Adjuvant Chemotherapy with Chinese Herbal Medicine Formulas Versus Placebo in Patients with Lung Adenocarcinoma after Radical Surgery: a Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

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.

Maintenance Chemotherapy With Chinese Herb Medicine Formulas vs. With Placebo in Patients With Advanced Non-small Cell Lung Cancer After First-Line Chemotherapy: A Multicenter, Randomized, Double-Blind Trial.

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.

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.

Enhanced oral bioavailability of salmeterol by loaded PLGA microspheres: preparation, in vitro, and in vivo evaluation.

The objective of the current study was to prepare microspheres of salmeterol (SM) using poly (lactide-co-glycolide) (PLGA) and assess its viability to enhance the oral bioavailability. Microspheres of SM were prepared by oil-in-water emulsion-solvent evaporation method. The formulations were characterized in encapsulation efficiency, particle size, zeta potential, and in vitro release. The prepared microspheres were found to be spherical in shape with smooth surface. The size of microspheres ranged from 14.7 to 16.5 µm. The polydispersity index (PDI) was 0.12 ± 0.05 and the zeta potential was -33.2 ± 1.4 mV. In vitro release profile, SM was graduated released from the microspheres as time lapsed, suggesting that SM was well entrapped in SM-loaded PLGA microspheres. The model that fitted best for SM released from the microspheres was Higuchi equation. In vivo study, SM-loaded PLGA microspheres are thought to have the potential to maintain SM concentration within target ranges for a long time, decreasing side effects caused by concentration fluctuation, ensuring the efficiency of treatment and improving patient compliance by reducing dosing frequency.