Hidrogenul ameliorează efectele secundare ale medicamentelor împotriva cancerului pulmonarCercetare Științifică

titlu original: Terapia cu hidrogen poate fi utilizată pentru a controla progresia tumorii și pentru a atenua efectele adverse ale medicamentelor la pacienții cu cancer pulmonar avansat cu celule non-mici.

Publicat pe: 05/06/2020

Rezumat

Chimioterapia, terapia țintită și imunoterapia sunt utilizate pentru a trata cancerul pulmonar avansat cu celule non-mici. Există o lipsă de metode eficiente din punct de vedere clinic pentru a îmbunătăți evenimentele adverse asociate cu astfel de terapii. Cincizeci și opt de pacienți adulți au participat la studiul nostru pentru ameliorarea simptomelor pulmonare sau a efectelor secundare ale medicamentelor. Douăzeci de pacienți care au refuzat tratamentul medical au fost repartizați în mod egal și repartizați în mod aleatoriu în grupuri de doar hidrogen (H2) și de control. Pe baza mutațiilor genetice tumorale și a rezultatelor testelor de sensibilitate la medicamente, 10, 18 și 10 pacienți au fost incluși în grupul de chimioterapie, în grupul de terapie țintită și, respectiv, în grupul de imunoterapie, unde aceste tratamente au fost combinate cu terapia H2.

Pacienții inhalează H2 4-5 ore pe zi, timp de 5 luni, sau se opresc atunci când cancerul recidivează. Înainte de începerea studiului, nu au existat diferențe semnificative în ceea ce privește datele demografice (cu excepția genelor mutante din tumori) și simptomele pulmonare (cu excepția tusei moderate) între cele cinci grupuri. În timpul primelor 5 luni de tratament, incidența simptomelor în grupul de control a crescut treptat, în timp ce incidența simptomelor în cele patru grupuri de tratament a scăzut treptat. După 16 luni de urmărire, supraviețuirea fără progresie în grupul de control a fost mai mică decât cea din grupul H2 singur și a fost semnificativ mai mică decât cea din grupul H2+ chimioterapie, H2+ terapie țintită și H2+ imunoterapie.

În grupul de tratament combinat, majoritatea evenimentelor adverse legate de medicamente au scăzut treptat sau chiar au dispărut. Metoda de inhalare H2 a fost descoperită pentru prima dată în clinică și poate fi utilizată pentru a controla progresia tumorii și pentru a reduce efectele secundare ale medicamentelor la pacienții cu cancer pulmonar avansat cu celule non-mici. Acest studiu a fost aprobat de Comitetul de Etică al Spitalului de Cancer Fuda al Universității Jinan la 7 decembrie 2018 (nr. de aprobare Fuda20181207) și a fost înregistrat la ClinicalTrials.gov la 28 ianuarie 2019 (nr. NCT03818347).

Concluzia cercetării

Am constatat că monoterapia cuH₂ ar putea prelungi PFS a pacienților cu NSCLC avansat de la 4,4 ± 1,2 luni la 7,9 ± 2,2 luni, sugerând căH₂ ar putea inhiba în mod independent creșterea celulelor canceroase pulmonare. Această ipoteză a fost susținută de datele unui studiu in vitro și in vivo, care a confirmat căH₂ poate inhiba proliferarea, migrarea și invazia liniilor celulare de cancer pulmonar și creșterea tumorii în modelul de șoarece.^[53]

Aceste date au sugerat căH₂ ar putea servi ca o nouă terapie împotriva cancerului pulmonar. Cu toate acestea, pentru pacienții eligibili pentru tratamentul de primă linie, medicamentele vor produce efecte mai pronunțate asupra controlului tumorii. Trebuie studiat în continuare dacă o combinație de terapie medicamentoasă și terapie cu H₂ poate determina un control mai bun al tumorii, dar reducerea treptată a majorității evenimentelor adverse asociate cu medicamentele după inhalarea deH₂ este clară.

Publicație Originală

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

DOI:  10.4103/2045-9912.285560

Ji-Bing Chen¹, Xiao-Feng Kong², Feng Mu², Tian-Yu Lu¹, You-Yong Lu³, Ke-Cheng Xu¹

Abstracts

Chemotherapy, targeted therapy, and immunotherapy are used to treat advanced non-small cell lung cancer. There is a lack of clinically effective methods to improve adverse events associated with such therapies. Fifty-eight adult patients participated in our study for relief of pulmonary symptoms or drug side effects. Twenty patients who refused medical treatment were equally allocated and randomly assigned to hydrogen-only (H2) and control groups. Based on tumor gene mutations and drug susceptibility test results, 10, 18, and 10 patients were included in the chemotherapy group, the targeted therapy group, and the immunotherapy group, respectively, where these treatments were combined with H2 therapy, respectively. Patients inhale H2 4-5 hours a day for 5 months, or stop when cancer recurs. Before the start of the study, there were no significant differences in demographics (except for mutated genes in tumors) and pulmonary symptoms (except for moderate cough) among the five groups. During the first 5 months of treatment, the incidence of symptoms in the control group gradually increased, while the incidence of symptoms in the four treatment groups gradually decreased. After 16 months of follow-up, the progression-free survival in the control group was lower than that in the H2 group alone, and was significantly lower than that in the H2+ chemotherapy group, the H2+ targeted therapy group, and the H2+ immunotherapy group. In the combination treatment group, most drug-related adverse events gradually decreased or even disappeared. The H2 inhalation method was first discovered clinically and can be used to control tumor progression and reduce drug side effects in 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 with ClinicalTrials.gov on January 28, 2019 (No. NCT03818347).

Results

Clinical data from patients with advanced non-small cell lung cancer receiving H2 inhalation therapy

Patients inhaled H2 daily for 5 months or stopped when the cancer recurred. Most patient characteristics, such as gender, were not significantly different within each group. However, the targeted therapy and H2 therapy groups had a higher proportion of tumor gene mutations than the other four groups (p=0.005; [Table 1].

Table 1: Patient demographics of advanced non-small cell lung cancer patients in different groups

Pulmonary signs and symptoms of advanced non-small cell lung cancer patients with H₂ inhalation treatment

There were no significant differences in lung function or KPS scores between the five groups of patients before starting H2 therapy [Table 2]. The incidence of most pulmonary symptoms (eg, mild dyspnea, noncardiac chest pain, pleural effusion, and hemoptysis) was similar between groups. The incidence of most pulmonary symptoms was higher in the control group, H2 monotherapy group, and immunotherapy H2 treatment group than in the targeted therapy H2 treatment group and chemotherapy H2 treatment group (p=0.0137).

 

Table 2: Pulmonary signs and symptoms before hydrogen therapy of advanced non-small cell lung cancer patients with H₂ inhalation treatment

Tumor-associated symptoms of advanced non-small cell lung cancer patients with H₂ inhalation treatment

The incidence of tumor-related symptoms was similar in the control and H2 monotherapy groups at the start of H2 therapy (p=0.9994). With increasing treatment time, the control group developed moderate cough (P = 0.0023), mild dyspnea (P = 0.0019), mild non-cardiac chest pain (P = 0.0006), mild pleural effusion (P = 0.0006) 0.0023) and mild hemoptysis (P=0.0028) significantly increased [Figure 2]A. Moderate cough (P=0.0014), mild dyspnea (P=0.0247), mild non-cardiac chest pain (P=0.0136), mild pleural effusion (P=0, 0015) and H2 monotherapy group The incidence of mild hemoptysis (P=0.0048) decreased significantly [Fig. 2]B.

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.

Drug-associated adverse events of advanced non-small cell lung cancer patients with H₂ inhalation treatment

The incidence of tumor-related symptoms was similar among the three groups at the start of H2 treatment (p=0.5120), but drug-related symptoms varied widely among the three groups [Figure 3]. The prevalence of cough and non-cardiac chest pain (p=0.0013), maculopapular rash (p=0.0021), hepatobiliary disease (p=0.0064), and dizziness and headache (p=0.0111) increased with treatment duration Decreased but not diarrhea (P=0.4144) [Figure 3]A. In the targeted therapy H2 treatment group, the incidence was febrile neutropenia (p=0.0026), nausea and vomiting (p=0.0051), maculopapular rash (p<0.0001), insomnia (p=0.0144) and oral mucositis (p=0.0001) ). 0.0007) significantly decreased [Figure 3]B.The incidence of febrile neutropenia (P=0.0086), anemia and thrombocytopenia (P=0.0009), constipation and diarrhea (P=0.0053), and anorexia (P=0.0129), but not nausea and vomiting, was significantly lower in the H2 chemotherapy group (P = 0.0720; [Figure 3] C

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.

PFS of advanced non-small cell lung cancer patients with H₂ inhalation treatment

After 16 months of follow-up, all 58 patients had tumor progression. PFS was 4.4 ± 1.2 months in the control group, 7.9 ± 2.2 months in the H2-only group, 10.1 ± 2.6 months in the H2 immunotherapy group, 9.4 ± 3.1 months in the H2-directed therapy group, and 8.5 ± 3.0 in the H2 chemotherapy group months. PFS was longer in all four treatment groups than in the control group, and PFS was significantly prolonged in the three H2 treatment combination groups [Figure 4].

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.

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