PURPOSE: The role of immunotherapy in the treatment of patients with advanced renal cell carcinoma(RCC) is being evaluated by a number of investigators. In this study, we evaluated the efficacy and toxicity of a low-dose subcutaneous regimen of interferon-alpha(IFN-alpha) in combination with intravenous administration of 5-fluorouracil(5-FU) with or without interleukin-2 (IL-2) in patients with advanced RCC. MATERIALS AND METHODS: 16 patients with advanced RCC were treated with an 8-week cycle of 6 to 9 MU/M2 IFN-alpha given 1 to 3 times a week during the 8 week period, and sequentially combined with 5 to 20 MU/M2 IL-2 given 3 times a week for 4 weeks and 750mg/M2 5-FU once a week for 4 weeks. 5 patients were treated with only IFN-alpha and 5-FU. Treatment schedule was identical except for the exclusion of IL-2 in this group. Among those 16 patients treated with 3-drug regimen(including IL-2), 10 patients had measurable metastatic lesions, and 4 patients had measurable metastatic lesions among 5 patients treated with 2-drug regimen(without IL-2). RESULTS: Among 19 consecutive men and 2 women treated, 14 had measurable metastatic lesion. 10 out of 14 patients with measurable metastatic lesions were treated with 3- drug regimen, and objective tumor regressions were achieved in 4 patients(40%) consisting of complete response in 1(10%) and partial response in the other 3(30%). Metastatic sites were lung in 3 patients, bone in 1 patient. 3 of the 4(75%) patients with pulmonary metastasis showed complete or partial response. Median response duration(complete plus partial response) was 14.3 months(range 11 to 22+). Stable disease lasting 3 months was noted in 1 patients(10%). Other 4 patients out of 14 patients with measurable metastatic lesions were treated with 2-drug regimen, and partial remission lasting 9 months was noted in 1 patient(25%). There were only mild to moderate side effects; maximum toxicity grade of 0 in 10 patients, grade I in 3, II in 7, III in 1 according to the World Health Organization classification. None of the patients experienced major IL-2 related toxicity and no toxic deaths occurred. CONCLUSIONS: This combination immunochemotherapy may be a promising regimen with modest toxicity in advanced RCC. The most favorable response can be expected in pulmonary metastasis. Most of side effects were tolerable. Three-drug regimen including IL-2 showed better response rate than two-drug regimen, suggesting a major role of IL-2. A large prospective randomized trials are required to confirm whether the combination immunochemotherapy has an effect on advanced RCC or not.
Administration, Intravenous ; Appointments and Schedules ; Carcinoma, Renal Cell* ; Classification ; Female ; Fluorouracil* ; Humans ; Immunotherapy ; Interferon-alpha* ; Interleukin-2* ; Lung ; Male ; Neoplasm Metastasis ; Research Personnel ; World Health Organization

BACKGROUND: Currently, there are no drugs that have been proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because of its broad antiviral activity, interferon (IFN) should be evaluated as a potential therapeutic agent for treatment of coronavirus disease 2019 (COVID-19), especially while COVID-19-specific therapies are still under development. METHODS: Confirmed COVID-19 patients hospitalized in the First Affiliated Hospital, School of Medicine, Zhejiang University in Hangzhou, China, from January 19 to February 19, 2020 were enrolled in a retrospective study. The patients were separated into an IFN group and a control group according to whether they received initial IFN-α2b inhalation treatment after admission. Propensity-score matching was used to balance the confounding factors. RESULTS: A total of 104 confirmed COVID-19 patients, 68 in the IFN group and 36 in the control group, were enrolled. Less hypertension (27.9% vs. 55.6%, P=0.006), dyspnea (8.8% vs. 25.0%, P=0.025), or diarrhea (4.4% vs. 19.4%, P=0.030) was observed in the IFN group. Lower levels of albumin and C-reactive protein and higher level of sodium were observed in the IFN group. Glucocorticoid dosage was lower in the IFN group (median, 40 vs. 80 mg/d, P=0.025). Compared to the control group, fewer patients in the IFN group were ventilated (13.2% vs. 33.3%, P=0.015) and admitted to intensive care unit (ICU) (16.2% vs. 44.4%, P=0.002). There were also fewer critical patients in the IFN group (7.4% vs. 25.0%, P=0.017) upon admission. Although complications during admission process were comparable between groups, the discharge rate (85.3% vs. 66.7%, P=0.027) was higher and the hospitalization time (16 vs. 21 d, P=0.015) was shorter in the IFN group. When other confounding factors were not considered, virus shedding time (10 vs. 13 d, P=0.014) was also shorter in the IFN group. However, when the influence of other factors was eliminated using propensity score matching, virus shedding time was not significantly shorter than that of the control group (12 vs. 15 d, P=0.206). CONCLUSIONS IFN-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients.
Albumins/analysis* ; Antiviral Agents/administration & dosage* ; Betacoronavirus ; C-Reactive Protein/analysis* ; COVID-19 ; Case-Control Studies ; China ; Coronavirus Infections/drug therapy* ; Glucocorticoids/pharmacology* ; Hospitalization ; Humans ; Interferon alpha-2/administration & dosage* ; Nasal Sprays ; Pandemics ; Pneumonia, Viral/drug therapy* ; Propensity Score ; Retrospective Studies ; SARS-CoV-2 ; Sodium/blood* ; Virus Shedding/drug effects* ; COVID-19 Drug Treatment

OBJECTIVETo observe the effect of Shenfu injection (SFI) and influence on T-lymphocyte subset, serum level of interferon-gamma(IFN-gamma), tumor necrosis factor-alpha(TNF-alpha), interleukin-2(IL-2) in patients with chronic aplastic anemia (CAA) based on treating with stanozol and cyclosporin A.

METHOD60 patients with CAA were randomly divided into two groups, 30 patients in the SFI group were treated with SFI (100 mL which contains Ginsenoside 0.8 mg x mL(-1) and aconitine 1.8 microg x mL(-1) by adding it in 500 mL of 5% glucose every day) plus stanozol and cyclosporin A and 30 patients in the control group treated with slanozol and cyclosporin A alone for 2 months. The clinical efficacy was observed. The change of T-lymphocyte subset analyzed by flow cytometry and the levels of serum IFN-gamma, TNF-alpha, IL-2 measured with ELISA method were also observed before and after treatment.

RESULTAfter treatment, the total effective rate of the SFI group was higher than that in the control group, but it did not showing significant difference. The CD4/CD8 levels were significantly increased (1.76+/-0.49, P< 0.01) and CD8 levels were significantly lowered (22.57+/-6.30, P < 0.01) in the SFI group after treatment. Serum levels of lFN-gamma, TNF-alpha and IL-2 were lower in both groups, and the level of TNF-alpha and IL-2 in the SFI group (0.710+/-0.213) ng x L(-1) and (0.639+/-0.247) ng x L(-1) was significantly lowered than that in the control group (P < 0.05, P < 0.01).

CONCLUSIONSFI might believe the hemopoietic inhibition so as to promote the recovery of hemopoietic function through improving the T-lymphocyte subset and reducing the release of hemopoietic negative regulatory factors such as IFN-gamma, TNF-alpha and IL-2.

Aconitine ; administration & dosage ; Adolescent ; Adult ; Aged ; Anemia, Aplastic ; blood ; drug therapy ; immunology ; CD4-CD8 Ratio ; Cyclosporine ; therapeutic use ; Drug Combinations ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Female ; Ginsenosides ; administration & dosage ; Humans ; Interferon-gamma ; blood ; Interleukin-2 ; blood ; Kidney Diseases ; blood ; drug therapy ; immunology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Phytotherapy ; Stanozolol ; therapeutic use ; Tumor Necrosis Factor-alpha ; metabolism ; Yang Deficiency ; blood ; drug therapy ; immunology