Higginson, Charles F von Gunten. Textbook of Palliative Medicine, CRC Press, 2009.
19) National Cancer Institute, Fatigue (PDQ), National Cancer Institute 2014.
20) Annunziata MA, Muzzatti B, Mella S, Narciso D, Giacalone A, Fratino L, Tirelli U. The revised piper fatigue scale (PFS-R) for Italian cancer patients: a validation study. Tumori 2010; 96: 276-281.
21) Clavo B, Santana-Rodriguez N, Llontop P, Gutierrez D, Ceballos D, Méndez C, Rovira G, Suarez G, Rey-Baltar D, Garcia-Cabrera L, Martínez-Sánchez G, Fiuza D. Ozone therapy in the management of persistent radiation-induced rectal bleeding in prostate cancer patients. Evid Based Complement Alternat Med 2015; 2015: 480369.
22) Velikaya VV, Gribova OV, Musabaeva LI, Startseva Zh A, Simonov KA, Aleinik AN, Lisin VA. [Ozone therapy for radiation reactions and skin lesions after neutron therapy in patients with malignant tumors]. Vopr Onkol 2015; 61: 571-574.
23) Clavo B, Santana-Rodriguez N, López-Silva SM, Dominguez E, Mori M, Gutierrez D, Hernandez MA, Robaina F. Persistent PORT-A-CATH®-related fistula and fibrosis in a breast cancer patient successfully treated with local ozone application. J Pain Symptom Manage 2012; 43: e3-e6.
24) Arpino C, Carrieri MP, Valesini G, Pizzigallo E, Rovere P, Tirelli U, Conti F, Dialmi P, Barberio A, Rusconi N, Bosco O, Lazzarin A, Saracco A, Moro ML, Vlahov D. Idiopathicchronicfatigue and chronicfatiguesyndrome: a comparison of two case-definitions. Ann Ist Super Sanità 1999; 35: 435-441.
25) Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A, Schluederberg A, Jones JF, Lloyd AR, Wessely S, Gantz NM, Holmes GP, Buchwald D, Abbey S, Rest J, Levy JA., Jolson H, Peterson DL, Vercoulen JHMM, Tirelli U, Evengard B, Natelson BH, Steele L, Reyes M, and Reeves WC. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med 1994; 15: 953-959.
26) Giacalone A, Berretta M, Spina M, Tirelli U. Is longterm fatigue in patients with cancer an infrequent symptom? J Clin Oncol 2012; 30: 4175;
27) Giacalone A, Polesel J, De Paoli A, Colussi AM, Sartor I, Talamini R, Tirelli U. Assessing cancer-related fatigue: the psychometric properties of the Revised Piper Fatigue Scale in Italian cancer inpatients. Support Care Cancer 2010; 18: 1191- 1197.
28) Giacalone A, Quitadamo D, Zanet E, Berretta M, Spina M, Tirelli U. Cancer-related fatigue in the elderly. Support Care Cancer 2013; 21: 2899-2911.
29) Giacalone A, Spina M, Berretta M, Tirelli U. Two types of fatigue in cancer patients. Br J Cancer 2012; 106: 424.
30) Spazzapan S, Bearz A, Tirelli U. Fatigue in cancer patients receiving chemotherapy: an analysis of published studies. Ann Oncol 2004; 15: 1576.
31) Tavio M, Milan I, Tirelli U. Cancer-related fatigue (review). Int J Oncol 2002; 21: 1093-1099.
32) Berretta M, Della Pepa C, Tralongo P, Fulvi A, Martellotta F, Lleshi A, Nasti G, Fisichella R, Romano C, De Divitiis C, Taibi R, Fiorica F, Di Francia R, Di Mari A, Del Pup L, Crispo A, De Paoli P, Santorelli A, Quagliariello V, Iaffaioli RV, Tirelli U, Facchini G. Use of Complementary and Alternative Medicine (CAM) in cancer patients: an Italian multicenter survey. Oncotarget 2017; 8: 24401-24414.
33) Del Buono A, D’orta A, Tarro G, Rossi P, Papa S, Iodice L, Abbadessa A, Montano L, Portale G, Berretta M, Di Francia R. “Terra dei fuochi, the starting point”. The role of prevention and complementary medicine in the clinical practice. WCRJ 2018; 5: e1112.
-
Site Menu
Remember...
"A journey of a thousand
miles begins with a single step!"
Lao Tzu
Keep in Touch
Sign up for our newsletter and be the first to know about coupons and special promotions.
