Hydrogen therapy can be used to control tumor progression and alleviate the adverse events of medications in patients with advanced non-small cell lung cancer

Discussion

Molecular H2 has been used to treat pulmonary symptoms in animal models of acute lung injury,18,19,20,21 asthma22 and chronic obstructive pulmonary disease.23,24,25 The principle of H2 therapy includes inhibition of secretion of cytokines such as interleukin-4, interleukin-13,22 interleukin-6 and tumor necrosis factor-α.15 H2 therapy can alleviate pulmonary inflammation without impairing anti-tumor effects.14,26 Therefore, H2 gas can be adopted as adjuvant therapy to suppress these symptoms.

Chemotherapy, targeted therapy, and immunotherapy are first-line treatments against advanced NSCLC.27,28,29 The vastly increased generation of reactive oxygen species during treatment is believed to contribute to adverse events, resulting in oxidative stress, inflammation and apoptosis.30,31 In the present study, H2 therapy was shown to alleviate drug-related adverse events, most of which have been reported in animal models, including lung injury caused by various factors,18,19,20,21 hepatobiliary diseases,32,33,34 maculopapular rash,35 diarrhea and constipation,36,37,38 nausea and vomiting,39,40 oral mucositis,41,42 anemia,43 thrombocytopenia,44 and anorexia.45 We found that the prevalence of insomnia, dizziness and headache could be reduced significantly after H2 inhalation, which could be related to relief of diseases of the central nervous system, such as cerebral hemorrhage,46,47,48 Parkinson's disease49,50 and Alzheimer's disease,51,52 observed in animal experiments. The mechanism of action observed in animal experiments could be used as a reference for clinical research. Surprisingly, H2 therapy, which is non-toxic and can alleviate adverse events in multiple organs simultaneously, has been used rarely.

We found that H2 monotherapy could prolong the PFS of patients with advanced NSCLC from 4.4 ± 1.2 months to 7.9 ± 2.2 months, suggesting that H2 could inhibit the growth of lung cancer cells independently. This hypothesis has been bolstered by data from an in vitro and in vivo study, which confirmed that H2 can inhibit the proliferation, migration, and invasion of the lung-cancer cell lines and tumor growth in mouse model.53 These data suggested that H2 could serve as new therapy against lung cancer. However, for patients eligible for first-line treatment, drugs will produce more pronounced effects upon tumor control. Whether a combination of drug therapy and H2 therapy can elicit better tumor control must be studied further, but gradual reduction of most drug-associated adverse events after H2 inhalation is clear.

Several delivery methods of molecular H2 are available and convenient: inhalation, drinking H2-dissolved water, injection with H2-saturated saline, and taking a “H2 bath.”54 H2 is non-toxic, inexpensive, can be administered readily, can diffuse into tissues and cells55 and cross the blood–brain barrier.56 Hence, H2 could be used to treat tumors of the head, neck and chest. Because of the risk of explosion of H2 and oxygen mixed in air, often such gas mixtures are inhaled using catheters and masks whereas, in animal experiments, drinking or injection of H2-dissolved water is employed. Use of a machine with a sufficiently high flow rate (3 L/min) and inhalation duration every day (4–6 hours) of H2 in this trial may enable control of tumor growth and reduce the prevalence of adverse events of drugs.

In general, H2 inhalation was first discovered in the clinic that can be used to control tumor progression and alleviate the adverse events of medications in patients with advanced NSCLC. The main limitation of this study is that the number of patients enrolled is relatively small, and more accurate patient benefits are still awaiting the results of large samples. Whether this therapeutic effect can be improved further, as well as determination of the synergistic effect of drugs and H2 therapy, must be explored further.

Footnotes

References