Survival in untreated early stage non-small cell lung cancer

BACKGROUND: The aim of this study was to determine the survival of untreated stage I and II in non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: A retrospective analysis of medical charts of all patients diagnosed with early stage NSCLC, between January 1990 and December 2001, was conducted and patients who were not treated were identified. Data on patient's age, gender, stage of the disease, pathology, reason for non-treatment and cause of death were reviewed. RESULTS: Thirty-nine patients with untreated stage I and II NSCLC were identified. The median age at diagnosis was 77 years; 66.7% were men and 33.3% were women. All patients were Caucasian and 66.7% had stage I disease, 46.2% had squamous cell carcinoma, while adenocarcinoma was found in 28.2%. The major reason for non treatment was chronic obstructive pulmonary disease (64.1%) and the main cause of death was metastatic disease (48.7%). The overall mean survival was 11.9 months. The mean survival at stage I was not statistically different from the mean survival at stage II (13.7 months vs. 8.4 months) (p < 0.12). CONCLUSION: Patients with untreated early stages NSCLC have a very poor prognosis. Alternative therapies that are better tolerated should be investigated in these patients with early stage NSCLC who cannot be offered standard treatment.     

Carboplatin and vinorelbine in untreated locally advanced and metastatic non-small cell lung cancer

The aim of this study was to assess the activity and toxicity of carboplatin/vinorelbine combination chemotherapy in unresectable locally advanced and metastatic non-small cell lung cancer. Between April 1997 and June 1999 30 patients (22 M, eight F, median age 62) received treatment with carboplatin AUC 6 on day 1, and vinorelbine 25mg/m(2) on days 1, 8 and 15. Treatment was given every 28 days for six cycles unless progressive disease occurred. Twenty-three patients (77%) had stage IV disease, and seven (23%) stage IIIB. Ninety-three percent were WHO performance status 0-1. Twenty-three patients were fully assessable. Nine patients achieved partial responses (9/23, 39%) for an overall objective response rate of 9/30 (30%; 95% CI 15-49%). The median duration of response was 2.75 months (range 1-13 months). The median progression-free survival was 2 months and the median survival 5.25 months. The actuarial 1-year survival was 20%. The median number of cycles completed was two (range 1-6). Day 15 vinorelbine was administered in only 18% of cycles. The main toxicity was myelosuppression. WHO grade III/IV neutropenia was experienced in 50% of patients, however, there were only three episodes of febrile neutropenia. Eight patients required blood transfusion and one developed grade III thrombocytopenia. Treatment was ceased in one patient because of grade IV autonomic neuropathy. No patient had significant nausea and vomiting. There were no treatment-related deaths. These results indicate that carboplatin/vinorelbine is well tolerated and has similar activity to cisplatin/vinorelbine in patients with unresectable non-small cell lung cancer, however, the median survival was considerably shorter.     

Erlotinib in non-small cell lung cancer

Erlotinib and gefitinib are quinazoline derivatives that selectively and reversibly inhibit the tyrosine kinase activity of the EGFR. Activating mutations in the EGFR confer hypersensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in patients with advanced non-small-cell lung cancer. Erlotinib has been developed in EGFR mutation-positive patients as a firstline treatment, and results from recently completed phase III studies have shown superior progression-free survival and response rates for erlotinib, compared to chemotherapy.     

BRAF-mutations in non-small cell lung cancer

Objectives

Targeted therapies in non-small cell lung cancer (NSCLC) now also include inhibitors against mutated BRAF. We present clinicopathological characteristics of nearly one thousand unselected NSCLC patients tested for the targetable V600E/K BRAF-mutation.

Material and methods

NSCLC routinely tested for EGFR-mutations at Oslo University Hospital in the period February 2011–July 2013 were tested for V600E/K BRAF-mutations using a PCR-based method.

Results

We found a BRAF-mutation frequency of 1.7% in the total cohort of 979 patients, and 2.3% among 646 adenocarcinomas. One of the BRAF-positive samples was also KRAS-mutated, and one had an ALK-translocation. None of 231 squamous cell carcinomas were BRAF-mutated. The proportion of never-smokers among BRAF-positives was high (29%).

Conclusion

BRAF-mutation analysis should be part of the subtyping of non-squamous NSCLC.     

Ifosfamide in non-small cell lung cancer

In recent years the role of chemotherapy in advanced non-small cell lung cancer (NSCLC) has been well established. Ifosfamide is an old drug still considered an effective cytostatic agent in the treatment of NSCLC. As a single agent, it has showed a response rate of 20-25%. These results are improved when it is used in combination with cisplatin and mitomycin C. Moreover, in recent years, several new drugs like gemcitabine, taxanes and vinorelbine have been identified, and combinations of two or three drugs have been tested in patients with advanced NSCLC. This paper reviews the main studies recently conducted for the treatment of NSCLC, considering the results obtained by ifosfamide alone and in combination. Three-drug regimens including first-generation cytostatic agents achieve a response rate of about 40% and median survival of 10 months. In combinations with new drugs, ifosfamide shows an improvement in response rate (50%) with a median survival of more than 1 year. Open questions in the treatment of NSCLC are whether three-drug are better than two-drug combinations, and whether cisplatin is still required.     

Advanced non-small cell lung cancer

Opinion statement The treatment of advanced non-small cell lung cancer requires histologic proof of diagnosis, careful staging, and assessment of each patient’s performance status and comorbidities. For patients with stage IIIB (pleural effusion) and stage IV disease who have a Cancer and Leukemia Group B performance status (PS) of 0 to 1, appropriate management consists of combination chemotherapy with a platinum (either cisplatin or carboplatin) combined with paclitaxel, gemcitabine, vinorelbine, docetaxel, or CPT-11. Dosages and schedules previously established by large phase II or phase III studies should be followed. Variations in the toxicity patterns, schedules of administra-tion, and economic considerations should guide the selection of the specific regimen. For patients who maintain a good performance status after first-line chemotherapy, second-line treatment may be considered. Current evidence supports the use of docetaxel as second-line treatment if the patient has not previously received this drug. Gemcitabine and paclitaxel may also have activity in this setting. Vinorelbine, ifosfamide, and CPT-11 appear to be inactive as second-line therapy for patients who have previously received platinum-based chemotherapy. For patients with a PS of 2, single-agent chemotherapy with vinorelbine, gemcitabine, or a combination of the two should be considered. Patients with poor performance status should be treated with supportive measures designed to relieve pain and acute complications because any tumor-directed therapy has limited benefit. Special situations exist in which curative therapy for metastatic disease is a possibility. Patients who present with solitary sites of metastatic disease, particularly after a long disease-free interval and in the CNS may undergo definitive surgery or radiotherapy with curative intent. Some have also reported favorable outcomes for patients with solitary adrenal or bone metastases as well. Surgical treatment or definitive radiotherapy should not be employed unless a thorough restaging evaluation is performed that includes computed tomography scan of the chest and abdomen through adrenals, brain magnetic resonance imaging, and positron emission tomography scan. A plethora of new agents targeting angiogenesis, tumor invasiveness, the hypoxic environment of tumors, and the cell cycle are currently in development.     

非小细胞肺癌的化学耐药

肿瘤的生物学特征影响化疗的疗效，由于肿瘤的化学耐药，非小细胞肺癌化疗的效力己达最大，但其预后暗淡及生存期有限。本文介绍非小细胞肺癌化疗中常用的药物，卡铂和顺铂及长春瑞宾、紫杉烷类、依立替康、吉西他滨等五组细胞毒性药物的特异性耐药机制。     

Cellular immune profile in patients with non-small cell lung cancer after weekly paclitaxel therapy

Paclitaxel is a new agent for advanced non-small cell lung cancer (NSCLC). Weekly doses may enhance antitumor activity while minimizing toxicity, but little is known about immune recovery. Paclitaxel (80 mg/m2) was administered to 10 patients with NSCLC, weekly during 3-week cycles. Natural killer (NK) activity, CD3-CD16+CD56+ NK cells, and differential counts were monitored. NK activity appeared in all patients after treatment with paclitaxel therapy NK activity showed a 27 +/- 9% decrease (mean +/- SE) on protocol day 8 and a 37 +/- 7% decrease on day 15 (p < 0.05) recovering to 89 +/- 5% of baseline on day 29. With weekly paclitaxel, a decrease in NK cell function persisted through the first cycle but then recovered. Weekly paclitaxel may be less immunosuppressive than agents such as cisplatin.     

Targeted therapy in non-small cell lung cancer

Cytotoxic chemotherapy for advanced non-small cell lung cancer (NSCLC) offers only modest benefits over best supportive care alone by modestly prolonging survival, reducing symptoms, and improving quality of life. Despite the introduction of a number of new agents over the past decade, we have seen no convincing improvements in efficacy and safety with platinum-based regimens. It appears that a plateau has been reached in the development of traditional cytotoxic chemotherapy and a new paradigm is needed. Novel treatment modalities have emerged from advances in the understanding of tumor cell biology. These sophisticated new agents home in on and neutralize specific targets in the biologic pathway of cancer. This "targeted therapy" represents a new generation of anticancer treatment and a chance to revitalize the moribund state of NSCLC treatment.     

Prognostic factors in non-small cell lung cancer

Identification of prognostic factors is critical in optimizing treatment for patients with cancer. The purpose of this work is to review the modern literature with regard to prognostic factors for patients with non-small-cell lung cancer (NSCLC) taking into account ongoing advances in clinical evaluation, staging, surgery, radiation therapy, chemotherapy, and molecular biology in this widely heterogeneous patient population.     

Sequential chemo-radiotherapy in non-small cell lung cancer

Locally advanced non-small cell lung cancer (NSCLC) stage IIIA/IIIB represents approximately 30% of NSCLC and still has a poor prognosis. In this article we give a short review on several randomized phase III trials that showed a slight but significant survival benefit for sequential chemo-radiotherapy in the treatment of locally advanced NSCLC.     

Gender-related disparities in non-small cell lung cancer

Epidemiological studies clearly outline some disparities in cancer onset, progression as well as prognosis and therapeutic response between sexes. In particular, in lung cancer, the leading cause of cancer death, at least in Western countries, a gender disparity appears now to emerge, especially for non-small cell lung cancer (NSCLC). Such a disparity is apparently due to a variety of mechanisms, ranging from genetic and epigenetic differences to gender-specific lifestyle as well as to behavioral causes and, clearly, to sex hormones activity. Here we briefly recapitulate gender differences in terms of risk factors, histopathological features and pathogenetic mechanisms in NSCLC, and hypothesize that a gender-oriented pharmacology could beneficially impact on innovative therapeutic strategies.     

Multi-targeted therapies in non-small cell lung cancer

Current treatment modalities provide limited improvement in the natural course of lung cancer, and prognosis remains poor. Lung cancer is a malignancy with great molecular heterogeneity. The complexity of the signaling process leading to cancer cell proliferation and to the neoplastic phenotype supports the necessity of interfering at different stages to avoid cancer cell resistance to therapy. For this reason, new strategies for the simultaneous inhibition of multiple molecular targets are being pursued.     

Targeted therapy in non-small cell lung cancer

Recent progress in molecular biology has enabled us to better understand the molecular mechanism underlying pathogenesis of human malignancy including lung cancer. Sequencing of human genome has identified many oncogenes and tumor suppressor genes, giving us a better understanding of the molecular events leading to the formation, progression, metastasis, and the development of drug resistance in human     

Adjuvant chemotherapy in non-small cell lung cancer

Lung cancer is the leading cause of cancer death in France. Nearly 80% of lung tumors are non-small cell lung cancers (NSCLC). Surgery is the best curative approach, but it only concerns 30% of NSCLC, since the diagnosis is frequently made in patients with locally advanced or metastatic disease. Even when surgery is performed relapse occurs in up to 50% of patients. Several adjuvant trials have been led in the late 90's after an individual data-based meta-analysis suggested a 5% survival benefit at 5 years. Among those, the IALT study, with 1 867 patients included, confirms the benefit of post-operative chemotherapy in resected NSCLC. In this article, the current status of adjuvant chemotherapy is reviewed, and future prospects are discussed.     

Microsatellite alterations in non-small cell lung cancer

Genetic alterations at 12 dinucleotide repeat loci located on human chromosomes 2, 3, 12, and 17 have been analyzed in non-small cell lung cancer from Thai patients. Seventeen out of 30 cases (57%) harbored the microsatellite alterations. Of the 30 cases, 19 patients had a history of tobacco smoking, of whom 14 (74%) were in the group with microsatellite alterations, whereas 3 out of 11 non-smokers (26%) had these alterations. The frequency of microsatellite alterations among smokers was significantly higher than it was in non-smokers (P = 0.01 Fisher's exact test; odds ratio; 7.47).     

非小细胞肺癌辅助化疗研究进展

近年来,非小细胞肺癌(NSCLC)术后辅助化疗的Ⅲ期随机临床试验结果已陆续报道,术后辅助化疗逐渐被接受,已成为Ⅱ～ⅢA期非小细胞肺癌综合治疗的重要措施之一.本文就NSCLCⅢ期随机临床试验结果作一综述.