Multidisciplinary and Comprehensive Chinese Medicine for Advanced Non-Small Cell Lung Cancer Patients: A Retrospective Study of 855 Cases / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of multidisciplinary and comprehensive Chinese medicine (CM) treatments on progression-free survival (PFS) and median survival time (MST) in patients with advanced non-small cell lung cancer (NSCLC) and identify factors that influence progression and prognosis.@*METHODS@#Clinical data of 855 patients with advanced NSCLC who received multidisciplinary and comprehensive CM treatments at Longhua Hospital from January 2009 to December 2018 were retrospectively analyzed. Univariate analysis was performed by the Kaplan-Meier method and log-rank sequential inspection. Multivariate analysis of significant variables from the univariate analysis was performed with Cox regression modeling. Key factors correlated to progression and prognosis were screened out, and a Cox proportional hazard model was established to calculate the prognostic index.@*RESULTS@#The PFS and MST of 855 advanced NSCLC patients were 9.0 and 26.0 months, respectively. The 1-, 2-, 3-, and 5-year survival rates were 79.2%, 54%, 36.2%, and 17.1%, respectively. Gender, pathologic type, and clinical stage were independent prognostic risk factors; surgical history, radiotherapy, treatment course of Chinese patent medicine, intravenous drip of Chinese herbal preparation, duration of oral administration of Chinese herbal decoction (CHD), and intervention measures were independent prognostic protective factors. Gender was an independent risk factor for progression, while operation history and oral CHD administration duration were independent protective factors (all P<0.05). Women with stage IIIb-IIIc lung adenocarcinoma had the best outcomes.@*CONCLUSIONS@#Female patients have lower progression risk and better prognoses than male patients, younger patients have higher progression risk but better long-term prognoses than the elderlys, and patients with lower performance status scores are at lower risk for progression and have better prognoses. Comprehensive CM treatments could significantly reduce progression risk, improve prognosis, and prolong survival time for patients with advanced NSCLC. This treatment mode offers additional advantages over supportive care alone.

Feiji Recipe inhibits the growth of lung cancer by modulating T-cell immunity through indoleamine-2,3-dioxygenase pathway in an orthotopic implantation model / 中西医结合学报

<p><b>OBJECTIVE</b>Escape from the body's immune response is a basic characteristic of lung cancer, and indoleamine-2,3-dioxygenase (IDO) plays a key role in mediating immune escape of non-small-cell lung cancer, which leads to recurrence and metastasis. Feiji Recipe, a compound Chinese herbal medicine, has the effect of stabilizing lesions and prolonging survival in patients with lung cancer. The purpose of this study was to investigate the mechanisms underlying the anticancer properties of Feiji Recipe.</p><p><b>METHODS</b>An orthotopic transplant model of mouse Lewis lung cancer, with stable expression of IDO gene, was established in C57BL/6 mice. Optical imaging was used to observe the effects of Feiji Recipe in the treatment of lung cancer in vivo. The effects of Feiji Recipe on the proliferation of mouse Lewis lung cancer cell line 2LL, 2LL-enhanced green fluorescent protein (2LL-EGFP) and 2LL-EGFP-IDO were investigated, and the apoptosis of T-cells was examined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide using flow cytometry. Chemical composition of Feiji Recipe was validated by high-performance liquid chromatography.</p><p><b>RESULTS</b>Compared to the control group, the survival of animals treated with Feiji Recipe was significantly prolonged (P = 0.0074), and the IDO protein level decreased (P = 0.0072); moreover, the percentages of CD4CD25 T-cells and Foxp3 T-cells were significantly decreased (P < 0.05). The molecular mechanism of Feiji Recipe against lung cancer may relate to the regulation of immune cells, such as T-cells and regulatory T-cells.</p><p><b>CONCLUSION</b>The molecular mechanism of Feiji Recipe in treatment of lung cancer is to restore the function of T-cells in the cancer microenvironment through interfering with the IDO pathway.</p>

Inhibitory Effect of Feiji Recipe on IDO Induced Immune Escape on the Murine Model of Lewis Lung Carcinoma / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of Feiji Recipe (FR) intervening indoleamine 2,3-dioxygenase (IDO) induced immune escape on the murine model of Lewis lung carcinoma. Methods Totally 48 C57BL/6 mice inoculated with Lewis lung cancer cells transfected with human (enhanced green fluorescent protein,EGFP)-IDO gene were divided into four groups according to radom digit table, i.e., the model group (administered with normal saline by gastrogavage) , the Chinese medicine group (treated with FR Decoction at the daily dose of 100 mg/g by gastrogavage), the 1-methyl-D-trytaphan (1-MT) group (administered with 1-MT mixed liquor at the daily dose of 100 mg/kg by gastrogavage), and the Paclitaxel group (treated with Paclitaxel at the daily dose of 15 mg/kg by peritoneal injection), 12 in each group. The intervention was started from the 2nd day of modeling. The survival time was observed in 24 of them. Ratios of CD4+ CD25+ FoxP3+ regulatory T cells (Treg) in the spleen were detected in the rest 24 mice by flow cytometry respectively.</p><p><b>RESULTS</b>Compared with the model group, the survival time was significantly prolonged in the Chinese medicine group and the 1-MT group (P < 0.01); ratios of Treg cells remarkably decreased in the Chinese medicine group, the 1-MT group, and the Paclitaxel group (P < 0. 01). Compared with the Paclitaxel group, the survival time was significantly prolonged in the Chinese medicine group and the 1-MT group (P < 0.01); ratios of Treg cells decreased significantly in the 1-MT group (P < 0.05).</p><p><b>CONCLUSION</b>FR could inhibit the proliferation of lung cancer cells and immune eseape, improve the immune function, and prolong the survival of tumor-bearing mice.</p>

Treatment of Radical Resected NSCLC by Chinese Medicine Combined with Adjuvant Chemother- apy: a Clinical Study / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of Chinese medicine (CM) combined adjuvant chemotherapy in postponing relapse and metastasis of radical resected Ib-IIIa stage non-small cell lung cancer (NSCLC) patients, and to explore its effect in improving their quality of life (QOL) and clinical symptoms.</p><p><b>METHODS</b>We designed a cohort study of 336 radical resected Ib-IIIa NSCLC patients by analyzing disease free survival (DFS) using Log-rank test. They were randomly assigned to the control group (155 cases, treated by adjuvant chemotherapy group) and the test group (181 cases, treated by adjuvant chemotherapy combined CM). By using controlled method, 60 radical resected NSCLC patients undergoing NP/NC program in 2012 (vinorelbine 25 mg/m2, combined with cisplatin 75 mg/m2 on day 1 and day 8/on day 1 or on day 1, 2, and 3; or carboplatin AUC = 5 on day 1) were assigned to the control group (29 cases) and the test group (31 cases). QOL scores (using EORTC QLQ-LC43 questionnaire) and TCM symptoms scores were compared between the two groups before chemotherapy, peri-chemotherapy (one day before the 2nd course of chemotherapy) , and after chemotherapy (20 days after ending the 4th course of chemotherapy).</p><p><b>RESULTS</b>(1) The median DFS was longer in the test group than in the control group, but with no statistical difference between the two groups (42.73 months vs 35.57 months , P = 0.179). In the subgroup analysis, there was statistical difference in IIIa stage DFS. The median IIIa stage DFS of was longer in the test group than in the control group with statistical difference (27.87 months vs 19. 93 months, P = 0.047). (2) In the control study, repeated measured data indicated there was significant difference in physical functions between the two groups (P < 0.05). Total scores for health states decreased more in the test group than in the control group, but with no statistical difference (P > 0.05). Scores for constipation and CM syndrome scores were higher in the test group than in the control group (P < 0.05).</p><p><b>CONCLUSIONS</b>CM had advantages in postponing DFS of radical resected NSCLC patients, especially in IIIa stage. CM could improve their QOL and clinical symptoms during adjuvant chemotherapy.</p>

Chemotherapy in conjunction with traditional Chinese medicine for survival of elderly patients with advanced non-small-cell lung cancer: protocol for a randomized double-blind controlled trial / 中西医结合学报

<p><b>BACKGROUND</b>Traditional Chinese medicine (TCM) is considered an important complementary therapy with beneficial effects for cancer patients. Elderly patients with non-small-cell lung cancer (NSCLC) are a complex patient group with increasing co-morbidity and shrinking physiological reserve, and may derive substantial benefit from the supportive aspects of TCM. Researchers from Shanghai Longhua Hospital found that qi and yin deficiency is a common syndrome in patients with stage III or IV lung cancer. This project was designed to study the combination of single-agent chemotherapy with TCM methods of benefiting qi and yin in elderly patients with advanced NSCLC.</p><p><b>METHODS AND DESIGN</b>This is a double-blind controlled, multi-center, and prospective study with randomly selected participants from elderly NSCLC patients in China. Seventy-six patients who meet the inclusion criteria will be allocated into two groups, which will receive treatments of 3-week single-agent chemotherapy with TCM or placebo for four cycles. Progression-free survival (PFS) is the primary end point, and the secondary end points are overall survival, objective response rate, time-to-progression, and quality of life (EORTC QLQ-LC43, and TCM syndrome score). Meanwhile, other end points such as toxicity, side effects and safety of the treatments will be assessed.</p><p><b>DISCUSSION</b>Results from this study may provide evidence on the effectiveness, and parameters for the usage of single-agent chemotherapy combined with or without TCM on PFS of elderly patients with NSCLC.</p><p><b>TRIAL REGISTRATION</b>ClinicalTrials.gov. (Identifier: NCT01780181).</p>