VINDESINE WITH CYCLOPHOSPHAMIDE-EPIRUIBIN-CISPLATININ THE TREATMENT LOCALLY ADVANCED NON-SMALCELL LUNG CANCER

Objective: To evaluate the addition of vindesine to acyclophosphamide-epirubicin-cisp (CAP) regimenfor treating the patients with locally advanced non-smallcell lung cancer (NSCLC). Methods: From May 1994to August 1998, 59 previously untreated patients withstage IIIa and IIIb non-small cell lung cancer wereenrolled into this trial. Patients characteristics were thefollowing: the median age was 52 years; the medianperformance status was 1; there were 19 stage IIIa and40 stage IIIb; there were 47 adenocarcinoma, 10squamous cell carcinoma and 2 large cell carcinoma. AIIpatients were treated with vindesine (2 mg/m2, on day 1and day 8), cyclophosphamide (0.6/m2, on day 1),epirubicin (40 mg/m2, on day 1) and cisplatin (60 mg/m2,on day 1) every 3 or 4 weeks. Results: Four achieved acomplete response (6.8%), 29 achieved a partialresponse (49.2%), 15 had stable disease, and 10 hadprogressive disease. A clinical improvement was in 45 of59 patients (76.3%). The most frequent major toxiceffects were myelosuppression, nausea and vomiting.Conclusion: The vindesine with CAP regimen was activecombination chemotherapy in patients with locallyadvanced NSCLC accompanied by the limited sideeffects.

Serum MiRNA as Predictive and Prognosis Biomarker in Advanced Stage Non-small Cell Lung Cancer in Indonesia

Background and objective Lung cancer is the most common cause of death in men in the world and in Indonesia where nonsmall cell carcinoma lung cancer(NSCLC) constitutes 85% of all lung cancer cases. The high mortality rate is due to a poor prognosis and is often diagnosed as having advanced stages. If it is known at the initial stage, the prognosis of lung cancer will be better. Prognosis can be predicted with a marker of prognostic biology, one of which is micro RNA(mi RNA). This study aims to prove that serum mi RNA can be predictive biological marker and prognosis in NSCLC patients in Indonesia.Methods This study was cohort retrospective among 52 subjects in "Dharmais" Hospital National Cancer Center. Sample was obtained from patients’ serum. Mi R-34, mi R-148, mi R-155 and mi R-222 serum are measured through Real-Time PCR(q PCR). Data were analyzed and interpreted with descriptive analysis, bivariate analysis(Mann Whitney-U for two type of variables or Kruskal-Wallis for more than two type of variables. Kaplan-Meier analysis was used to know association between characteristic which are sociodemographic, performance status, clinico-pathology, and survival rate in mi RNA expression. Results From this study, mi RNA expression: mi R-34(46.15%), mi R-148(23.08%), mi R-155(40.38%) and mi R-222(32.69%). Performance status score was statistically significant correlation with mi R-148(P=0.049) and mi R-222(P=0.018). High mi R-34 is associated with multiple M1 b metastatic type(P=0.020), cancer cell type(adenocarcinoma, P=0.009) and adenocarcinoma epidermal growth factor receptor(EGFR) mutation(negative, P=0.031). There was a significant correlation between the high mi R-222 as a poor prognosis in advanced stage NSCLC with M1 b metastasis(Median Survival/MS: 27 d, P=0.049) and positive EGFR mutations(MS: 74 d, P=0.049) and correlation of mi R-155 with adenocarcinoma(MS: 69 d, P=0.034) and positive EGFR gene mutations(MS: 58 d, P=0.023).Conclusion High mi R-34 expression in advanced stage NSCLC is the predictive factor for multiple metastatic, adenocarcinoma cell type and adenocarcinoma negative EGFR mutation. High expression of mi R-155 and mi R-222 are poor prognoses, especially high mi R-222 found in metastasis M1 b and positive EGFR mutation and mi R-155 found in adenocarcinoma and positive EGFR gene mutations. Further studies regarding correlation between mi RNA and survival rate are needed.

Nab-paclitaxel(abraxane)-based chemotherapy to treat elderly patients with advanced non-small-cell lung cancer:a single center,randomized and open-label clinical trial

Background： The purpose of this study is to evaluate the clinical efficacy and safety of abraxane-based chemotherapy with/without nedaplatin in elderly patients with non-small-cell lung cancer （NSCLC）. Materials and methods： From October 2009 to January 2013, 48 elderly patients （≥65 years） with NSCLC were investigated in this clinical trial. The patients were randomized and equally allocated into arms A and AP- （A） abraxane （130 mg/m2, days 1, 8）; （B） abraxane ＋ nedaplatin （20 mg/m2 days 1-3, q3w）. The parameters of objective response rate （ORR）, disease control rate （DCR）, progression-free survival （PFS）, overall survival （OS） and side effects were evaluated between two arms. Results： Over 80% of the patients completed four cycles of chemotherapy. The total ORR was 21.3 %, DCR was 55.3%, PFS 4.5 months and OS 12.6 months. No significant difference was found between arms A and AP in terms of ORR （16.7% vs. 26.1%, P=0.665） or DCR （55.3% vs. 56.5%, P=0.871）. The median PFS in arm A was 3.3 months [25-75% confidence interval （CI）： 3.1-7.2] and 5.5 months （25-75% CI： 3.2-7.0） in arm AP with no statistical significance （P=0.640）. The median OS in arm A was 12.6 months （25-75% CI： 5.7-26.2） and 15.1 months （25-75% CI： 6.4-35.3） in arm AP with no statistical significance （P=0.770）. The side effects were mainly grade 1-2. The incidence of grade 3-4 toxicities was 29.1% in arm A and 62.5% in arm AP with a statistical significance （P=0.020）. Conclusions： Compared with combined therapy, abraxane alone chemotherapy was beneficial for elderly NSCLC patients with better tolerability and less adverse events, whereas did not significantly differ in terms of ORR, DCR, PFS or OS.

Oncothermia in Combination with Vitamin C Infusion for Non-small Cell Lung Cancer: a Case Report

We herein report an advanced case(T3N3M0,Stage ⅢB)of squamous cell lung cancer.The patient survived beyond 5 years only receiving intravenous vitamin C(VitC)infusion combined with modulated electrohyperthermia(mEHT,trade name:oncothermia).

Feasibility of cetuximab and chemoradiotherapy combination in Chinese patients with unresectable stage Ⅲ non-small cell lung cancer:a preliminary report

Objective： In recent years, the combination of cetuximab and chemoradiotherapy （CRT） has been used to treat stage III non-small cell lung cancer （NSCLC）; however, limited data are available for Chinese patients. Herein, we report preliminary data from a phase I/II study testing the combination of cetuximab with inductive chemotherapy, followed by concurrent CRT （CCRT） in Chinese patients with stage III NSCLC. Methods： Eligibility criteria were Zubrod performance status （PS） 0-1, forced expiratory volume in 1 second （FEV1） 〉_1.2 L and adequate organ function. Enrolled patients received weekly cetuximab （initial dose of 400 mg/m2 on day 1 of week 1 and a maintenance dose of 250 mg/m2 on week 2 to the end of CCRT） with cisplatin/vinorelbine （NP） chemotherapy （every 3 weeks for 2 cycles from week 2, followed by two cycles of concomitant NP chemotherapy and intensity-modulated thoracic radiotherapy （TRT） （60-66 Gy/2 Gy）. The primary endpoints were toxicity and feasibility. All patients received positron emission tomography- computerized tomography （PET-CT） scans within the 2 weeks prior to enrollment. Univariate analyses were used to assess the correlation between SUV-T, SUV-N, SUV-TOTAL, gender, age, histology, tumor-node- metastasis （TNM） stage, PS and smoking status and survival. Survival curves were generated for different populations using the Kaplan-Meier method and compared using a log-rank test. Results： Seventeen patients were enrolled and 16 completed the full regime. The overall response rate （ORR） was 58.8% and 82.3% after the induction and CCRT phases, respectively. With a median follow-up duration of 27.6 months, the median survival was 27.6 months [95% confidence interval （CI）： 11.3-43.9 months] with 1- and 2-year survival rates of 88.2% （95% CI, 60.6-96.9%） and 58.8% （95% CI, 60.6-77.8%）, respectively. Three patients remain progression-free to date, and the median progression-free survival （PFS） was 13.5 months （95% CI, 6.8-20.2 months）. No treatment-related death occurred; however, 76% of the patients experienced grade 3＋ adverse events （AEs）, including nansea/vomiting, intestinal obstruction, and esophagitis （〈6%）, while other AEs were mostly of hematological nature （71%）. The cut-off values for SUV-T and SUV-TOTAL were 11 and 20, respectively. Univariate analyses revealed SUV-TOTAL （P=0.027）, SUV-T （P=0.025）, and PS （P=0.006） as potential survival predictors, with a hazard ratio （HR） of 3.4, 3.7, and 9.9, respectively. Conclusions： The combination of cetuximab with induction chemotherapy followed by CCRT appears feasible and promising. Local and locoregional maximal SUVs, defined by 18F-FDG PET-CT scanning, may represent a prognostic indicator for long-term survival for these patients, which warrants further study.

Peripheral CD4^(+) T cell signatures in predicting the responses to anti-PD-1/PD-L1 monotherapy for Chinese advanced non-small cell lung cancer

Limited benefit population of immune checkpoint inhibitors makes it urgent to screen predictive biomarkers for stratifying the patients.Herein,we have investigated peripheral CD4^(+) T cell signatures in advanced non-small cell lung cancer(NSCLC)patients receiving anti-PD-1/PD-L1 treatments.It was found that the percentages of IFN-γand IL-17A secreting naïve CD4^(+) T cells(Tn),and memory CD4^(+) T cells(Tm)expressing PD-1,PD-L1 and CTLA-4 were significantly higher in responder(R)than non-responder(NonR)NSCLC patients associated with a longer progression free survival(PFS).Logistic regression analysis revealed that the baseline IFN-γ-producing CD4^(+) Tn cells and PD-1^(+)CD4^(+) Tm cells were the most significant signatures with the area under curve(AUC)value reaching 0.849.This was further validated in another anti-PD-1 monotherapy cohort.Conversely,high percentage of CTLA-4^(+)CD4^(+) Tm cells was associated with a shorter PFS in patients receiving anti-PD-L1 monotherapy.Our study therefore elucidates the significance of functional CD4^(+) Tn and Tm subpopulations before the treatment in predicting the responses to anti-PD-1 treatment in Chinese NSCLC patients.The fact that there display distinct CD4^(+) T cell signatures in the prediction to anti-PD-1 and anti-PD-L1 monotherapy from our study provides preliminary evidence on the feasibility of anti-PD-1 and anti-PD-L1 combination therapy for advanced NSCLC patients.