Effects of gemcitabine on cell proliferation and apoptosis in non-small-cell lung cancer (NSCLC) cell lines

We evaluated the antiproliferative and the proapoptotic ability of gemcitabine in three non-small-cell lung cancer (NSCLC) cell lines. NCI-H292 (mucoepidermoid carcinoma), NCI-CorL23 (large-cell carcinoma) and NCI-Colo699 (adenocarcinoma) cells were cultured with and without 0.5, 0.05 and 0.005 μM gemcitabine for 24, 48 and 72 h, respectively. Gemcitabine exerted a stronger and earlier antiproliferative and proapoptotic effect on H292 cells than on CorL23 or Colo699 cells. Fas receptor expression was increased in all three cell lines and was higher in Colo699 than in CorL23 cells. The incubation of NSCLC with anti-Fas agonistic monoclonal antibody (CH11) induced cell apoptosis in H292 cells, demonstrating that the Fas receptor was functionally active. Finally, gemcitabine and CH-11 exerted a synergistic effect on cell apoptosis in H292 cells. This study demonstrates that gemcitabine induces apoptosis in NSCLC and that this effect might be exerted by modulating functionally active Fas expression, and these effects of gemcitabine were stronger in H292 cells than in either CorL23 or Colo699 cells. Received: 24 March 1999 / Accepted: 25 July 2000     

Blood telomerase activity and its correlativity with non-small cell lung carcinoma

From the viewpoint of oncology, an importantcharacteristic of cancer is that cell schizogenesisbecomes out of control[1,2]. Recently, lots of researchesfocus on telomerase. The activation of telomerase isessential for cell to get athanasia, which is the key step incancer pathogenesis, while the normal cell lacks suchenzyme activity[3-5]. Thus, telomerase theory for cancerpathogenesis occurred. Lung cancer is a malignant disease with highincidence, which increases rapidly with theindustrializat…     

Gefitinib in elderly and unfit patients affected by advanced non-small-cell lung cancer

Elderly and poor performance status advanced non-small-cell lung cancer (NSCLC) patients often tolerate chemotherapy poorly. Special approaches are needed for these patient populations. Gefitinib (Iressa) was used in 59 elderly and/or unfit NSCLC pretreated patients participating in a compassionate use programme showing some activity and good tolerability.     

Location Matters: Stage I Non–Small-cell Carcinomas of the Lower Lobes Treated With Stereotactic Body Radiation Therapy Are Associated With Poor Outcomes

IntroductionThe lung is a heterogeneous organ with relative overperfusion of the lung bases. We determined whether a lower lobe primary tumor location was associated with poor outcomes in the setting of stage I non–small-cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT).Patients and MethodsThe data from consecutive patients with stage I NSCLC treated from 2009 to 2014 with curative intent SBRT were analyzed. Primary tumors in the right and left lower lobes were compared against the tumors in all other locations to determine whether a lower lobe location was associated with worse local, regional, and distant control and worse relapse-free and overall survival. The survival rates were estimated using Kaplan-Meier analysis, and multivariate analysis was completed using the Cox proportional hazards model, adjusting for age, stage, performance status, and radiation dose.ResultsA total of 122 patients with early-stage NSCLC who underwent SBRT were evaluated at a median follow-up period of 28.6 months. On multivariate analysis, lower lobe tumors were associated with poor relapse-free survival (hazard ratio [HR], 2.78; 95% confidence interval [CI], 1.21-7.76; P = .04) and poor overall survival (HR, 2.33; 95% CI, 1.09-5.64; P = .04). The 3-year relapse-free survival for patients with a lower lobe primary was 75% compared with 89% for patients with a non–lower lobe primary (P = .04). Additionally, the 3-year overall survival rate for patients with a lower lobe primary was 63% versus 82% in patients with a non–lower lobe primary (P = .01).ConclusionLower lobe stage I NSCLC tumors treated with SBRT are associated with poor relapse-free and overall survival.     

The Impact of Baseline Edmonton Symptom Assessment Scale Scores on Treatment and Survival in Patients With Advanced Non–small-cell Lung Cancer

Background

Palliative systemic therapy is frequently underutilized in patients with advanced non–small-cell lung cancer (NSCLC), for many reasons. The aim of this study was to identify patient-reported factors that may predict for treatment decisions and survival in advanced NSCLC, using the Edmonton Symptom Assessment Scale (ESAS), which is a self-reported questionnaire that quantifies symptom burden by asking patients to rate the severity of 9 common symptoms.

Cost–Utility Analysis of Pembrolizumab Versus Chemotherapy as First-Line Treatment for Metastatic Non-Small Cell Lung Cancer With Different PD-L1 Expression Levels

To evaluate the cost–utility of pembrolizumab versus chemotherapy as the first-line setting for metastatic nonsmall cell lung cancer (NSCLC) from the US health care system perspective, a Markov model was developed to compare the lifetime cost and effectiveness of pembrolizumab versus chemotherapy for untreated metastatic NSCLC, based on the clinical data derived from phase III randomized controlled trial (KEYNOTE- 042; ClinicalTrials.gov; NCT02220894). Weibull distribution was fitted to simulate the parametric survival functions. Drug costs were collected from official websites, and utility values were obtained from published literature. Total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were computed as primary output indicators. The impact of different PD-L1 expression levels on ICER was also evaluated. One-way and probabilistic sensitivity analyses were performed to assess the model uncertainty. Compared with chemotherapy, patients treated with pembrolizumab provided an additional 1.13, 1.01, and 0.59 QALYs in patients with PD-L1 expression levels of ≥50%, ≥20%, and ≥1%, with corresponding incremental cost of $53,784, $47,479, and $39,827, respectively. The resultant ICERs of pembrolizumab versus chemotherapy were $47,596, $47,184, and $68,061/QALY, in three expression levels of PD-L1, respectively, all of which did not exceed the WTP threshold of 180,000/QALY. Probability sensitivity analysis outcome supported that pembrolizumab exhibited evident advantage over chemotherapy to be cost-effective. One-way sensitivity analysis found that ICERs were most sensitive to utility value of pembrolizumab in progression survival state. All the adjustment of parameters did not qualitatively change the result. For treatment-naive, metastatic NSCLC patients with PD-L1+, pembrolizumab was estimated to be cost-effective compared with chemotherapy for all PD-L1 expression levels at a WTP threshold of $180,000/QALY in the context of the US health care system.     

Under usage of zoledronic acid in non-small cell lung cancer patients with metastatic bone disease--a short communication

Background and aim

The use of zoledronic acid (ZA) is now recommended for patients with NSCLC and metastatic bone disease (MBD). We thus examined the rates of ZA administration in NSCLC looking specifically at the use of this drug with systemic chemotherapy (ZCt) and comparing overall survival between patients who had ZCt from diagnosis to those who had chemotherapy (Ct) alone.

Method

In this retrospective audit, we analysed the data of 114 consecutive patients with stage IV NSCLC and MBD at presentation. Forty-three of these patients had received zoledronic acid and chemotherapy (ZCt) and 71 had received chemotherapy alone (Ct).

Results

Forty-three (37.7%, 43/114) of NSCLC patients diagnosed with MBD received ZA with their first chemotherapy (ZCt). Patients on ZCt, after adjustment for the planned prognostic factors (sites of disease, histology and PS), had better overall survival (OS), with a median of 34 weeks, compared to those who received chemotherapy alone, who had a median of 19 weeks (p = 0.03), HR = 0.60 (95%CI: 0.38-0.96). After adjusting for prognostic factors (sex, age. single versus doublet chemotherapy), ZCt patients still maintained a trend to better OS (p = 0.06) HR 0.63 (95%CI: 0.39-1.02) 34 versus 21 weeks.

Conclusions

The percentage of patients with MBD treated with ZA at first chemotherapy (37.7%) is low. The addition of ZA increased OS in NSCLC patients with MBD in this audit. More formal policies and dedicated trials on the treatment of MBD in NSCLC patients need to be put in place.     

Tumour necrosis factor-alpha and transforming growth factor-beta are significantly associated with better prognosis in non-small cell lung carcinoma: putative relation with BCL-2-mediated neovascularization

Recent in vivo and in vitro studies have demonstrated a wide spectrum of biologic activities of cytokines in the pathogenesis and progression of malignancy. Tumour necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) have emerged as two of the many host-derived mediators that seem to interfere with both antiproliferative and tumorigenic effects in malignant tumours including lung cancer. However, their association with tumour prognosis or prognostic factors has not yet been completely clarified. In this study, we assessed TNF-alpha and TGF-beta mRNA expression by RT-PCR technique in 61 NSCLC samples, demonstrating the presence of TNF-alpha and TGF-beta mRNA in 55.74% and 45.9% of cases, respectively. We also evaluated the expression of the two distinct transmembrane TNF receptors. TNFR-I and TNFR-II, with a PCR-positive signal in 70.49% and 65.57% of cases, respectively. In 49 of the 61 cases, we evaluated the prognostic impact of the two growth-inhibiting factors using the Kaplan-Meier analysis. In the univariate analysis patients without nodal metastatic involvement (P = 0.02), less advanced tumour stage (P = 0.02) or TNF-alpha and TGF-beta positive cancers (P = 0.01 and P = 0.03) showed a favourable prognosis in terms of overall survival. Since our previous studies demonstrated a significant association between NSCLC behaviour, neoangiogenesis and bcl-2 expression, we investigated the putative relation between TNF-alpha and TGF-beta on the one hand, and vascular count (as a measure of tumour angiogenesis) and bcl-2 protein expression, on the other hand. Our results showed a significant direct association between TNF-alpha and bcl-2 (P = 0.05) and an inverse association between TNF-alpha and microvessel count (P = 0.03). Moreover, as previously demonstrated, we observed a significant inverse correlation between bcl-2 protein expression and vascular count (P = 0.05), suggesting that the favourable effect of TNF-alpha on clinical outcome may be related to a bcl-2-mediated low neovascular development.