Open Access Journal Volume: 1.

International Journal of Immunology and Immunobiology

Preliminary Results of Oxygen-ozone Therapy as Support and Palliative Therapy in Cancer
Patients with Fatigue

Umberto Tirelli*
Cinzia Cirrito *Tumor Center, CFS, Fibromyalgia and Oxygen Ozone Therapy Unit, MEDE Clinic, Sacile (Porde-
Martina Pavanello none), Italy °National Cancer Institute, Aviano, Italy
Massiliano Berretta

Abstract Article Information

All cancer treatments may cause fatigue and it is hypothesized that the cause is tissue
damage, or the accumulation of products derived from dead cells. DOI: 10.31021/ijii.20181101
From February 2016 to December 2017 we have studied 36 patients with cancer and
Article Type: Research Article
fatigue (10 with breast cancer, 7 with lung cancer, 7 with colon cancer, 5 with renal cancer, 3
with prostate cancer, 2 with melanoma and 2 hepatocellular carcinoma). Of the 36 patients Journal Type: Open Access
treated, 10 were during neoplastic treatment, 10 had already finished the cancer therapy Volume: 1 Issue: 1
and 16 were in a palliative setting. To assess the extent of fatigue in patients we used the
Fatigue Severity Scale, which is used to estimate the severity of the symptom with a score Manuscript ID: IJII-1-101
from 1 to 7. Patients were treated with auto hemo transfusion (GAE) according to the SIOOT Publisher: Boffin Access Limited
(Scientific Society of Oxygen Ozone Therapy) protocols, twice a week for one month and
twice a month as maintenance therapy. No side effects have been found, and 26 patients
(72%) achieved a significant improvement (>50% of the symptoms). Received Date: 19 Febraury, 2018
Ozone therapy is a valid supportive therapy for fatigue in patients with cancer, both Accepted Date: 07 March, 2018
during cancer therapy and in a palliative setting without any significant side effects.
Published Date: 14 March, 2018
Introduction
Ozone, a gas discovered in the mid-nineteenth century, is a molecule consisting of three *Corresponding author:
atoms of oxygen in a dynamically unstable structure due to the presence of mesomeric Umberto Tirelli
states. The gas is colorless, acrid in odor and explosive in liquid or solid form. It has a half-
Director
life of 40 min at 20°C and about 140 min at 0°C. Its basic function is to protect humans from
Tumor Center, CFS
harmful effects of UV radiation. Ozone occurs at less than 20μg/m3 from the Earth’s surface
at concentrations that are perfectly compatible with life. Although ozone has dangerous Fibromyalgia and Oxygen Ozone Therapy Unit
effects, yet researchers believe it has many therapeutic effects [1–3]. The beginning of precise MEDE Clinic, Sacile (Pordenone)
medical ozone generators has only recently allowed the mechanisms, action and possible Italy
toxicity of ozone to be evaluated by clinical trials [2]. Ozone has a capacity to oxidize organic Tel: 3484406851
compounds, [4] and has well-known toxic effects on the respiratory tract when present in E-mail: utirelli@cro.it
smog [5–6]. In medical use the gas produced from medical grade oxygen is administered
in precise therapeutic doses, and never via inhalation, and advocates that it has excellent
health benefits in dental caries, decrease blood cholesterol and stimulation of antioxidative Citation: Tirelli U, Cirrito C, Pavanello M,
responses, modifies oxygenation in resting muscle and is used in complementary treatment Berretta M. Preliminary Results of Oxygen-ozone
of hypoxic and ischemic syndromes [7–10]. Therapy as Support and Palliative Therapy in
The National Comprehensive Cancer Network describes fatigue as a universal Cancer Patients with Fatigue. Int J Immunol
symptom present at different levels in all subjects with cancer undergoing chemotherapy, Immunobiol. 2018 Mar;1(1):101
radiotherapy, bone marrow transplantation. Among the subjects with metastases, the
prevalence reaches the 78%. Patients with cancer who are cured may report fatigue even
after the end of the therapy and according to some studies it can persist up to 5 years after Copyright: © 2018 Tirelli U, et al. This is
an open-access article distributed under the
healing [11-15].
terms of the Creative Commons Attribution 4.0
Except for situations in which fatigue is caused by chemotherapy induced anemia, international License, which permits unrestricted
in other cases the underlying pathophysiological mechanism is unknown. It seems that use, distribution, and reproduction in any
its origin is multi-factorial: on one hand the tumor and the therapy and on the other the medium, provided the original author and source
biological and genetic characteristics of each person. These are risk factors: sleeping are credited.
disorders, insufficient physical activity, chronic pain and emotional stress [16].
All cancer treatments may cause fatigue, it is hypothesized that the cause is tissue
damage, or the accumulation of products derived from dead cells. Cancer treatments also
cause pro-inflammatory cytokines formation, high in patients who accuse fatigue after
the treatment. Fatigue increases during radiotherapy and reaches its peak at about half
cycle, generally improving after two months from the end. Biotherapies expose patients to
endogenous and exogenous cytokines and cause aflu-like syndrome with symptoms such as
fatigue, fever, chills, myalgias, headaches and general malaise, but also mental fatigue and
cognitive deficits. Chemotherapy is associated with fatigue, which worsens if pain, anxiety
and depression are also present. The characteristics of patients associated with worsening

Int J Immunol Immunobiol Volume: 1.1 1

Journal Home: https://www.boffinaccess.com/journals/immunology-and-immunobiology/index.php

or remission of fatigue are not known. Overall, fatigue and pain are In our experience, ozone therapy seems to be effective either in
often associated with cancer therapies [17-19]. patients with fatigue related to antineoplastic therapy, after therapy
has been finished and also in palliative setting. Due to the overall
Materials, Methods and Results small number of patients in each group, it has not yet been evaluated
Within the Tumor Center, CFS, Fibromyalgia and Oxygen Ozone in detail the outcome in each group of patients.
Therapy Unit, MEDE Clinic, Sacile, Pordenone (Italy), we decided to In conclusion, at our knowledge, this is the largest study of
undertake a study with the aim to evaluate the efficacy of oxygen- patients with cancer treated with ozone therapy reported in the
ozone therapy on cancer patients with fatigue, either during cancer literature. Oxygen-ozone therapy seems a valid supportive therapy
therapy or after cancer therapy or in a palliative setting. The samples for fatigue in patients with cancer, both during cancer therapy and
were collected to the MEDE Clinic, Sacile (Pordenone), Italy. This in a palliative setting, without any significant side effects. We hope
retrospective work was performed in compliance with the ethical to increase the number of patients to some more different kinds of
values laid down by the Declaration of Helsinki, and informed consent cancer either in therapy of in a palliative setting.
documentation was reviewed and agreed by the independent ethics
committee at the MEDE Clinic. Differences according to age, gender, References
and adverse events have been calculated using the Chi-square test. 1. Di Paolo N, Bocci V, Gaggioti E. Ozone therapy editorialreview. Int
Univariate analyses have been performed to match the study arms J ArtificialOrgans. 2004 Mar;27(3):168–175.
and the unadjusted logic regression method has been used to assess 2. Bocci V. Biological and clinical effects of ozone: Has ozone therapy
crude odds ratios and 95% confident intervals. Logistic progression a future inz` medicine? Br J Biomed Sci. 1999;56(4):270–279.
models adjusted for major confounders like age and gender have
been used to calculate adjusted odds ratios and 95% confident ratios. 3. Bocci V. Does ozone therapy normalize the cellular redox balance?
P<0.05 has been considered statistically significant.rom February Implications for the therapy of human immunodeficiency virus
2016 to December 2017 we have included in the study 36 patients infection and several other diseases. Med Hypothesis. 1996
with cancer and fatigue, 10 with breast cancer(4 during cancer Feb;46(2):150–154.
therapy, 6 after having finished cancer therapy, all females, aged 41 4. Razumovskii Z. New York: Elsevier; 1984. Ozone and its reactions
to 72 years), 7 with lung cancer(all in a palliative setting, i.e. after with organic compounds. Available from: http://ozonicsint.com/
chemotherapy and/or radiotherapy have been used and patients articles_vivo.html.
were in progression without any potential further effective therapy 5. Health and Environmental Effects of Ground-Level Ozone. U.S.
available, 6 males and 1 female, aged 51 to 78 years), 7 with colon EPA. 1997. Jul, Available from: http://www.practicalasthma.net/
cancer(1 during chemotherapy, 3 after therapy was finished and 3 pages/topics/aaozone.htm.
in a palliative setting, 5 males and 2 females, aged 48 to 75 years), 5 6. Folinsbee LJ. Effects of ozone exposure on lung function in man.
with renal cancer(2 during cancer therapy, 1 after finishing cancer Rev Environ Health. 1981;3(3):211–240.
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 7. Bocci V. Is it true that ozone is always toxic? The end of a dogma.
to 81 years), 2 with melanoma(all in a palliative setting, both females Toxicol ApplPharmacol. 2006 Nov;216(3):493–504.
and aged 39 to 52 years) and 2 hepatocellular carcinoma(both in 8. Holmes J. Clinical reversal of root caries using ozone, double-
a palliative setting, both males, aged 61 to 71 years);therefore, of blind, randomised, controlled 18-month trial. Gerodontology.
the 36 patients treated, 10 were during neoplastic therapy, 10 had 2003 Dec;20(2):106–114.
already finished the cancer therapy and 16 were in a palliative 9. Hernández F, Menéndez S, Wong R. Decrease of blood cholesterol
setting. To assess the extent of fatigue in patients with cancer we used and stimulation of antioxidative response in cardiopathy patients
the Fatigue Severity Scale, which is used to estimate the severity of treated with endovenous ozone therapy. Free Radical Biol Med.
the symptom with a score from 1 to 7 [20]. 1995 Jul;19(1):115–119.
Patients were treated with auto hemo transfusion (GAE) 10. Clavo B, Pérez JL, López L, Suárez G, Lloret M, et al. Effect of ozone
according to the SIOOT (Scientific Society of Oxygen Ozone therapy on muscle oxygenation. J Altern Complement Med. 2003
Therapy) protocols, twice a week for one month and twice a month Apr;9(2):251–256.
as maintenance therapy. No side effects have been found, while 26 11. National Comprehensive Cancer Network. Cancer-related fatigue.
patients (72%) achieved a significant improvement(>50% of the NCCN 2014:1.
symptoms)of fatigue during therapy, or after therapy was finished,
12. Vitkauskaite E, Jouzaityte E, Drukteniene J. A sistematic review of
or in a palliative setting, without any significant difference among the
cancer related fatigue. BiologinePsichiatrijairpsichofarmakologija.
three groups of patients, also due to the small numbers of patients
2011;13(2):74-77.
in each group. Due to the short period of follow up, we did not yet
evaluate the duration of response obtained. 13. Weis J. Cancer related fatigue: prevalence, assessment and
treatment strategies. Expert Rev Pharmacoecon Outcome Res
Discussion 2011 Aug;11(4):441-446.
When a patient begins an anticancer treatment, it is very 14. Mustian KM, Sprod LK, Janelsins M, Peppone LJ, Mohile S. Exercise
important to explain that fatigue may occur. Informing the patient recommendations for cancer-related fatigue, cognitive impairment,
is the first step towards proper management. Fatigue can be treated sleep problems, depression, pain, anxiety, and physical dysfuncion:
with pharmacological and non-pharmacological interventions. It is A review. Oncol Hematol Rev. 2012;8(2):81-88.
generally recommended to use both. Pharmacological therapies vary
15. Vogelzang N, Breitbart W, Cella D, Curt GA, Groopman JE, et al. The
depending on the cause of fatigue (erythropoietin for anemia, sleep
fatigue coalition. Patient, caregiver, and oncologist perceptions of
inducers for insomnia, antidepressants for depression). Among the
cancer-related fatigue: results of a tri-part assessment survey.
non-pharmacological interventions, physical exercise seems to be the
SemHematol. 1997 Jul;34 (3 Suppl 2):4-12.
most effective [21-28].
16. Bower JE. Cancer-related fatigue--mechanisms, risk factors, and
Ozone therapy is one of the therapies that the scientific community
treatments. Nat Rev Clin Oncol. 2014 Oct;11(10):597-609.
considers as integrative but not substitutive for treatments. Regarding
tumors, ozone therapy may be used as adjuvant for palliative care. 17. Ryan JL, Carroll JK, Ryan EP, Mustian KM, Fiscella K, et al.
The procedure aims to increase oxygenation and cell metabolism and Mechanisms of cancer-related fatigue. Oncologist. 2007;12 Suppl
improve the quality of life. Ozone therapy improves oxygenation in 1:22-34.
most tumor tissues with hypoxia and can be considered a potential 18. Gomondi C, Neuenschwander H. Pathophisiology of fatigue. In
adjuvant to chemotherapy and radiotherapy [11-20]. At our textbook of palliative medicine fatigue. Eds Eduardo Bruera,
knowledge, there are few reports published in literature regarding Irene Higginson, Charles F von Gunten Textbook of Palliative
ozone therapy in cancer patients [29-31]. Medicine CRC Press 2009.

Int J Immunol Immunobiol Volume: 1.1 2/3

Journal Home: https://www.boffinaccess.com/journals/immunology-and-immunobiology/index.php

19. National Cancer Institute, Fatigue (PDQ), National Cancer (2013) Cancer-relatedfatigue in the elderly. Support Care Cancer.
Institute 2014. 2013 Oct;21(10):2899-2911.
20. Annunziata MA, Muzzatti B, Mella S, Narciso D, Giacalone 26. Giacalone A, Spina M, Berretta M, Tirelli U. Two types of fatigue in
A,Tirelli U, et al. The revised piper fatigue scale (PFS-R) cancer patients. Br J Cancer. 2012 Jan;106(2):424.
for Italiancancerpatients: a validationstudy. Tumori. 2010 27. Spazzapan S, Bearz A, Tirelli U. Fatigue in cancer patients
Apr;96(2):276-281. receiving chemotherapy: an analysis of published studies. Ann
21. Arpino C, Carrieri MP, Valesini G, Pizzigallo E, Tirelli U, et Oncol. 2004 Oct;15(10):1576.
al. Idiopathicchronicfatigue and chronicfatiguesyndrome: 28. Tavio M, Milan I, Tirelli U. Cancer-relatedfatigue (review). Int J
a comparison of two case-definitions. AnnIst Super Sanita. Oncol. 2002 Nov;21(5):1093-1099.
1999;35(3):435-441.
29. Clavo B, Santana-Rodriguez N, Llontop P, Gutierrez D, Ceballos D,
22. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, et al. The et al. Ozone Therapy in the Management of Persistent Radiation-
chronic fatigue syndrome: a comprehensive approach to its Induced Rectal Bleeding in Prostate Cancer Patients. Evid Based
definition and study. International Chronic Fatigue Syndrome Complement Alternat Med. 2015;2015:480369.
Study Group. Ann Intern Med. 1994 Dec;121(2):953-959.
30. Velikaya VV, Gribova OV, Musabaeva LI, StartsevaZhA, Simonov
23. Giacalone A, Berretta M, Spina M, Tirelli U. Is long-term fatigue in KA, et al.[Ozone therapy for radiation reactions and skin lesions
patients with cancer an infrequent symptom? J Clin Oncol. 2012 after neutron therapy in patients with malignant tumors]. Vopr
Nov;30(33):4175. Onkol. 2015;61(4):571-574.
24. Giacalone A, Polesel J, De Paoli A, Colussi AM, Sartor I, et al. 31. Clavo B, Santana-Rodriguez N, López-Silva SM, Dominguez E, Mori
Assessing cancer-related fatigue: the psychometric properties M, Gutierrez D, et al. Persistent PORT-A-CATH®-related fistula and
of the Revised Piper Fatigue Scale in Italian cancer inpatients. fibrosis in a breast cancer patient successfully treated with local
Support Care Cancer. 2010 Sep;18(9):1191-1197. ozone application.J Pain Symptom Manage. 2012 Feb;43(2):e3-6.
25. Giacalone A, Quitadamo D, Zanet E, Berretta M, Spina M, Tirelli U.

Int J Immunol Immunobiol Volume: 1.1 3/3