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

Abstract

Chemotherapy, targeted therapy, and immunotherapy are used against advanced non-small cell lung cancer. A clinically efficacious method for relieving the adverse events associated of such therapies is lacking. Fifty-eight adult patients were enrolled in our trial to relieve pulmonary symptoms or the adverse events of drugs. Twenty patients who refused drug treatment were assigned equally and randomly to a hydrogen (H₂)-only group and a control group. According to the results of tumor-gene mutations and drug-sensitivity tests, 10, 18, and 10 patients were enrolled into chemotherapy, targeted therapy, and immunotherapy groups in which these therapies were combined with H₂-therapy, respectively. Patients underwent H₂ inhalation for 4-5 hours per day for 5 months or stopped when cancer recurrence. Before study initiation, the demographics (except for tumor-mutation genes) and pulmonary symptoms (except for moderate cough) of the five groups showed no significant difference. During the first 5 months of treatment, the prevalence of symptoms of the control group increased gradually, whereas that of the four treatment groups decreased gradually. After 16 months of follow-up, progression-free survival of the control group was lower than that of the H₂-only group, and significantly lower than that of H₂ + chemotherapy, H₂ + targeted therapy, and H₂ + immunotherapy groups. In the combined-therapy groups, most drug-associated adverse events decreased gradually or even disappeared. H₂ inhalation was first discovered in the clinic that can be used to control tumor progression and alleviate the adverse events of medications for patients with advanced non-small cell lung cancer. This study was approved by the Ethics Committee of Fuda Cancer Hospital of Jinan University on December 7, 2018 (approval No. Fuda20181207), and was registered at ClinicalTrials.gov (Identifier: NCT03818347) on January 28, 2019.

Keywords: NSCLC; PFS; adverse event; chemotherapy; hydrogen; immunotherapy; non-small-cell lung cancer; progression-free survival; targeted drug.

Figure 1

Symptom comparison of patients in each group before and after hydrogen treatment. Note: Chemo: Chemotherapy; H₂: hydrogen; Immuno: immunotherapy; NSCLC: non-small-cell lung cancer; Target: targeted therapy.

Figure 2

Tumor-associated symptoms varied with the inhalation time of hydrogen (H₂). Note: (A) Control group (inhalation of 33.3% oxygen gas and no H₂ (n = 10). (B) H₂ only group (inhalation of 66.7% H₂ + 33.3% O₂) (n = 10). Each tumor-associated symptom was compared using linear regression analysis.

Figure 3

Drug-associated symptoms varied with the inhalation time of hydrogen (H₂). Note: (A) Immunotherapy-H₂ group (n = 10). (B) Target-H₂ therapy group (n = 18). (C) Chemotherapy-H₂ therapy group (n = 10). Drug-associated adverse event was compared using linear regression analysis.

Figure 4

Comparison of progression-free survival (PFS) between groups after hydrogen (H₂) treatment. Note: PFS of each group was compared by one-way analysis of variance and Bonferroni's multiple comparison test. *P < 0.05, **P < 0.01, ***P < 0.001.