RU2849274C1 - Use of inhalation composition to reduce organotoxicity in breast cancer patients undergoing chemotherapy - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to the use of agents to reduce organ toxicity during chemotherapy in patients with breast cancer. The use of an inhalation composition consisting of the following gases, wt.%: xenon, oxygen, as an agent for reducing organ toxicity during chemotherapy is proposed.

EFFECT: reduction of neuro- and cardiotoxicity caused by chemotherapy, as well as stabilisation of the patient's mental state and improvement of the quality of life of patients receiving aggressive cancer treatment.

1 cl, 4 tbl, 1 ex

Description

Field of technology to which the invention relates

The invention relates to medicine, namely to oncology, and in particular can be used in chemotherapy to reduce its organotoxicity.

State of the art

Breast cancer is a pressing issue in modern oncology, accounting for over 20% of all female cancer cases and steadily increasing in incidence. Including adjuvant chemotherapy in combination treatment regimens improves long-term results and outcomes in early breast cancer. A complex issue with chemotherapy is its systemic toxicity, which is associated with indiscriminate action on both tumor and healthy cells in the mitotic phase, leading to exacerbation of metabolic disorders.

The influence of xenon therapy on hematopoiesis processes is known from the prior art. Thus, according to the randomized clinical study Stoppe et al. Sub-anesthetic Xenon Increases Erythropoietin Levels in Humans: A Randomized Controlled Trial. Sports Med. 2016;46(11):1753-1766, even a single inhalation of a subanesthetic dose of xenon (30% over 45 minutes) in healthy volunteers led to a significant increase in the level of endogenous erythropoietin already 8 hours after inhalation, with a peak concentration after 24 hours. This effect is explained by the activation of the hypoxia-induced factor HIF-1α, which stimulates the expression of the erythropoietin (EPO) gene.

However, similar studies have not yet been conducted in the oncology population; this mechanism may have significant clinical implications for patients receiving myelosuppressive chemotherapy.

Furthermore, it is known from the prior art that the use of xenon can improve the psychoemotional state and overall well-being in cancer patients. For example, in a study by Rozenko D.A. et al., "Neuropsychological characteristics of reproductive-age patients diagnosed with breast cancer during surgical treatment using xenon-oxygen therapy. Research and practice in medicine. 2021; 8(3):10-20," in patients with breast cancer after mastectomy, the use of xenon inhalations (30%, 5 days) was accompanied by a decrease in anxiety and depression and a 2-2.5-fold improvement in overall well-being according to the ESAS scale, as well as an increase in physical and mental health indicators according to the MOS-SF-36 questionnaire compared to the control group.

In addition to the above, from the article by Nikolaev L. et al., Xenon as a component of support therapy during chemotherapy in patients with breast cancer. Effective pharmacotherapy. 2014; (57): 6–9, xenon is known to be used to prevent vomiting in the treatment of oncological diseases, in particular, breast cancer. In this case, therapeutic doses of medical xenon are administered by inhalation. Each chemotherapy session began with the inhalation of KseMed through a specialized xenon therapeutic circuit KTK-01. The procedure began with filling the circuit and reservoir with a xenon-oxygen mixture in a ratio of 2:3 (five-liter reservoir). Then, after several deep breaths, the patients exhaled as much as possible and began breathing through a face mask along a closed circuit, in which the xenon concentration was maintained at approximately 30%. The chemotherapy drug was administered when the xenon concentration in the oxygen-xenon mixture reached 27–30%. At the end of the procedure, the xenon supply was turned off and oxygen was administered at a flow rate of 6–8 l/min for 5–10 minutes. Any remaining anesthetic gas was removed into a xenon recycling device. Duration: 30–40 minutes. Xenon consumption: 3–3.5 liters per procedure. If nausea occurred, the procedure was repeated. During the procedure, ECG, blood pressure, pulse oximetry, and xenon and oxygen concentrations in the breathing circuit were monitored.

Thus, the analysis of the state of the art did not reveal any information about the known use of xenon, a mixture of xenon and oxygen, during chemotherapy in patients with breast cancer to ensure the elimination of organotoxicity effects.

Based on the above premises, it was suggested that the use of xenon could reduce the organotoxic effects of chemotherapeutic drugs.

The technical problem we solved was to reduce organ toxicity during high-dose adjuvant chemotherapy in patients with breast cancer.

Disclosure of the essence of the invention

The technical result achieved is a reduction in neuro- and cardiotoxicity, as well as the elimination of the negative impact of chemotherapy on the patient's mental state. Furthermore, the use of xenon improves the quality of life of patients undergoing aggressive cancer treatment.

The said technical result is achieved through the use of an inhalation composition consisting of the following gases in wt.%: xenon 25-40%, oxygen 60-75%, as a means for reducing organotoxicity in breast cancer patients undergoing high-dose adjuvant chemotherapy.

In the first days after chemotherapy, the greatest changes in organs associated with the toxic effects of chemotherapeutic drugs usually occur, which requires timely assistance to patients and is based on the following points:

a. Onset and duration of action of xenon – its clinical effects, such as sedation, appear immediately after inhalation (within minutes). Animal studies have shown that organoprotective properties are evident with both pre- and post-conditioning of xenon. The maximum effect is achieved when the first xenon inhalation is administered before chemotherapy administration – on the day of chemotherapy initiation. This ensures early intervention on the pathophysiological pathways of cellular damage and protection, i.e., preconditioning, before the chemotherapy reaches toxic concentrations.

b. Organ damage from cytostatics occurs when the free (circulating) fraction of the drug and/or its active metabolites exceed the toxicity threshold. Therefore, the inhalation course should cover: a time of ≥ 4 t₁/₂ of the drug (half-life)—then 6% or less of the initial dose remains in the blood; plus an additional 24 hours to cover the late window of cellular apoptosis/inflammation.

Regarding the safety and efficacy of xenon inhalation at a target concentration of 25-40 wt.% xenon:

1. Safety:

40% by volume corresponds to ≈0.4 MAC (minimum alveolar concentration); this dose is far from the threshold for loss of consciousness of 65-70% by volume and does not depress respiration or hemodynamics.

2. The effectiveness of xenon use is due to:

a. antiemetic effect during chemotherapy

b. severe analgesia after oncosurgery

c. neuroprotection/improvement of consciousness in patients with chronic impairment of consciousness;

d. cardioprotective effect - reduction of markers of myocardial damage

e. Reduction of anxiety, depression, cognitive impairment (Politov M.E., Podprugina S.V., Zolotova E.N., Nogtev P.V., Agakina Yu.S., Zhukova S.G., Yavorovsky A.G. Clinical use of xenon in subanesthetic concentrations (review). General Reanimatology. 2025;21(2):55-67. https://doi.org/10.15360/1813-9779-2025-2-2554)

The inhalation method of administering a pre-mixed gas mixture allows for a more pronounced effect, which manifests itself more quickly. Furthermore, this method of delivering the mixture is simple to use. The ease of administration of the gas mixture is an advantage for patients undergoing toxic chemotherapy treatments, which impact both psychological and physical health. It utilizes small doses of gases without compromising effectiveness, and the rapid response to the administered mixture is achieved due to the rapid penetration of the gas mixture into the most remote areas of the respiratory system.

Regarding the use of gases in medical practice, it is well known that the effect of a given drug depends both on the penetration of the administered drug or mixture into the bronchial tree (bronchi, bronchioles, alveoli) and on its chemical structure. Thus, the achieved effect is directly dependent on the dose of the gas mixture.

The studies conducted by the authors showed that in order to reduce neuro- and cardiotoxicity during chemotherapeutic treatment in patients with breast cancer, it is necessary to use experimentally selected mixtures consisting of xenon and oxygen, using a target 25-40 wt.% content of xenon as a factor with organoprotective properties that counteract the development of the toxic effect of the chemotherapeutic drug on the brain, heart, kidneys, liver, and hematopoietic organs.

Preclinical studies have shown that xenon inhalation at concentrations of 25-40% can achieve the aforementioned effects. However, lower concentrations do not provide the stated effect, while higher concentrations have a negative impact on organs and organ systems and can cause side effects and complications, such as nausea or vomiting.

Implementation of the invention.

To reduce organotoxicity (namely, neuro-, cardio-, hepato- and nephrotoxicity) in patients with breast cancer during chemotherapy, inhalations of a xenon-oxygen mixture are used, wt. %: Xe 25-40%, O₂ 60–75%.

Functional assessments included ECG, hemodynamics, and SpO₂. Laboratory and instrumental studies were performed at baseline (day 0) and on days 7 and 15.

This is due to the fact that:

on day 0, initial laboratory and instrumental parameters are assessed to enable tracking the dynamics of their changes during chemotherapy;

on the seventh day - according to the pharmacokinetics of chemotherapy drugs and literary data, days 7-10 correspond to the peak of manifestations of acute organ damage after chemotherapy, and surveys allow us to assess earlier manifestations of toxicity;

Day 15 - reflects delayed organ damage and recovery dynamics.

Cardiotoxicity indicators were assessed using troponin testing and echocardiography, as well as blood function tests (Hb, erythrocytes, leukocytes, neutrophils, and platelets). Quality of life was assessed using the EORTC QLQ-C30 and EQ-5D-5L questionnaires, psychoemotional state was assessed using the PHQ-9 and GAD-7 questionnaires, and the severity of nausea and vomiting was assessed using the MASSC questionnaire.

The invention is illustrated by the following example, which explains the essence of the invention.

Example.

Patient G., 53, was admitted to the clinical center of the I.M. Sechenov First Moscow State Medical University with a diagnosis of stage IIA (pT1cN2M0), luminal type A right breast cancer, following radical resection on December 19, 2024. High-intensity adjuvant chemotherapy was planned according to the TC regimen: docetaxel and cyclophosphamide, filgrastim to stimulate leukopoiesis.

The first course of chemotherapy was administered on January 29, 2025, followed by a second course 22 days later. The first course, administered at a different healthcare facility using a docetaxel + cyclophosphamide regimen with additional empegfilgrastim to prevent leukopenia, was complicated by an episode of transient ischemic attack and seizures. The patient was examined by a neurologist; neuroimaging revealed no structural brain damage, and the ECG showed no rhythm disturbances.

Diagnosis: right breast cancer, pT1cN2M0, stage IIA, luminal type A. Concomitant diagnosis: hypertension stage I, grade 2, cardiovascular risk 2, hypercholesterolemia IIa. The Karnofsky index on admission was 80% - self-care ability was preserved and there was a moderate decrease in activity. The ECOG assessment was 1 point, physical activity was limited without loss of ability to work. The Charlson comorbidity index was 3 - including a malignant neoplasm without metastases and a history of transient ischemic attack.

The patient was included in a pilot clinical study evaluating the efficacy and safety of inhaled subanesthetic doses of xenon for organ toxicity during chemotherapy.

As part of the study, the patient underwent xenon-oxygen mixture inhalation sessions: Xe 30 wt. %, O₂ 70 wt. % while undergoing chemotherapy. Concurrently, body functions were monitored through the following studies: ECG, hemodynamics and SpO₂ assessment. Laboratory and instrumental studies were performed at baseline on day 0, as well as on days 7 and 15. Cardiotoxicity indicators were assessed: troponin, echocardiography, blood functions (Hb, erythrocytes, leukocytes, neutrophils, platelets), quality of life (EORTC QLQ-C30, EQ-5D-5L questionnaires), psychoemotional state (PHQ-9 and GAD-7 questionnaires), and the severity of nausea and vomiting (MASSC questionnaire).

To objectively assess potential neuroinflammation, serial measurements of S100B levels—a marker of astroglial activation and impaired blood-brain barrier permeability—were also performed. The patient's baseline S100B levels were determined, and a dynamic study was also conducted during xenotherapy.

The patient's baseline parameters were as follows: she rated her condition as satisfactory, with a VAS score of 80 and no complaints. Laboratory tests at the time of hospitalization revealed a high troponin T level of 55.1 ng/L (normal range: 0-14 ng/L). An ECG revealed sinus rhythm, incomplete right bundle branch block, and no signs of myocardial ischemia. These changes were assessed as biochemical manifestations of cardiotoxicity that developed after the first course of chemotherapy.

Furthermore, the patient continued to have leukopenia and anemia after the first course of chemotherapy. No other significant laboratory or instrumental changes were detected.

All inhalation therapy sessions using subanesthetic doses of xenon with a target Xe concentration of 30% wt were well tolerated by the patient. Inhalations were performed in the anesthesiology and intensive care unit with mandatory monitoring of vital signs and parameters: consciousness, heart rate, blood pressure, SpO₂, and resting ECG.

During each session:

• The patient’s level of consciousness corresponded to the RASS scale=-1 – she maintained eye contact, but at the same time showed reduced spontaneous activity and was drowsy;

• The patient did not make any complaints;

• Blood pressure and heart rate remained within physiological norms - changes during the procedure did not exceed 10%;

• Hemoglobin oxygen saturation (SpO₂) was consistently maintained at 100%;

• No rhythm disturbances were recorded on the ECG, or signs of respiratory depression.

The patient reported a subjective feeling of relaxation and reduced anxiety after each session. No adverse reactions, such as dizziness, headache, weakness, or paresthesia, were observed. Hoarseness, dysgeusia, or other side effects potentially associated with xenon inhalation were also not reported.

The dynamics of these parameters were also studied at days 7 and 15 following chemotherapy and a course of inhalation of a xenon-oxygen mixture: Xe 30 wt.%, O₂ 70 wt.% (Table 1). A decrease in the troponin T level was observed from 55.1 ng/L to 49.8 and then to 31.7 ng/L, which may indicate the absence of signs of chemoinduced cardiotoxicity. According to echocardiography, no impairment of myocardial contractility was observed; LV ejection fraction increased from 66% to 74%, remaining within normal limits, without signs of systolic dysfunction or pulmonary hypertension. In addition to an increase in the ejection fraction, the patient also showed a decrease in the left ventricular end-diastolic and systolic volumes (LVEDV and LVESV); these changes were more pronounced on the 7th day of the study, that is, 2 days after three sessions of inhalation of a xenon-oxygen mixture: Xe 30 wt. %, O₂ 70 wt. %.

According to the patient's ECG data on day 7 of the study, minor signs of repolarization disturbance were observed: decreased T-wave amplitude in II, III, aVF, and V3–V5, which resolved by the 15th control day. No nausea, vomiting, or significant electrolyte disturbances were observed.

Blood counts by day 7 showed myelosuppression: decreased WBC, lymphocyte, and platelet counts, typical after chemotherapy. By day 15, their recovery was observed due to stimulation of leukopoiesis. Also noteworthy is the increase in hemoglobin concentration during xenotherapy (Table 2).

Quality of life and psychoemotional state were assessed using the validated PHQ-9, GAD-7, EORTC QLQ-C30, EQ-5D-5L questionnaires, as well as the visual analog scale (VAS). Results were analyzed dynamically on days 0, 7, and 15 of the study (Table 3).

During chemotherapy combined with subanesthetic xenon inhalations, the patient demonstrated positive dynamics across all scales. Her PHQ-9 score (assessment of depressive symptoms) decreased from 4 to 1, indicating a transition from mild depression to a normal mood. Similarly, her GAD-7 score (assessment of anxiety) decreased from 7 to 2, indicating a significant reduction in anxiety.

Improvement in overall well-being was also confirmed by the EQ-5D-5L scale: the score decreased from 14 to 7, indicating a reduction in the degree of limitations in daily life. Subjective perception of one's own well-being on the visual analog scale (VAS) increased from 80 to 100 points, indicating a significant improvement in overall well-being.

According to the EORTC QLQ-C30 scale, which reflects the overall quality of life of cancer patients, positive dynamics were also noted - a decrease from 59 to 51, which is interpreted as a decrease in the severity of symptoms.

It is important to emphasize that the patient did not experience any significant episodes of nausea or vomiting during the observation period, as confirmed by the MASSC questionnaire and the patient's subjective assessment. The absence of gastrointestinal side effects may further indicate the positive impact of xenon therapy on chemotherapy tolerability.

Thus, a comprehensive assessment of quality of life shows that the use of xenon during chemotherapy can contribute not only to a reduction in toxicity, but also to an improvement in the overall physical and psycho-emotional state of the patient.

A key aspect of the study was to evaluate the impact of xenon therapy on cardiotoxic myocardial injury that developed after the first course of chemotherapy. Prior to the second course of chemotherapy, patient G. had elevated troponin T levels of 55.1 ng/L (with a normal range of up to 14 ng/L), suggesting these changes were biochemical signs of chemotherapy-induced cardiotoxicity. An ECG revealed no signs of ischemia, and an echocardiogram revealed a left ventricular ejection fraction (LVEF) of 66%, which was within normal limits but did not rule out subclinical injury.

Information on the patient's cognitive function was obtained using the EORTC QLQ-C30 and PHQ-9 questionnaires. The patient did not complain of memory loss, concentration problems, or mental slowness, and her scores on the relevant scales remained low.

To objectively assess potential neuroinflammation, serial measurements of S100B levels—a marker of astroglial activation and impaired blood-brain barrier permeability—were also performed. The patient's baseline S100B level was 0.64 ng/ml, exceeding typical values for healthy individuals and reflecting the effects of previous chemotherapy and the seizure episode. Laboratory variability cannot be ruled out. However, S100B levels did not increase dynamically after xenon therapy, and by day 15 they had decreased to 0.48 ng/ml, which can be interpreted as the absence of progressive neuroinflammation or new neuronal damage.

Following xenon inhalation therapy sessions with a gas mixture ratio of 30% Xe and 70% O2, positive dynamics were observed during patient monitoring during the first five days of the second course: troponin levels decreased to 49.8 ng/L on day 7 and to 31.7 ng/L by day 15. Simultaneously, an increase in LVEF to 74% was observed, as well as a moderate decrease in LV end-diastolic and systolic volumes according to echocardiography, which may reflect improved myocardial contractility.

An additional aspect worthy of attention is the possible influence of xenon therapy on hematopoiesis processes in the case of patient G.; correction of anemia persisting after the first course of chemotherapy was noted; an increase in hemoglobin levels from 114 to 124 g/l by day 15 was noted, which may be associated with the stimulating effect of xenon on erythropoiesis.

Another important aspect of the study was the impact of xenon therapy on the patient's quality of life. A comprehensive assessment using the PHQ-9, GAD-7, EORTC QLQ-C30, EQ-5D-5L, and visual analog scale (VAS) questionnaires revealed significant improvements as early as day 7, which persisted through day 15 of observation. The depression score on the PHQ-9 decreased from 4 to 1, and the anxiety score on the GAD-7 decreased from 7 to 2 points, reflecting a transition from mild impairment to normal. The EQ-5D-5L score, which measures the degree of limitations in daily life, decreased from 14 to 7, and the patient rated her overall condition as improved from 80 to 100 points on the VAS scale. This was accompanied by an improvement on the EORTC QLQ-C30 scale from 59 to 51, indicating a reduction in symptom severity.

Thus, this example highlights the multi-target therapeutic potential of xenon, including its neuroprotective, cardioprotective, and psychoprotective effects, as well as its potential to improve the quality of life of patients undergoing aggressive cancer treatment. This underscores the feasibility of further large-scale studies and expanded use of xenon in clinical oncology.

We also conducted experimental studies involving 40 female patients over 18 years of age with breast cancer who were eligible for chemotherapy. The patients were randomly divided into two groups of 20 patients each: the intervention group and the control group, with a 1:1 ratio.

As an intervention in the present study, subjects of the intervention group (Xe group, n = 20 patients), in addition to the therapy received within the framework of the regulated standard of care at the study center, were given three inhalations of an oxygen-xenon mixture with a xenon concentration of 25%-40% for at least 30 minutes: on the day of chemotherapy before its administration, on the third day from the start of chemotherapy, and on the fifth day from the start of chemotherapy.

Subjects in the control group (Ox group, n = 20 patients), in addition to the therapy recommended within the framework of the regulated standard of medical care at the research center, will be given three inhalations of an oxygen-nitrogen mixture with an oxygen concentration of 50% for 30 minutes as a placebo: on the day of chemotherapy, on the third day from the start of chemotherapy, and on the fifth day from the start of chemotherapy.

The said experimental study was conducted with the aim of assessing:

- the severity of the development of cardiotoxic effects of chemotherapy based on changes in troponin, pro-NBNP and echocardiography data.

- the severity of the development of nephrotoxic effects of chemotherapy, assessed on the basis of changes in the parameters: creatinine, urea, potassium, SCF;

- the severity of the development of hepatotoxic effects of chemotherapy, assessed on the basis of changes in the parameters: ALT, AST, Bilirubin;

- the severity of the development of neurotoxic effects of chemotherapy, assessed on the basis of changes in parameters: S100b protein.

Regarding the dynamics of the troponin indicator, the following should be noted.

In Group 0, the overall change in troponin levels was statistically significant according to the Friedman test (p = 0.0012). Pairwise comparisons revealed a significant increase in concentration from Day 0 to Day 7 (paired t-test, p = 0.0015, padj = 0.0029). Changes between Day 7 and Day 15 were statistically insignificant (p = 0.209, padj = 0.417).

In group 1, the overall dynamics of troponin levels were not statistically significant (Friedman, p = 0.391). Pairwise comparisons between time points also did not reveal significant changes: Troponin_0 → Troponin_1 (Wilcoxon, p = 0.272, padj = 0.544), Troponin_1 → Troponin_2 (p = 0.983, padj = 1.000).

Table 4 clearly demonstrates the differences in troponin concentration between the groups on days 7 and 15; an increase in troponin in the control group indicates damage to the heart muscle, while in the xenon group, troponin increases slightly, indicating cardioprotection and cardioprotective action of xenon.

As for the ECHO-CG parameters, the study results revealed a significant effect on the ejection fraction: the adjusted difference between groups was +4.66% in favor of the intervention (95% CI: 2.41 – 6.91, p = 0.0002, p-FDR = 0.0008).

Thus, the study of ECHO-CG parameters revealed a statistically significant and potentially clinically significant improvement in ejection fraction in patients who received the intervention, which also indicates the cardioprotective and cardioprotective effect of xenon.

Regarding the dynamics of S100b protein concentration, the following results were obtained.

In group 0, the median S100b protein concentration increased from 0.950 (IQR = 0.770) at the initial time point to 1.450 (IQR = 0.890) at the final time point. In group 1, the concentration remained relatively stable: the median at the initial time point was 1.000 (IQR = 0.685), and at the second time point it was 0.955 (IQR = 0.913).

Thus, in group 0, a significant increase in S100b concentration was detected over time (between all time points), while in group 1 the indicator remained stable. Differences between the groups did not reach statistical significance, but at the final stage, a pronounced tendency toward divergence was revealed (p(raw)=0.0266, p(adj)=0.0798).

This demonstrates the neuroprotective effect of xenon.

The following data were obtained regarding the dynamics of the concentration of ALT, AST, Total bilirubin and the De Ritis Ratio (AST/ALT).

ALT levels showed an increasing trend in both groups. In the control group, ALT levels increased from 25.5 to 37.5 U/L by day 15, while in the xenon therapy group, they increased from 26.4 to 31.7 U/L. Although absolute values were moderate and did not exceed reference limits, the rate of increase was less pronounced in the xenon therapy group, which may indicate a potential hepatoprotective effect.

AST also increased in both groups, but its amplitude was smaller: from 28.4 to 29.2 U/L in the control group and from 23.1 to 27.2 U/L in the xenon therapy group. Thus, by day 15, the differences between the groups in AST had virtually disappeared, indicating comparable levels of enzymatic response from hepatocytes and extrahepatic tissues.

Total bilirubin decreased in both groups. Patients receiving xenon therapy experienced a more pronounced decrease (from 11.4 to 9.1 μmol/L), while in the control group, bilirubin levels decreased moderately (from 13.8 to 12.9 μmol/L).

The De Ritis ratio (AST/ALT) significantly decreased in both groups. In the control group, it fell from 1.22 to 0.87, while in the xenon therapy group, it fell from 1.01 to 0.93. A ratio decrease of <1 is characteristic of the predominance of the cytosolic enzyme ALT, indicating a cytolytic type of hepatocellular injury. The more gradual and less pronounced decrease in DR in the xenon therapy group can be interpreted as a relative reduction in cytolysis with xenon therapy.

The laboratory data indicated indicate the hepatoprotective effect of xenon.

Analysis of biochemical markers of renal function (urea, creatinine, estimated glomerular filtration rate - eGFR) revealed no significant differences between the groups at any time point (days 0, 7, and 15; p>0.05 before and after Bonferroni correction). However, the trajectories of changes in the control and study groups differed in direction.

Serum creatinine remained within reference ranges in both groups throughout the observation period. In the control group, an increase was observed from 76.5 to 79.9 μmol/L, while in the xenon therapy group, it increased from 74.5 to 76.8 μmol/L. These data may indicate more stable renal filtration capacity with additional inhalation therapy.

Urea levels showed contrasting trends: in the control group, a gradual decrease was observed (from 6.3 to 5.8 mmol/L), while in the xenon therapy group, an initial increase from 5.3 to 5.9 mmol/L was observed, followed by stabilization. Levels in both groups remained within normal limits, ruling out a pronounced azotemic effect of the chemotherapy drugs.

Estimated GFR (eGFR) decreased in both groups, but more significantly in the control group. In patients without xenon therapy, eGFR decreased from 76.4 to 73.7 ml/min/1.73 m², while in the study group, it decreased from 79.9 to 77.6 ml/min/1.73 m². This may be regarded as indirect evidence of the nephroprotective effect of xenon under chemotherapy.

The above clearly demonstrates that the use of a xenon-oxygen mixture reduces organotoxicity, possessing neuro-, cardio-, nephro-, hepato- and psychoprotective effects.

Thus, the conducted studies have shown that the specified effects are achieved with the use of various combinations of quantitative values of the xenon and oxygen mixture from the ranges of wt. %: Xe 25 - 40%, O₂ 60 - 75%. Neuro-, cardio-, nephro-, hepato- and psychoprotective effects, an increase in the quality of life of patients were achieved in all subjects and with a xenon value of 25% and oxygen 75%, and with a xenon value of 35% and oxygen 65%, with a xenon value of 40% and oxygen 60%. As for the duration of inhalation, we have found that to achieve a neuro-, cardio- and psychoprotective effect, a duration of 30 minutes is minimal, but sufficient. However, the effects are also achieved with inhalation for 35, 40, etc. minutes, the duration being determined by the individual characteristics of the patient associated with the tolerance of the inhalation procedure itself. The volume of one inhalation of xenon-oxygen mixture is 5-6 liters, which is standard for inhalation of inert gases.

Claims (1)

The use of an inhalation composition consisting of the following gases, wt. %: xenon 25-40 and oxygen 60-75, as a means of reducing organotoxicity in patients with breast cancer during chemotherapy.