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PubMedDate not supplied

[Granulocyte colony stimulating factor (G-CSF) in diagnosis and monitoring of non-small-cell lung cancer (NSCLC)].

Granulocyte-colony stimulating factor (G-CSF) is one of the glycoproteins called colony-stimulating factors (CSFs). It has been shown that the target of the actions of CSFs are not limited to hematopoietic cells but can also affect the proliferation of nonhematopoietic cells. Some clinical investigations have shown the presence of cell surface receptors for G-CSF in lung cancer cells and autologous production of G-CSF in various human cell lines derived from non-small-cell lung cancer (NSCLC). The purpose of this investigation was to compare serum levels of G-CSF in NSCLC patients to a control group, to assess pre- and post treatment levels of G-CSF in relation to levels of commonly accepted tumour markers such as carcinoembryonic antigen (CEA) and cytokeratin fragment 19 (CYFRA 21-1), and to define the sensitivity of G-CSF in NSCLC. In this study, the serum levels of tumour markers were measured in 34 patients with NSCLC and in 20 healthy subjects. Serum samples were drawn before surgery and 10, 30, 90, 180 and 270 days after surgery. G-CSF and CEA were assayed using ELISA system and CYFRA 21-1 was measured by radioimmunoassay (RIA). Preoperative level of G-CSF was significantly increased in cancer patients relative to the control group. Concentrations of G-CSF and CYFRA 21-1 were decreased on the 10th day, but CEA on the 30th day after operation. The diagnostic sensitivity of G-CSF was 66%, CEA--62% and CYFRA 21-1--51%. Combined use of two markers increased the sensitivity in comparison to the use of G-CSF only. These results suggest that G-CSF may be useful in diagnostic and monitoring of NSCLC, but they need further studies.

Adult↗

PubMed2001

[Detection of neuroendocrine differentiation in NSCLC and its clinical significance].

OBJECTIVE: To study differentiation of neuroendocrine (NE) in non-small cell lung carcinoma (NSCLC) and its effect on the responsiveness to chemotherapy. METHODS: Neuron-specific enolase (NSE), chromogranin A (CgA) and synaptophysin (SYN) were detected in 42 cases of NSCLC by using Western blot and immunohistochemistry. Electron microscopy was also used to observe the ultrastructure of NE granule in above specimens. The relationship between the chemotherapeutic responsiveness and the differentiation of NE in carcinoma tissues was evaluated. RESULTS: (1) The positive rate of NE detected by Western blot is higher than that detected by immunohistochemistry and electron microscopy. (2) There is no relationship between the expression of NE and the type of lung carcinoma as well as the differentiated degree of carcinoma. (3) The positive rate of three markers detected by immunohistochemistry and Western blot methods in the group of responsive to chemotherapy is higher than that in non-responsive group (P < 0.05). CONCLUSIONS: There is a high rate of NE differentiation in NSCLC, of which NSE's rate is highest, SYN takes second place, and CgA's rate is lowest. Immunohistochemistry and Western blot method are both very useful for the diagnosis of NE differentiation in NSCLC. The sensitivity of Western blot is higher than immunohistochemistry. The differentiation of NE may be one of the factors effected the chemotherapy in NSCLC.

Aged↗

PubMed2000

[Telomerase activity in human non-small cell lung cancer (NSCLC)].

OBJECTIVE: To investigate the activity of telomerase in human non-small cell lung cancer (NSCLC) and the correlation of telomerase activity with the cancer development. METHODS: Totally 48 cases of NSCLC tissues were studied accompanied with 7 cases of normal lung tissues and 12 samples of lung tissues adjacent to the tumor. The telomerase activity was detected using Telomerase PCR ELISA kit. Statistics study included chi(2)-test and the exact probabilities. The significance level chosen was P value less than 0.05 (P < 0.05), and all tests were two-sided. RESULTS: 75% (36/48) of NSCLC tissues possessed the expression of telomerase activity and only 8.33% (1/12) of tissues adjacent to tumor and none of the normal lung tissue enabled to express telomerase activity. The statistical difference was significant (P < 0.05). No significant difference was found between different histological types of NSCLC, however, the frequency of telomerase expression differed significantly between tumors of well/mordeately differentiated and poorly differentiated; stage I and stage II/III. CONCLUSION: Telomerase activity might be a good marker in estimating the occurrence, development and diagnosis of NSCLC.

Adenocarcinoma↗

PubMedDate not supplied

Cut-off levels of NSE to differentiate SCLC from NSCLC.

Neuron-specific enolase (NSE) is a specific tumor marker in small cell lung cancer (SCLC) patients, however, it has been reported that serum NSE levels are elevated in some patients with non-small cell lung cancer (NSCLC). To determine the most suitable cut-off level to distinguish between these two types of cancers, NSE levels were measured on serum samples of 417 patients with lung cancer without clinical information. Receiver operating characteristic (ROC) curve showed 14.5 ng/ml as a cut-off level and the 95 percentile serum NSE level in NSCLC was 20.5 ng/ml. None of the NSCLC patients had serum NSE levels more than 70 ng/ml. The measurement of serum NSE provides a discrimination between NSCLC and SCLC. If an NSCLC patient presents with a NSE level >20.5 ng/ml, pathological features must be examined with regard to the neuroendocrine differentiation.

Adult↗

PubMed2003

[Prognostic value of symptoms in patients treated surgically for non-small cell lung cancer (NSCLC)].

UNLABELLED: The aim of this study was to remind, that the presence of symptoms in patients qualified to surgical treatment for NSCLC can be considered as an unfavorable prognostic factor. MATERIAL AND METHOD: The study group consisted of 231 patients discharged from the Clinic between 1988 and 1991 after surgical treatment for NSCLC. Information about complaints and symptoms were based on archival records. NSCLC stages have been defined from the analysis of operation records. RESULTS: Among 231 patients treated surgically for NSCLC 189 (81.9%) had complaints during last 4-96, av. 24 weeks. 106 (45.9%) patients complained of cough, and 68 (29.4%) of chest pain and bloody sputum. Of 189 patients with complaints at admission to the Clinic, 31.7% survived 5 years, and 25.4% survived 10 years after surgical treatment. In the group of 42 patients with lung cancer detected accidentally, 71.4% survived 5 years, and 57.3% survived 10 years (p<0.001) CONCLUSIONS: 1. The presence of symptoms at patients operated for NSCLC is an unfavorable prognostic factor. 2. Chest pain and a rapid loss of body mass are particularly bad prognostic factors.

Adult↗

PubMed2005

Deletions at chromosome 2q and 12p are early and frequent molecular alterations in bronchial epithelium and NSCLC of long-term smokers.

Most lung cancer is attributed to long-term smoking. In order to define chromosomal regions with an accumulation of smoking-related early molecular damage, we applied 15 microsatellite markers at 8 chromosomal regions (2q35-q36, 3p21.3, 3p14.2, 3p25, 10q11.2, 11p14-15, 12p13.1-p12.3 and 12q14) in an allelotyping study. We studied samples of 42 patients with primary non-small cell lung cancer (NSCLC) (25 squamous cell carcinomas, 13 adenocarcinomas, 2 large cell and 2 bronchioalveolar carcinomas) to compare the frequency of allelic loss in cancer tissue of smokers with matched bronchial epithelium. As a control group we used 11 samples of non-smokers. In NSCLC we found significantly higher frequencies of loss of heterozygosity (LOH) than in matched tumor free bronchial epithelium (p = 0.007). Most frequently, allelic loss was detected in NSCLC at chromosome 3p [3p25 (46%), 3p21.3 (45%), 3p14 (40%)], at 2q35 (24%), 12p12 (29%) and 12q14 (13%), but infrequently at 10q11 (7%) and 11p14-15 (5%). In corresponding histological normal bronchial epithelium, the highest percentage of LOH was found at chromosome 3p [3p21 (17%), 3p25 (12%), 3p14 (9%)] and chromosome 2q (2q35-q36) (17%) and 12p (12p12-p13) (12%). LOH in histologically normal bronchial epithelium was significantly associated with long-term smoking (p = 0.048), especially at chromosome 12p12 (p = 0.018). Our results demonstrate two further deletion hot spots at the chromosomal region 2q35-q36 and 12p12-p13 in tumor tissue of NSCLC and matched histological normal bronchial epithelium of long-term smokers, reflecting a phenomenon referred to as 'field cancerization'. These chromosomal regions represent interesting loci for potential NSCLC associated tumor suppressor genes and could be useful as screening markers for molecular risk assessment of smokers.

Adult↗

PubMed1998

Serum tumor marker CYFRA 21-1 in the diagnostics of NSCLC lung cancer.

Cytokeratins are epithelial markers whose expression is not lost during malignant transformation. The level of soluble cytokeratin fragment 19 was measured with an enzyme immunoassay method developed by Boehringer Mannheim (Enzymum-test CYFRA 21-1) in the serum of 200 male and 50 female patients with NSCLC (Non Small Cell Lung Cancer) lung cancer (120 planocellulare and 80 adenocarcinoma in males; 22 planocellulare and 28 adenocarcinoma in females). The comparative group comprised 50 young healthy males and 50 females without any clinical proof for malignancy or any other lung disease. The aim of this investigation was to find out if any possible statistical difference exists in the serum level of CYFRA 21-1 between patients with lung cancer and healthy controls, and also between different types of lung cancers. The mean value of serum CYFRA 21-1 in NSCLC (6.25 ng/ml) was significantly higher than in healthy controls (1.26 ng/ml) (p < 0.001). Sensitivity for CYFRA 21-1 (using 3.3 ng/ml, a cut-off value corresponding to a 98% specificity for healthy controls) in NSCLC was 60.5%. Positive CYFRA 21-1 levels were significantly higher in patient with carcinoma planocellulare (66.2%) than in adenocarcinoma (52.1%). CYFRA 21-1 levels were significantly different between squamous cell carcinoma (6.52 ng/ml) and adenocarcinoma (5.86 ng/ml) (p < 0.05). Our results indicate that CYFRA 21-1 may be a useful tumor marker in NSCLC, especially in carcinoma planocellulare. CYFRA 21-1 may also be useful in identification of the preoperative stages of diseases and the postoperative monitoring of NSCLC.

Adenocarcinoma↗

PubMed2026

DESTINY-Lung06: trastuzumab deruxtecan and pembrolizumab as first-line treatment for HER2-overexpressing, PD-L1 TPS <50% NSCLC.

Non-small cell lung cancer (NSCLC) that overexpresses human epidermal growth factor receptor 2 (HER2) is associated with poor prognosis, and no HER2-targeting therapies for HER2-overexpressing NSCLC are currently approved in the first-line setting. Pembrolizumab plus pemetrexed and platinum-based chemotherapy is a recommended first-line treatment option for nonsquamous NSCLC with no actionable genomic alterations. However, improved outcomes with pembrolizumab-based therapies correlate with higher programmed death-ligand 1 (PD-L1) levels, underscoring the need for more targeted treatment options for patients with lower PD-L1 tumor proportion scores (TPS; <50%). DESTINY-Lung06 is a multicenter, open-label, randomized, phase III trial evaluating the efficacy and safety of trastuzumab deruxtecan (T-DXd) in combination with pembrolizumab in the first-line setting in patients with HER2-overexpressing (≥25% moderate/strong membrane staining), PD-L1 TPS <50% NSCLC. Planned enrollment will be approximately 686 patients randomly assigned to either T-DXd 5.4 mg/kg with pembrolizumab 200 mg intravenously every 3 weeks (Q3W) or pembrolizumab 200 mg plus pemetrexed 500 mg/m2 with platinum-based chemotherapy (cisplatin 75 mg/m2 or carboplatin under the concentration-time curve 5 mg min/mL) intravenously Q3W. Progression-free survival by blinded independent central review and overall survival are the primary and key secondary endpoints of the study, respectively.Clinical trial registration: www.ClinicalTrials.gov identifier is NCT06899126; EudraCT identifier is 2024-515658-26-00.

First-line↗

PubMed2006

A phase II study of irinotecan plus cisplatin for patients with advanced stage IIIB or IV NSCLC previously treated with nonplatinum-based chemotherapy.

BACKGROUND: Irinotecan (1) and cisplatin (P) are active chemotherapy agents with clinical synergy in non-small-cell lung cancer (NSCLC). We evaluated the efficacy of IP regimen as a salvage treatment of patients with NSCLC that progressed after nonplatinum-containing regimen(s). METHODS: Eligibility required histologically confirmed NSCLC, bidimensionally measurable disease, ECOG PS 0-2, and progressive disease after nonplatinum-based chemotherapy. Treatment consisted of I (65 mg/m2) and P (30 mg/m2) i.v. on Days 1 and 8 of a 21-day cycle, for a maximum of 6 cycles. An informed consent was obtained from all patients. RESULTS: Between August 2002 and May 2004, 32 patients with median age of 56 years (range, 42-74) were enrolled. Twenty-four (75%) patients were men, and 28 (88%) had ECOG PS 0 or 1. Twenty-five patients had adenocarcinoma and 6 had squamous-cell carcinoma. All patients were evaluated for response and toxicity, and the response rate was 40.6%. After a median follow-up of 18.5 months, the median survival time was found to be 9.3 months, with a 1-year survival rate of 43.8%. Toxicities were moderate and manageable, with 47% G3 and 9% G4 neutropenia, 19% G3 diarrhea, and 22% G3 asthenia. There was no G4 nonhematologic toxicity. CONCLUSIONS: The irinotecan and cisplatin combination is an active and well-tolerated regimen for the patients with advanced NSCLC that progressed after nonplatinum-containing regimen(s).

Adenocarcinoma↗

PubMed2004

Rescue of death receptor and mitochondrial apoptosis signaling in resistant human NSCLC in vivo.

Non small cell lung carcinoma (NSCLC) is a highly lethal malignancy that often becomes resistant to chemotherapy. To determine whether alterations in apoptotic signaling might contribute to such resistance, we established in vitro and in vivo models for sensitive and resistant human NSCLC. We found that resistance is due to multiple defects found in expression of CD95-L, CD95 and members of the Bcl-2 and IAP family, as well as caspase-8, -9 and -3 as examined by immunohistochemistry, Western blot analysis, gene array analysis and functional assays. Failure to activate death receptor, as well as mitochondrial apoptosis signaling, points to a central role of caspases. To restore apoptosis signaling we transfected NSCLC xenografts on nude mice with caspase-8 and -9. This treatment strongly induced apoptosis per se and sensitized the tumors to cisplatin-induced cell death. Thus, these findings indicate that re-expression of caspases might be an effective strategy to restore sensitivity for chemotherapy in NSCLC in vivo.

Animals↗

PubMed2001

A modified mutagenic PCR-RFLP method for K-ras codon 12 and 13 mutations detection in NSCLC patients.

Evidence from many investigators has shown that mutations in the first exon of K- ras gene occur at elevated frequencies in lung, pancreatic and colon carcinoma and seem to be of prognostic importance. The aim of this study was to develop an effective method for the detection of K- ras mutations in codons 12 and 13 in non-small-cell lung cancer (NSCLC) patients in order to investigate correlation with clinical outcome. DNA was extracted from tumour and neighbouring non-neoplastic lung tissues from 70 patients and screened for codon 12 and 13 mutations. We applied a mutagenic PCR-restriction fragment length polymorphism for both codon 12 and 13 mutation detection. Codon 12 mutation was identified in 20% of NSCLC patients, whereas no codon 13 mutation was detected. As expected, the respective non-neoplastic tissues exhibited no mutations. We observed an increased codon 12 mutation prevalence in adenocarcinoma comparing to other types of carcinomas. Follow-up for 29 patients with a mean time of 12 months indicates an increased relapse rate in NSCLC patients with the K- ras codon 12 mutation. Furthermore, a trend towards increased percentage of mutant samples was observed in the advanced stage group of patients. We provide evidence that our approach is a fast and reliable method for screening K- ras exon 1 mutations in tumour samples from NSCLC patients.

Carcinoma, Non-Small-Cell Lung↗

PubMed1990

A randomized trial fo three cisplatin-containing regimens in advanced non-small-cell lung cancer (NSCLC): a study of the Umbrian Lung Cancer Group.

Survival in patients with locally advanced (stage III Mo) and metastatic (Ml) non-small-cell lung cancer (NSCLC) is short. Phase II studies have reported objective responses ranging from 20% to 60% using cisplatin-based chemotherapeutic regimens, yet few have shown improvement in median survival. In our phase II pilot studies with cisplatin (CDDP) and etoposide (VP-16), we observed a 26% response rate; with CDDP, VP-16, and mitomycin-C, a 38% response rate was obtained in advanced NSCLC patients. A total of 156 consecutive patients with locally advanced and metastatic NSCLC were randomized to one of three treatment arms to determine whether the chemotherapy protocols had any effect on response rate and median survival in a large, randomized study. Arm 1 consisted of CDDP (120 mg/m2 x 3 weeks); arm 2, of CDDP (120 mg/m2) and VP-16 (100 mg/m2 given i.v. on days 1-3), repeated every 3 weeks; and arm 3, of CDDP (120 mg/m2) and VP-16 (100 mg/m2 on days 1-3) given every 3 weeks, plus mitomycin C (10 mg/m2 on days 1, 21, and 42, then every 6 weeks, for a maximal dose of 100 mg). After 71 patients had been enrolled in the study, we stopped accrual in the CDDP arm due to a lack of response [1 complete response (CR) in 24 patients; 4%] and continued enrollment in the two combination-chemotherapy arms. In the CDDP/VP-16 arm a 30% response rate [1 CR, 18 partial responses (PRs)] was obtained, and in the CDDP/VP-16 mitomycin C arm a 26% response rate (4 CRs, 11 PRs) was seen among a total of 150 evaluable patients. Responses were observed in 31% of patients with favorable performance status (PS) (ECOG 0-1) vs 14% in patients with a poor PS (ECOG 2-3). Of patients with locally advanced disease (III Mo), 17 (33%) obtained an objective response, compared with 20 patients (20%) with metastatic disease. Median survival was 18 weeks in the CDDP arm, 35 weeks in the CDDP/VP-16 arm, and 37 weeks in the CDDP/VP-16/mitomycin C arm. The median survival in the multimodal chemotherapy arms was significantly greater than that obtained with CDDP alone. Toxicity was predominantly myelosuppression in the mitomycin C-containing arm (27%, wtto grade 3-4). Our study shows that combination chemotherapy using CDDP/VP-16 is active and safe in the treatment of advanced NSCLC patients with a good performance status. The addition of mitomycin C did not improve the therapeutic response.

Adult↗

PubMed1998

[Docetaxel (taxotere): current status of clinical development in non-small-cell bronchial carcinoma (NSCLC)].

BACKGROUND: Docetaxel (Taxotere) as a "stabilizing antitubulin" has in the last few years gained the reputation of being one of the most effective cytotoxic drugs in the therapy of NSCLC. Up until now it has primarily been used in clinical studies for both single agent- and combination chemotherapy being tested in a variety of different treatment regimens not only for advanced disease but also for early stage NSCLC. RESULTS OF STUDIES: Clinical investigations of Docetaxel in NSCLC continue and currently focus upon randomized studies, new combination chemotherapy regimens, its simultaneous use in combination with radiotherapy as well as trials within multi-modality treatment concepts. The preliminary results of these studies underline the importance of Docetaxel for NSCLC and confirm the positive results stemming from previous single agent- and combination therapy investigations.

Antineoplastic Agents, Phytogenic↗

PubMed2004

Oral vinorelbine given as monotherapy to advanced, elderly NSCLC patients: a multicentre phase II trial.

Vinorelbine intravenously (i.v.) demonstrated its efficacy and tolerability in advanced non-small cell lung cancer (NSCLC) patients, including elderly subjects. Since vinorelbine is now available as an oral formulation this phase II open study was designed to evaluate its activity and tolerability in advanced, elderly NSCLC patients. A total of 56 chemonaive patients were recruited from April 2001 through to March 2002. The dosage schedule, already tested in younger NSCLC patients, was 60 mg/m(2)once a week for three weeks (first cycle), followed by 80 mg/m(2) once a week until disease progression or development of unacceptable toxicity. A limited sampling scheme was used for performing pharmacokinetic analysis on 52 of 56 patients enrolled in the study. Treatment was well tolerated with grade 3/4 neutropenia in 11/17 patients (20/30%) and febrile neutropenia in 1 (2%). Six partial responses (11%) and 25 stable disease responses were recorded, with a disease control rate of 55%. Median overall survival was 8.2 months (95% Confidence Interval (CI) [6.2-11.3]). The clinical benefit response rate was 31% on 32 evaluable patients. Pharmacokinetic profiles appeared quite similar to the historical profiles recorded following i.v. administration. Oral vinorelbine appears to be a reasonable alternative to i.v. vinorelbine, both in terms of activity and tolerability, in advanced, elderly NSCLC patients.

Administration, Oral↗

PubMed2004

Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels, as prognostic indicators in NSCLC.

OBJECTIVES: Non-small cell lung cancer (NSCLC) tissue produces numerous growth factors, which are multifunctional and considered predictive of patient survival. This study sought to evaluate the relationship between concentrations of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) in NSCLC tissue and clinicopathological factors, and determine whether these factors correlate with long-term survival. METHODS: We retrospectively investigated 71 patients with histologically confirmed adenocarcinoma or squamous cell carcinoma of the lung, for whom the primary curative approach was surgery, and who received no chemotherapy or radiotherapy prior to surgery. bFGF, VEGF, HGF were measured in extracts prepared from these 71 frozen tissue samples by ELISA. Five- and 10-year survival was obtained to determine the most important predictors of long-term survival. RESULTS: Among clinicopathological parameters, the mean concentration of bFGF was significantly higher in tissue extracts from cases involving metastatic nodal involvement (87.5+/-69.3 ng/100 mg protein) than in those without nodal involvement (57.6+/-42.5 ng; P<0.05). Levels of VEGF in adenocarcinoma (26.8+/-34.0 ng) were higher than for squamous cell carcinoma (12.2+/-13.8 ng; P<0.05). HGF levels also demonstrated histological differences (14.7+/-7.7 vs. 10.6+/-9.7 ng, P<0.05). bFGF protein levels were basically the same, but showed no statistically significant differences with respect to histological type (72.5+/-55.2 vs. 63.6+/-51.5 ng). Patients with high levels of bFGF or VEGF showed significantly worse survival rates than patients with low levels (P=0.0059; P=0.0134). In particular, high concentrations of both bFGF and VEGF correlated with markedly poor prognosis (P<0.0001). Multivariate analysis indicated that lymph node involvement and levels of bFGF and VEGF were independent prognostic factors in cases of NSCLC (adenocarcinoma or squamous cell carcinoma) involving patients who had undergone curative resection. CONCLUSIONS: Adenocarcinoma associated with lung cancer is regarded to have biological characteristics that distinguish it from squamous cell carcinoma. Node invasion may be associated with bFGF. bFGF and VEGF augment each other and are associated with leading to poor prognosis. The results of this study suggests that effective therapy to block angiogenesis may need to address at least both of these factors in cases of NSCLC.

Aged↗

PubMed2025

A Single-Arm Phase 2 Study of Sotorasib Plus Carboplatin and Pemetrexed in Patients With Advanced Nonsquamous NSCLC With KRAS G12C Mutation (WJOG14821L, SCARLET).

INTRODUCTION: The efficacy and safety of sotorasib plus platinum doublet chemotherapy in KRAS G12C-mutated nonsquamous NSCLC (nonsq NSCLC) have been previously reported with a limited follow-up period. METHODS: SCARLET is a single-arm phase 2 study involving chemotherapy-naive patients with KRAS G12C-mutated nonsq NSCLC. The participants received 960 mg daily plus four cycles of carboplatin (area under the curve = 5)/pemetrexed 500 mg/m2, followed by sotorasib/pemetrexed until disease progression. The primary end point was the overall response rate (ORR) and the secondary end points were progression-free survival (PFS), overall survival, and safety. Using plasma samples, next-generation sequencing was performed at baseline, 3 weeks, and during disease progression (the Japan Registry of Clinical Trials number 2051210086). RESULTS: Thirty patients were enrolled between October 2021 and July 2022 with a median follow-up of 14.8 months. ORR was 88.9% (80% confidence interval [CI]: 78.5%-94.8%, 95% CI: 70.8%-97.6%), median PFS was 6.6 months (95% CI: 5.3-16.7 mo), and median overall survival was 20.6 months (95% CI: 8.1 mo-not estimated). Among patients with programmed death-ligand 1 expression levels of 1% or higher and less than 1%, the ORRs were 82.3 and 100%, respectively, and the median PFS was 7.6 and 9.7 months, respectively. Using plasma samples, patients without KRAS G12C at baseline, without KRAS-related pathway co-alterations, or who cleared KRAS G12C at 3 weeks had better median PFS (16.7, 13.9, 8.7 mo, respectively). Tumor protein 53 mutations and EGFR and MET amplification were detected as acquired resistance. CONCLUSIONS: In patients with KRAS G12C-mutated nonsq NSCLC, sotorasib plus carboplatin/pemetrexed reported favorable efficacy, particularly for patients with less than 1% programmed death-ligand 1, with manageable toxicity.

Humans↗

PubMed2004

MDM2 gene amplification: a new independent factor of adverse prognosis in non-small cell lung cancer (NSCLC).

The prognostic impact of MDM2 amplification in non-small cell lung cancer (NSCLC) remains unknown. In this study, we investigated the occurrence of MDM2 amplification in surgically treated NSCLC patients. Molecular data were correlated with clinicopathological factors and evaluated for their prognostic value. The study group included 116 NSCLC patients who underwent pulmonary resection between 1996 and 1999. MDM2 amplification was assessed by real-time PCR using hybridization probe format on a LightCycler (Roche). The calculated ratio was a MDM2 value normalized to the amplification of the housekeeping gene phenylalaninhydroxylase (PAH). Survival curves were drawn according to the Kaplan-Meier method and compared with the use of the log-rank test. Multivariate analysis was based on Cox regression analysis. MDM2 amplification was found in 24 patients (21%). There was no relationship between MDM2 amplification and clinicopathological factors, such as sex, age and stage of disease, pT, pN, histology and tumor differentiation. Median disease-free survival (DFS) in patients with and without MDM2 amplification was 3 and 31 months, and 5-year DFS 24 and 33%, respectively (log-rank, P = 0.02). Likewise, median overall survival (OS) in patients with and without MDM2 amplification was 9 and 33 months, respectively, and 5-year OS 24 and 39%, respectively (log-rank, P = 0.01). The strong prognostic relevance of MDM2 amplification for both DFS and OS was confirmed in multivariate analysis (P < 0.01 for both comparisons). Our results suggest that MDM2 gene amplification analysis provides additional prognostic information in surgically treated NSCLC patients.

Adenocarcinoma↗

PubMed2006

Cyclin D1 (CCND1) A870G gene polymorphism modulates smoking-induced lung cancer risk and response to platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients.

PURPOSE: The cyclin D1 (CCND1) A870G gene polymorphism is linked to the outcome in patients with resectable non-small cell lung cancer (NSCLC). Here, we investigated the impact of this polymorphism on smoking-induced cancer risk and clinical outcome in patients with NSCLC stages I-IV. METHODS: CCND1 A870G genotype was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (RFLP) of DNA extracted from blood. The study included 244 NSCLC patients and 187 healthy control subjects. RESULTS: Patient characteristics were: 70% male, 77% smokers, 43% adenocarcinoma, and 27% squamous cell carcinoma. Eighty-one percent of the patients had stages III-IV disease. Median age at diagnosis was 60 years and median survival was 13 months. Genotype frequencies of patients and controls both conformed to the Hardy Weinberg equilibrium. The GG genotype significantly correlated with a history of heavy smoking (>or=40 py, P=0.02), and patients with this genotype had a significantly higher cigarette consumption than patients with AA/AG genotypes (P=0.007). The GG genotype also significantly correlated with tumor response or stabilization after a platinum-based first-line chemotherapy (P=0.04). Survival analysis revealed no significant differences among the genotypes. CONCLUSION: Evidence was obtained that the CCND1 A870G gene polymorphism modulates smoking-induced lung cancer risk. Further studies are required to explore the underlying molecular mechanisms and to test the value of this gene polymorphism as a predictor for platinum-sensitivity in NSCLC patients.

Adult↗