Combined Treatment with JFKD and Gefitinib Overcomes Drug Resistance in Non-Small Cell Lung Cancer.

BACKGROUND: Gefitinib is an important drug used to treat Non-Small Cell Lung Cancer (NSCLC) with EGFR activating mutations, but drug resistance restricts its clinical application. In this present study, combined Jin Fu Kang Decoction (JFKD) and gefitinib showed specific cytotoxicity to gefitinib-resistant cancer cells (PC-9/gef). OBJECTIVE: This study aimed to decipher the molecular mechanism of the JFKD on drug resistance when used together with Gefitinib and to find the contributing bio-active substance(s) in JFKD based on the putative mechanism. METHODS: To investigate the combined effect of gefitinib and JFKD, in vitro experiments were conducted on the established gefitinib-resistant PC-9 subclone, while in vivo experiments were conducted on the BALB/c nude mice with PC-9/gef xenografts. Western blot was used to evaluate the protein expression, and Ultra-Performance Liquid Chromatography (UPLC) coupled with quadrupole time-offlight Mass Spectrometry (MS) was used to detect the bio-active compounds of JFKD. RESULTS: The expression of the PTEN-relevant protein p-EGFR, p-Akt in vitro was inhibited more when combined JKFD and gefitinib were used, whereas the activities of PDCD4 and PTEN were increased; remarkably, in vivo experiments showed enhanced tumor growth inhibition when treated with this combination. Due to this combination, the effect on the gefitinib-resistant cell line, one of the JFKD-induced anti-cancer mechanisms, was found. To link the putative mechanism and the anticancer compounds in JFKD, 14 saponins and flavonoids were detected. CONCLUSION: The results suggested that a promising TCM-participated therapy can be established by the putative mechanism of the combined treatment in resistant NSCLC and screening the contributing bio-active substance(s) in JFKD is meaningful on new TCM formula discovery.

Chinese Herbal Medicine Combined With EGFR-TKI in EGFR Mutation-Positive Advanced Pulmonary Adenocarcinoma (CATLA): A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

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.

Effects of Chinese Medicine as Adjunct Medication for Adjuvant Chemotherapy Treatments of Non-Small Cell Lung Cancer Patients.

The aim was to evaluate the effects of traditional Chinese medicine (TCM) as a combination medication with adjuvant chemotherapy on postoperative early stage non-small cell lung cancer (NSCLC) patients. The 314 patients with completely resected stage IB, II or IIIA cancers were assigned into vinorelbine plus cisplatin/carboplatin (NP/NC) (control, n = 158) and NP/NC with additional TCM (intervention, n = 156) groups. The primary endpoint was QOL scores; secondary endpoints were the toxicity and safety of the regimens. The NP/NC regimen caused mild (grade 1 or 2) non-hematologic toxic effects in the patients comprising vomiting (43.6%), fatigue (36.9%), pain (23%), dry mouth (27.6%) and diarrhea (7.9%). The incidence of adverse events was significantly lower in the intervention group than in the control group (0.57% vs 4.02%, P = 0.037). Transient severe (grade 3 or 4) hematological toxic effects occurred less often (hemoglobin reduction (11.9 vs 22.5 percent) and total bilirubin increased (to 42.1 vs 46.2%) in the intervention compared to the control group during the 2nd chemotherapy cycle. When combined with adjuvant chemotherapy, TCM led to partial relief of symptoms in addition to a reduction of side-effects and adverse events caused by the NP/NC regimens.

Multi-center randomized double-blind controlled clinical study of chemotherapy combined with or without traditional Chinese medicine on quality of life of postoperative non-small cell lung cancer patients.

BACKGROUND: Traditional Chinese medicine (TCM) is a widely applied complementary therapy for cancer patients. It can reduce the chemical drugs induced toxic effects to improve the quality of life (QOL). This study applies the highest quality of clinical trial methodology to examine the role of TCM in improving QOL of postoperative non-small-cell lung cancer patients. METHODS AND DESIGN: This study is a multi-center, randomized, placebo-controlled, double-blind trial. Four hundred eighty patients will be recruited into seven different research centers in China. These patients that meet the inclusion criteria will be randomized into either a treatment group or a placebo group. Each group will receive treatments of 3-weekly chemotherapy with TCM or placebo for four cycles. The primary outcome will involve the evaluation of QOL and the secondary outcome assessments will include two-year disease-free survival rate and disease-free survival. Other efficacy assessments are changes of TCM symptoms and toxicity. Side effects and safety profile of the therapy would be evaluated at the same time. The investigators expect that TCM therapy combined with chemotherapy is superior to chemotherapy solely in terms of QOL improvement and disease-free survival extension. "Intention-to-treat" analysis will include all randomized participants. DISCUSSION: The results from the clinical trial will provide evidence for the effectiveness of chemotherapy combined with or without TCM in QOL of postoperative NSCLC patients. TRIAL REGISTRATION: Clinical Trials.gov (Identifier: NCT01441752).

[Study on the effect of Feiji Decoction for soothing the liver combined with psychotherapy on the quality of life for primary lung cancer patients].

BACKGROUND AND OBJECTIVE: Lung cancer is the most common type among all malignant tumors, bringing huge pain and mood disorders to patients suffering from it. This study aims to evaluate the effect of the Feiji Decoction for soothing the liver combined with psychotherapy for depression and anxiety on patients with primary lung cancer. It also aims to further explore the relationship between depression and anxiety. METHODS: A total of 118 patients with primary non-small cell lung cancer were randomly divided into two groups. The combined therapy group consisted of 57 patients who were treated with Feiji Decoction for soothing the liver and psychotherapy combined with chemotherapy. The control group consisted of 61 patients who were treated with chemotherapy only. Both groups were observed for two treatment courses. The Zung Self-reported Depression Scales (SDS) and Zung Self-reported Anxiety Scales (SAS) were used to assess the patients' psychology status in both groups before and after treatment scales. RESULTS: After treatment, the depression and anxiety scores of the therapy group remarkably decreased compared with scores before treatment, indicating a statistical significance (P<0.01). In comparison, after treatment, the depression and anxiety scores of the control group significanfly increased compared with scores before treatment, indicating a statistical significance (P<0.01) as well. The depression and anxiety scores of the therapy group significanfly decreased compared with scores of the control group, showing statistical significance (P<0.01). Thus, depression and anxiety score has a close co-relationship, showing significant positive correlation (P<0.01). CONCLUSIONS: Feiji Decoction for soothing the liver combined with psychotherapy can alleviate depression and anxiety in patients with primary lung cancer. This therapy has good clinical therapeutic effect.