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BACKGROUND: Postoperative non-small cell lung cancer (NSCLC) patients frequently encounter a deteriorated quality of life (QOL), disturbed immune response, and disordered homeostasis. Si-Jun-Zi Decoction (SJZD), a well-known traditional Chinese herbal formula, is frequently employed in clinical application for many years. Exploration is underway to investigate the potential therapeutic effect of SJZD for treating postoperative NSCLC. OBJECTIVE: To assess the efficacy of SJZD on QOLs, hematological parameters, and regulations of gut microbiota in postoperative NSCLC patients. METHODS: A prospective observational cohort study was conducted, enrolling 65 postoperative NSCLC patients between May 10, 2020 and March 15, 2021 in Yueyang Hospital, with 33 patients in SJZD group and 32 patients in control (CON) group. The SJZD group comprised of patients who received standard treatments and the SJZD decoction, while the CON group consisted of those only underwent standard treatments. The treatment period was 4 weeks. The primary outcome was QOL. The secondary outcomes involved serum immune cell and inflammation factor levels, safety, and alterations in gut microbiota. RESULTS: SJZD group showed significant enhancements in cognitive functioning (P = .048) at week 1 and physical functioning (P = .019) at week 4. Lung cancer-specific symptoms included dyspnea (P = .001), coughing (P = .008), hemoptysis (P = .034), peripheral neuropathy (P = .019), and pain (arm or shoulder, P = .020, other parts, P = .019) eased significantly in the fourth week. Anemia indicators such as red blood cell count (P = .003 at week 1, P = .029 at week 4) and hemoglobin (P = .016 at week 1, P = .048 at week 4) were significantly elevated by SJZD. SJZD upregulated blood cell cluster differentiation (CD)3+ (P = .001 at week 1, P < .001 at week 4), CD3+CD4+ (P = .012 at week 1), CD3+CD8+ (P = .027 at week 1), CD19+ (P = .003 at week 4), increased anti-inflammatory interleukin (IL)-10 (P = .004 at week 1, P = .003 at week 4), and decreased pro-inflammatory IL-8 (P = .004 at week 1, p = .005 at week 4). Analysis of gut microbiota indicated that SJZD had a significant impact on increasing microbial abundance and diversity, enriching probiotic microbes, and regulating microbial biological functions. CONCLUSIONS: SJZD appears to be an effective and safe treatment for postoperative NSCLC patients. As a preliminary observational study, this study provides a foundation for further research.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Drugs, Chinese Herbal , Gastrointestinal Microbiome , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/drug therapy , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Quality of Life , Prospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Gastric cancer is a common cause of global mortality, with significant challenges during treatment due to side effects and complications. Traditional herbal medicine (THM) has emerged as a potential adjuvant therapy to enhance cancer treatment by reducing side effects and bolstering the immune response. This study conducted a meta-analysis to assess the efficacy and safety of THM as an adjuvant therapy in post-surgical gastric cancer patients. METHODS: PubMed, Cochrane Library, EMBASE, CNKI, CiNii, KMBASE, KISS, OASIS, RISS, and ScienceON databases were searched from inception through December, 2021. The outcomes considered in this analysis encompassed tumor response, quality of life (QoL), side effects, and tumor markers. Additionally, a frequency analysis of the most commonly used herbs in the included studies was conducted. A total of 36 randomized controlled trials (RCTs) were included, and data were extracted according to study design. The analysis compared groups receiving chemotherapy alone with those receiving both chemotherapy and THM treatment. RESULTS: The group receiving both chemotherapy and THM showed substantial improvement in tumor response compared to the chemotherapy-only control group (RR 1.25, 95% CI [1.09, 1.45]). QoL also significantly increased in the THM-treated group. Most drug adverse reactions displayed statistical significance, except for platelet reduction. Tumor markers CEA, CA19-9, and CA72-4 exhibited significant improvements, but CA125 did not. The 1, 2, and 3-year survival rates improved, with RR values of 1.08 (95% CI [1.02, 1.14]), 1.32 (95% CI [1.19, 1.47]), and 1.42 (95% CI [1.12, 1.79]) respectively. However, some publication bias was indicated. CONCLUSION: THM may offer potential benefits as a complementary approach to post-surgical anticancer therapy in gastric cancer patients. Improved tumor response, quality of life, and survival rates were reported. However, it is important to exercise caution due to the possibility of publication bias, and further research is needed to confirm these findings.Registration:PROSPERO CRD 42022354133.
Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/drug therapy , Herbal Medicine , Chemotherapy, Adjuvant , Biomarkers, Tumor , Plant Extracts , Randomized Controlled Trials as TopicABSTRACT
Malignant pleural mesothelioma (MPM) is a severe form of cancer that originates from mesothelium cells. Around 54-90% of mesotheliomas are associated with pleural effusions. Brucea Javanica Oil Emulsion (BJOE) is the processed oil derived from the seeds of Brucea javanica, which has shown potential as a treatment option for several types of cancer. Here, we present a case study of a MPM patient with malignant pleural effusion who received intrapleural injection of BJOE. The treatment resulted in the complete response of pleural effusion and chest tightness. While the precise mechanisms underlying the therapeutic effects of BJOE for pleural effusion are not yet fully understood, it has demonstrated a satisfactory clinical response without significant adverse effects.
Subject(s)
Brucea , Mesothelioma, Malignant , Mesothelioma , Pleural Effusion, Malignant , Humans , Brucea javanica , Emulsions/therapeutic use , Mesothelioma/complications , Mesothelioma/drug therapy , Plant Oils/therapeutic use , Pleural Effusion, Malignant/drug therapy , Pleural Effusion, Malignant/pathologyABSTRACT
BACKGROUND: Tongue diagnosis is a crucial traditional Chinese medicine (TCM) inspection method for TCM syndrome differentiation and treatment. OBJECTIVE: The primary research focus was on tongue image characteristic parameters of patients with non-small cell lung cancer (NSCLC). Analysis of the tongue image parameters of various pathological stages of NSCLC provides technical support for establishing an integrated Chinese and Western auxiliary diagnosis and efficacy evaluation medicine system for lung cancer that integrates tongue image features. METHODS: Tongue image characteristics of 309 patients with NSCLC and 206 controls were collected and analyzed clinically. The T-test or rank sum test and logistic regression analysis were applied to analyze the characteristics of tongue image indicators of different pathological stages of NSCLC. RESULTS: There were differences in tongue image characteristics in the NSCLC group compared to the control group. The tongue quality and brightness of the tongue coating in the NSCLC group increased, the red component was reduced, the tongue coating thickened, and the yellow component increased compared to the healthy control group. A comparison of tongue image indexes of NSCLC in different pathological stages showed that stage IV had lower TB-b and higher TB-a than stage I. In addition, stage IV had lower TB-b than stage II + III, showing an increase in the blue and red components of the tongue in stage IV and the appearance of cyanotic tongue features. CONCLUSION: The tongue image characteristics of NSCLC patients differed from those of the control group. Tongue imaging indicators can reflect the characteristics of tongue images of patients with NSCLC. The tongue image characteristics of patients with stage IV lung cancer are bluish and purple compared with those with stage I, II, and III. It is suggested that the tongue's image characteristics can be used as a reference for the pathological classification of NSCLC and judgment of the disease process.
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BACKGROUND: Bone metastasis is frequently common in advanced lung cancer with the major issue of a pathological fracture. Previous studies suggested that Astragalus membranaceus (Qi) and Ampelopsis japonica (Lian), which are used as folk medicine in China, have potential effects on inhibiting tumor growth and protecting bones, respectively. In this study, an experiment on the inhibitory effect of the Qilian formula (AAF) in vivo was designed to examine tumor growth in bone and osteoclast formation. MATERIALS AND METHODS: The bone metastasis xenograft models were established by implanting NCI-H460-luc2 lung cancer cells into the right tibiae bones of mice. After confirming the model's viability through optical imaging 7 days post-implantation, 2 groups, namely the AAF group and the control group, were administered 0.3 mL of AAF extract (9 g/kg/day) or normal saline via intragastric delivery for a duration of 4 weeks. Throughout the study, we longitudinally assessed tumor burden, bone destruction, and weight-bearing capacity in vivo using reporter gene bioluminescence imaging (BLI), micro-CT, and dynamic weight-bearing (DWB) tests. Mechanistic insights were gained through Hematoxylin-eosin (H&E) staining, immunohistochemical (IHC) analysis, western blotting, and flow cytometry. RESULTS: Qilian formula produced significant inhibition to the progress of bone destruction and tumor burden in the right tibiae bone in the treatment group. It was further evidenced by molecular imaging in vivo via small animal micro-CT and BLI with parametric quantification, characterizing significantly lower uptake of BLI signal in the treated tumor lesions and improving the pathological changes in the microstructure of bone. Furthermore, DWB tests revealed that Qilian formula treatment significantly maintained the weight-bearing capacity. According to immunohistochemical analysis, the effect of the Qilian formula appeared to involve the suppression of osteoclast formation by lower expression of the tartrate-resistant acid phosphatase. Cell apoptosis and death induction were evidenced by a higher percentage of Bal2ãBAX and caspase 3 expressions of Qilian formula-treated tumor tissues. CONCLUSIONS: Our study demonstrated a significant inhibitory effect of the Qilian formula on the progression of osteolytic invasion in vivo by suppressing osteoclastogenesis and promoting apoptotic cell death.
Subject(s)
Bone Neoplasms , Lung Neoplasms , Humans , Animals , Mice , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Bone Neoplasms/drug therapy , Cell Proliferation , Osteoclasts/metabolism , Osteoclasts/pathology , Cell Cycle , Cell Line, TumorABSTRACT
BACKGROUND: Cancer pain, a common complication of this disease, has been widely treated by electroacupuncture in recent years. However, there are numerous treatment parameters that are not conducive to clinical translation applications. This study aims to summarize the stimulation parameters commonly used in electroacupuncture treating cancer pain by data mining and visualization techniques to provide a basis for the future acupuncture technology transformation and selection of optimal stimulation parameters. METHODS: Nine databases, including Pubmed, Cochrane Library, Embase, Web of Science, OVID, China National Knowledge Infrastructure Database, China Biology Medicine disk, China Science and Technology Journal Database, and Wanfang Database, were searched for clinical studies on electroacupuncture treatment cancer pain published between January 2012 and September 2022. A database was established using Microsoft Excel 2020 and analyzed with SPSS Modeler 18.1 software and SPSS statistics 26.0 software. RESULTS: Twenty-four articles were included according to the established criteria. The most used electroacupuncture stimulation parameters were a dilatational wave, the current frequency of 2/100 Hz, stimulation duration of 30 minutes per treatment, and frequency of treatment once a day. Fifty-eight acupoints were mentioned, and the total frequency of acupoints involved was 156 times. The most used ones include Zusanli (ST36), Sanyinjiao (SP06), Hegu (LI04), Neiguan (PC06), Quchi (LI11), Taichong (LR03), Ashi point, Jiaji point, and those most generally used acupoints that are closely arranged on the Stomach Channel of Foot Yangming and the Spleen Channel of Foot Taiyin. The association analysis of acupoints revealed that the most supported acupoint pair was Sanyinjiao (SP06) and Zusanli (ST36). Cluster analysis demonstrated 3 groups, 1 for obligatory acupoints, 1 for Ashi point, and the third for Jiaji point. CONCLUSIONS: A dilatational wave, the current frequency of 2/100 Hz, 30-minute stimulation, and acupoints of the Stomach Channel of Foot Yangming and the Spleen Channel of Foot Taiyin selection are frequently used in electroacupuncture for treating cancer pain. Due to the limitations of this study, further research and more standardized, multi-center, large-sample clinical trials can be carried out to guide optimizing acupuncture treatment schemes and promote the formation of TCM-characteristic technologies for cancer pain.
Subject(s)
Acupuncture Therapy , Cancer Pain , Electroacupuncture , Meridians , Neoplasms , Humans , Cancer Pain/therapy , Data Mining , Neoplasms/complications , Neoplasms/therapyABSTRACT
INTRODUCTION: Although music therapy (MT) has been found to reduce anxiety in patients with cancer and delay tumour progression to some extent, its mechanism of action has not been determined. MT may reduce anxiety by reducing the concentrations of proinflammatory cytokines. The present study was designed to evaluate the effects of MT on anxiety and cytokine levels in patients with cancer. METHODS AND ANALYSIS: This randomised, open, single-centre parallel-controlled trial will randomise 60 patients with malignant tumours who meet the inclusion criteria in a 1:1 ratio to either an MT group or a non-MT (NMT) group. Patients in the MT group will receive emotional nursing care and individualised receptive MT for 1 week, whereas patients in the NMT group will receive emotional nursing care alone. Primary outcomes will include scores on the State-Trait Anxiety Inventory, Distress Thermometer and Hamilton Anxiety Scale. Secondary outcomes will include scores on the Quality of Life Questionnaire C30, serum concentrations of the cytokines interleukin (IL)-1ß, tumour necrosis factor-α, IL-2R, IL-4, IL-6, IL-8 and IL-10, serum concentrations of the neurotransmitters 5-hydroxytryptamine, dopamine, norepinephrine, adrenocorticotropic hormone and γ-aminobutyric acid, and determination of gut microbiota populations. ETHICS AND DISSEMINATION: On 5 August 2020, the study protocol was approved by the Research Ethics Committee of the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine of the Shanghai University of Traditional Chinese Medicine. The findings of this study will be published in peer-reviewed publications and presented at appropriate conferences. TRIAL REGISTRATION NUMBER: CTR2000035244.
Subject(s)
Music Therapy , Neoplasms , Humans , Quality of Life , China , Anxiety/therapy , Neoplasms/complications , Neoplasms/therapy , Cytokines , Randomized Controlled Trials as TopicABSTRACT
Feiyanning Formula (FYN), a Chinese herbal formula derived from summarized clinical experience, is proven to have anti-tumor effects in lung cancer patients. Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), can improve progression-free survival and overall survival of patients but drug resistance is inevitable. The current study evaluated the effects of FYN in osimertinib-resistant HCC827OR and PC9OR cells. FYN preferentially inhibited the proliferation and migration of HCC827OR and PC9OR cells. Moreover, FYN and osimertinib exhibited synergistic inhibitory effects on proliferation and migration. Real-time qPCR (RT-qPCR) and western blotting results indicated that FYN downregulated gene and protein levels of GSK3ß and SRFS1, which are enriched in the Wnt/ß-catenin pathway. Besides, FYN inhibited tumor growth and exhibited synergistic effects with osimertinib in vivo. Collectively, the results suggested that FYN exerted an anti-osimertinib resistance effect via the Wnt/ß-catenin pathway.
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Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) significantly improve the prognosis of non-small cell lung cancer (NSCLC) with EGFR mutation-positive. Although third-generation EGFR-TKI osimertinib is demonstrated with superior efficacy compared with first-generation EGFR-TKIs, acquired resistance to EGFR-TKIs remains the bottleneck. The Chinese herbal medicine (CHM) Yiqi-Yangyin-Jiedu decoction (YYJD) has been shown to delay acquired resistance to first-generation EGFR-TKIs in the CATLA study, but there is no high-level evidence for its effect when combined with osimertinib. This trial aims to evaluate the efficacy and safety of YYJD combined with osimertinib as first-line treatment in EGFR mutation-positive advanced NSCLC. Methods: This is a double-blind, multi-center, randomized controlled trial conducted in eight hospitals in China. A total of 314 participants will be randomly assigned to the osimertinib plus YYJD group (O+YYJD) or the osimertinib plus placebo group (O+placebo). Treatment will last until disease progression or death. Patients diagnosed with advanced NSCLC harboring EGFR Ex19del or L858R will be enrolled if they are ready to take osimertinib as first-line treatment, aged 18-74 years old, and provide signed informed consent. The primary outcome is progression-free survival (PFS). The secondary outcomes include a comparison of overall survival (OS), objective response rate (ORR), disease control rate (DCR), and quality of life (QoL). The analysis will be based on intention-to-treat and per-protocol subject analysis principles. Discussion: The goal of this trial is to evaluate the efficacy and safety of YYJD when added to osimertinib as first-line treatment in EGFR mutation-positive advanced NSCLC.
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OBJECTIVE: To observe the clinical efficacy of blade acupuncture combined with functional exercise for chronic pain after non-small cell lung cancer surgery. METHODS: A total of 62 patients with chronic pain after surgery for non-small cell lung cancer were randomly divided into an observation group and a control group, 31 cases in each group. The patients in the control group were treated with functional exercise. On the base of the treatment in the control group, the patients in the observation group were treated with blade acupuncture at the tendon nodes or painful points, once a week for 4 weeks. The visual analogue scale (VAS) scores of pain before treatment and day 1, day 7, day 14, day 28 of treatment and day 90, day 180 when follow up were compared between the two groups; the brief pain inventory (BPI) scores before and after treatment were compared between the two groups. RESULTS: The VAS score in the observation group at each time point after treatment was lower than that before treatment (P<0.01), and lower than that in the control group (P<0.01). Compared before treatment, the daily life score, emotion score, walking ability score, sleep score and life enjoyment score and total score of BPI in the observation group were reduced after treatment (P<0.05), and the daily life score, emotion score, sleep score and total score of BPI in the observation group were lower than those in the control group (P<0.05). CONCLUSION: The blade acupuncture combined with functional exercise could effectively alleviate the chronic pain after non-small cell lung cancer surgery, improve the quality of life of patients, and the effect is lasting and stable.
Subject(s)
Acupuncture Therapy , Carcinoma, Non-Small-Cell Lung , Chronic Pain , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/surgery , Chronic Pain/etiology , Chronic Pain/therapy , Quality of Life , Acupuncture Points , Lung Neoplasms/complications , Lung Neoplasms/surgery , Treatment OutcomeABSTRACT
Xiaoxianxiong Tang (XXXT) is a well-known traditional Chinese medicine formula. Evidence is emerging supporting the benefits of XXXT in ameliorating therapy for non-small cell lung cancer (NSCLC). The purpose of this study aimed to explore the effects and mechanisms of XXXT through network pharmacological analysis and biological validation. TCMSP database was used to identify potentially active compounds in XXXT with absorption, distribution, metabolism, excretion screening, and their potential targets. The disease targets related to NSCLC were predicted by searching for Therapeutic Target database, GeneCards database, DrugBank database, and DisGeNET database. Of the 4385 NSCLC-related targets, 156 targets were also the targets of compounds present in XXXT. Subsequently, GO function and KEGG pathway enrichment and PPI network analyses revealed that, of the 95 targets and 20 pathways influenced by 20 ingredients in XXXT, 20 targets were associated with patient survival, and XXXT could exert an inhibitory action on the PI3K-AKT signaling pathway. Moreover, XXXT restrained the proliferation of A549 and H460 cells in a concentration-dependent manner and suppressed the mRNA and protein levels of key targets CCNA2, FOSL2, and BIRC5 closely linked to the PI3K-AKT pathway. Hence, XXXT has the potential to improve therapy for NSCLC by targeting the PI3K-AKT signaling pathway.
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Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. First-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) significantly improve prognosis of advanced NSCLC patients harboring EGFR sensitizing mutation. However, acquired resistance to EGFR-TKIs limits the good outcomes. Chinese herbal medicine (CHM) has been used for NSCLC patients receiving EGFR-TKIs for more than 10°years as an adjuvant treatment. Methods: Studies were searched from China BioMedical Literature, Chinese National Knowledge Infrastructure, Cqvip Database, Wanfang Database, MEDLINE (PubMed), EMBASE (Ovid), Google Scholar, and Cochrane Library from inception to March, 2021. Randomized controlled clinical trials (RCT) comparing EGFR-TKIs + CHM (TKIs + CHM) versus EGFR-TKIs with/without placebo (TKIs ± placebo) in participants with advanced NSCLC harboring EGFR sensitizing mutation were included in this study. Two authors screened all references, assessed the risk of bias and extracted data independently. Data were summarized using hazard ratio (HR) and risk ratios (RR), with 95% confidence intervals (CI) for binary outcomes. Meta-analysis was performed using random effects model. Overall quality of evidence was assessed using GRADE. Results: A total of 9 RCTs (1137 participants, 581 in the TKIs + CHM group and 556 in the TKIs ± placebo group) were included in this review. Only first-generation EGFR-TKIs were included. Most trials included used oral CHM preparations to tonify Qi and/or Yin. Treatment lasted from enrollment until disease progression (PD) or intolerable adverse events (AE). Combination of CHM with EGFR-TKIs improved median progression-free survival (mPFS) (HR,0.59; 95% CI, 0.52-0.68; P < 0.00001) and objective response rate (ORR) (RR, 1.23; 95% CI, 1.13-1.34; P < 0.00001) compared with used of EGFR-TKIs ± placebo. CHM reduced AE associated with EGFR-TKIs such as cutaneous toxicity (RR, 0.58; 95% CI, 0.46-0.73; P < 0.00001) and diarrhea (RR, 0.43; 95% CI, 0.30-0.60; P < 0.00001). Conclusion: Combination therapy of CHM and EGFR-TKIs significantly delays acquired resistance while improving ORR to EGFR-TKIs. Furthermore, CHM reduces AE induced by EGFR-TKIs. More international multi-centered, double-blinded, placebo-controlled, well-designed clinical trials are needed in future research.
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The paper reports the experiences in treatment of two cases of corona virus disease 2019 (COVID-19) with the combination of acupuncture and medication in bedridden patients confirmed in C7 Inpatient Ward, Wuhan Leishenshan Hospital, China. The combined treatment of acupuncture with the oral administration of "Shanghai leishen No.1 formula" was given every day. The prescription was modified weekly according the symptoms of the patients. Besides, the antivirus, anti-infectious and symptomatic treatment of western medicine was combined. Both of the two cases were improved and discharged. It is anticipated that the treatment experiences in these two cases may provide the instruction and enlightenment for the prevention and treatment of COVID-19.
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BACKGROUND: Comprehensive rehabilitation therapy based on traditional Chinese medicine (TCM) has been widely applied in various cancer treatments in China. Thus far, Chinese herbal medicine (CHM) has been shown effective in reducing the adverse effects of chemotherapy and improving the quality of life (QoL) during chemotherapy. The purpose of the present study is to compare the effects of CHM plus Liu Zi Jue (LZJ) exercises with CHM plus rehabilitation education and with placebo plus rehabilitation education in patients who have undergone complete resection for nonsmall-cell lung cancer (NSCLC) followed by postoperative adjuvant chemotherapy. METHODS AND DESIGN: A multicenter, randomized clinical trial will be performed with 354 stage Ib-IIIa NSCLC patients in five centers in China. Patients satisfying the inclusion criteria will be randomly divided into three groups according to a 1:1:1 ratio: intervention group A (IGA), intervention group B (IGB), and control group (CG). Each group will receive adjuvant platinum-based doublet chemotherapy for a total of four cycles. IGA participants will receive chemotherapy combined with CHM and LZJ exercises, IGB participants will receive chemotherapy combined with CHM and rehabilitation education, and CG participants will receive chemotherapy combined with placebo and rehabilitation education. The herbal treatment patients will be given granules daily and LZJ exercises will be performed four times per week during chemotherapy. The primary outcome is QoL, which will be assessed with the European Organization for Research and Treatment of Cancer (EORTC)-QLQ-C43 scale in each cycle. The secondary outcomes include the 2-year disease-free survival rate, disease-free survival, TCM symptoms, tumor markers, safety, and adverse events. After treatment, the patients will be followed up every 3 months within 2 years and every 6 months after 2 years until disease recurrence and/or metastasis. DISCUSSION: Our previous study reported that CHM in combination with chemotherapy could lower the overall incidence of adverse events but increased digestive and gastrointestinal side effects compared with chemotherapy alone in postoperative NSCLC patients. This study will lay a foundation for the effectiveness of chemotherapy with or without a comprehensive rehabilitation program for QoL in patients with postoperative NSCLC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03372694. Retrospectively registered on 17 December 2018.
Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/rehabilitation , Drugs, Chinese Herbal/therapeutic use , Exercise Therapy/education , Lung Neoplasms/drug therapy , Lung Neoplasms/rehabilitation , Antineoplastic Agents, Phytogenic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols , Biomarkers, Tumor , Chemotherapy, Adjuvant , China , Clinical Trials, Phase III as Topic , Disease-Free Survival , Humans , Multicenter Studies as Topic , Postoperative Period , Quality of Life , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: The toxicity and side effects caused by adjuvant chemotherapy (ACT) after radical surgery for lung adenocarcinoma (LAC) lead to early termination frequently. This study was conducted to provide an objective basis for the effect of Chinese herbal medicine formulas (CHMFs) combined with chemotherapy in reducing toxicity and enhancing efficacy of ACT. METHOD: From February 17th, 2012 to March 20th, 2015, 233 patients from 7 hospitals diagnosed with LAC in IB~IIIA stage were randomly assigned into ACT + CHMF group (116 patients) and ACT + placebo group (117 patients). CHMF was taken orally until the end of chemotherapy. Chemotherapy-related toxic, side effects were investigated as the primary outcome. Disease-free survival (DFS) and overall survival (OS) were used as the secondary outcome. RESULTS: At one week following chemotherapy, the incidence of dry mouth, diarrhea and thrombocytopenia significantly decreased in CHMF group (P = 0.017, P = 0.033, P = 0.019, respectively). At two weeks following chemotherapy, fatigue and diarrhea were more obvious in the placebo group (P = 0.028, P = 0.025, respectively). In addition, patients in the CHMF group showed an increase in median DFS from 37.1 to 51.5 months compared with placebo group although there was no statistical significance (P = 0.16). In the stage IB subgroup, the CHMF group had a significantly better DFS (HR (95% CI) = 0.53 (0.28-0.99), P = 0.046). There was no significant difference in OS between the groups (P = 0.72). CONCLUSION: For patients with LAC, ACT combined with CHMF after radical surgery can prolong the DFS time especially in the early stage, and reduces the chemotherapy-related toxic and side effects. TRIAL REGISTRATION: NCT01441752. Registered 14 July, 2011.
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Although osimertinib, an EGFR tyrosine kinase inhibitor, has become the standard therapy for treating non-small cell lung cancer (NSCLC) patients with EGFR-activating mutation, upregulation of MCL-1 induces acquired resistance to osimertinib. Bufalin, a natural digoxin-like ingredient isolated from a traditional Chinese medicine Chan Su, has been shown to downregulate MCL-1 in NSCLC cells. However, whether bufalin reverses this acquired resistance to osimertinib in NSCLC cells remains unclear. In this study, bufalin reduced cell viability and promoted apoptosis in osimertinib-resistant cells. Moreover, co-treatment with bufalin and osimertinib restored the sensitivity of osimertinib-resistant cells to osimertinib-induced growth regression and apoptosis in vitro and in vivo. Mechanistically, MEK/ERK-dependent MCL-1 phosphorylation and Ku70-mediated MCL-1 overexpression confer osimertinib resistance in EGFR-mutant NSCLC cells. In osimertinib-resistant cells, bufalin modulates Ku70-mediated MCL-1 degradation, but not MEK/ERK/MCL-1 signaling. In conclusion, our study suggests that bufalin eliminates resistance to osimertinib by inhibiting Ku70-mediated MCL-1 overexpression, indicating that a combination of osimertinib and bufalin could be an effective additional treatment to overcome acquired resistance to osimertinib in NSCLC cells.
Subject(s)
Acrylamides/therapeutic use , Aniline Compounds/therapeutic use , Antineoplastic Agents/therapeutic use , Bufanolides/pharmacology , Carcinoma, Non-Small-Cell Lung/drug therapy , Genes, erbB-1/genetics , Lung Neoplasms/drug therapy , Myeloid Cell Leukemia Sequence 1 Protein/metabolism , Animals , Bufanolides/therapeutic use , Carcinoma, Non-Small-Cell Lung/genetics , Drug Resistance, Neoplasm/drug effects , Fluorescent Antibody Technique , In Situ Nick-End Labeling , Lung Neoplasms/genetics , Male , Mice, Inbred BALB C , Mice, Nude , Neoplasm TransplantationABSTRACT
Background: To determine the clinical activity and safety of Chinese herbal medicine (CHM) combined with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) in patients with advanced pulmonary adenocarcinoma (ADC) and the ability of CHM combined with EGFR-TKI to activate EGFR mutations. Methods: Three hundred and fifty-four patients were randomly assigned to EGFR-TKI (erlotinib 150 mg/d, gefitinib 250 mg/d, or icotinib 125 mg tid/d) plus CHM (TKI+CHM, N = 185) or EGFR-TKI plus placebo (TKI+placebo, N = 169). Progression-free survival (PFS) was the primary end point; the secondary end points were overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life [Functional Assessment of Cancer Therapy-Lung (FACT-L) and Lung Cancer Symptom Scale (LCSS)], and safety. Results: The median PFS was significantly longer for the TKI+CHM group (13.50 months; 95% CI, 11.20-16.46 months) than with the EGFR-TKI group (10.94 months; 95% CI, 8.97-12.45 months; hazard ratio, 0.68; 95% CI, 0.51-0.90; P = 0.0064). The subgroup analyses favored TKI+CHM as a first-line treatment (15.97 vs. 10.97 months, P = 0.0447) rather than as a second-line treatment (11.43 vs. 9.23 months, P = 0.0530). Patients with exon 19 deletion had a significantly longer PFS than with 21 L858R. The addition of CHM to TKI significantly improved the ORR (64.32% vs. 52.66%, P = 0.026) and QoL. Drug-related grade 1-2 adverse events were less common with TKI+CHM. Conclusions: TKI+CHM improved PFS when compared with TKI alone in patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01745302.
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Background: Chinese Herb Medicine Formulas (CHMF) was reported to improve the quality of life (QoL) in advanced NSCLC patients. The present study was designed to investigate whether maintenance chemotherapy plus CHMF in patients would improve QoL and progression-free survival (PFS). Methods: Seventy-one patients were enrolled from 8 medical centers in China, and were randomly assigned to a maintenance chemotherapy plus CHMF group (n = 35) or a maintenance chemotherapy plus placebo group (n = 36). The outcome measures included PFS, Karnofsky performance status (KPS) scores, QoL (assessed with the lung cancer symptom scale (LCSS) questionnaire), and adverse events (AEs). Results: Patients in the CHMF group showed significant improvements in median PFS (HR = 0.55, 95% CI 0.28-0.88, P = 0.019), KPS scores (P = 0.047), fatigue (cycle [C] 3: P = 0.03), interference with daily activities (C3: P = 0.04) and dyspnea (C2: P = 0.03) compared with patients in the placebo group. Compared with the placebo group, the incidence of AEs decreased in the CHMF group, including loss of appetite (C2: P = 0.011, C4: P = 0.004) and dry mouth (C4: P = 0.011). Conclusion: The essential finding of our study is that maintenance chemotherapy combined with CHMF may prolong PFS, relieve symptoms, improve QoL and alleviate the side effects.
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BACKGROUND: To evaluate the effect of qi-nourishing essence-replenishing Chinese herbal medicine combined with chemotherapy in survival of advanced non-small-cell lung cancer(NSCLC) patients with essence and qi deficiency. METHODS: A prospective multi-centered randomized controlled study was conducted, and 266 advanced NSCLC patients were enrolled. 126 patients in control group received Vinorelbine plus cisplatin(NP) chemotherapy combined with symptom-oriented Chinese herbs medication(without qi-nourishing essence-replenishing herbs);140 patients in experimental group received NP chemotherapy combined with qi-nourishing essence-replenishing Chinese herbal medication(Kangliu Zengxiao Decoction and modified Feiyanning Decoction, during and after chemotherapy respectively). RESULTS: One patient in control and 2 in experimental group were excluded for failure to complete two cycles of chemotherapy. During follow-up, 17 and 7 patients in control and experimental group were excluded respectively(4 and 4 for taking Gefetinib after disease progression, 4 and 2 for receiving other chemotherapeutic regimens, 9 and 1 for lost to follow-up). 239 patients were included in the final analysis (131 in experimental group and 108 in control). Median overall survival in experimental group was significantly longer than control group (14.87vs.12.97 months,P = 0.027). In experimental and control group, 1-year, 3-year, 5-year, 7-year, and 9-year survival rates were 57% vs. 53%, 17% vs. 8%, 10% vs. 2%, 6% vs. 0%, and 6% vs. 0%, respectively. CONCLUSION: Qi-nourishing essence-replenishing Chinese herbal medicine combined with chemotherapy improves survival of advanced NSCLC patients with essence and qi deficiency.
ABSTRACT
Traditional Chinese medicine (TCM) plays an indispensable role in cancer prevention and treatment. Chinese herbal medicine (CHM) is a key component of TCM and has been practiced for thousands of years. A number of naturally occurring products from Chinese herbs extracts exhibit strong inhibitory properties against carcinogenesis, including CHM single-herb extracts, CHM-derived active components, and CHM formulas (the polyherbal combinations), which regulate JAK/STAT, MAPK, and NF-Ò¡B pathways. The present review aims to report the cancer-preventive effect of CHM with evidence from cell-line, animal, epidemiological, and clinical experiments. We also present several issues that have yet to be resolved. In the future, cancer prevention by CHM will face unprecedented opportunities and challenges.