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T Le Chevalier

Publications and source records attributed to T Le Chevalier.

At least 19 recordsLinked to original sources
PubMed2006

Concomitant radio-chemotherapy based on platin compounds in patients with locally advanced non-small cell lung cancer (NSCLC): a meta-analysis of individual data from 1764 patients.

BACKGROUND: Despite several randomised trials comparing radiotherapy alone with concomitant radio-chemotherapy in patients with locally advanced non-small cell lung cancer (NSCLC), it is not clear whether the addition of chemotherapy improves survival. PATIENTS AND METHODS: This meta-analysis was based on individual patient data from published and unpublished randomised trials which compared radiotherapy alone with the same radiotherapy combined with concomitant cisplatin- or carboplatin-based chemotherapy. Trials with accrual completed after 2000 were excluded. Trials were sought in electronic databases, clinical trial registries and by additional manual searches. The primary endpoint was overall survival analysed using the log-rank test stratified by trials. RESULTS: There were twelve eligible trials that included a total of 1921 patients. The data from 3 trials were not available. Therefore, the analysis was based on 9 trials including 1764 patients. Median follow-up was 7.2 years. The hazard ratio of death among patients treated with radio-chemotherapy compared to radiotherapy alone was 0.89 (95% confidence interval, 0.81-0.98; P = 0.02) corresponding to an absolute benefit of chemotherapy of 4% at 2 years. There was some evidence of heterogeneity among trials and sensitivity analyses did not lead to consistent results. The combination of platin with etoposide seemed more effective than platin alone. CONCLUSIONS: Concomitant platin-based radio-chemotherapy may improve survival of patients with locally advanced NSCLC. However, the available data are insufficient to accurately define the size of such a potential treatment benefit and the optimal schedule of chemotherapy.

Aged↗
PubMed2006

Review of the pemetrexed and gemcitabine combination in patients with advanced-stage non-small cell lung cancer.

Pemetrexed is a new multitargeted antifolate that can be easily administered as a 10-min infusion every 3 weeks. The use of folic acid, vitamin B(12), and corticoid prophylaxis has significantly reduced pemetrexed-induced toxicity. Single-agent pemetrexed has shown antitumor activity in a wide range of solid tumors, including non-small cell lung cancer (NSCLC). Association with vinorelbine, cisplatin, carboplatin, and oxaliplatin have been tried, but the pemetrexed and gemcitabine combination, an easy to administer cisplatin-free doublet, has been documented in many phase 2 trials in the first-line treatment of advanced NSCLC. In vitro cytotoxic assays and phase I studies have defined several schedules of administration for pemetrexed and gemcitabine. The recommended dose is pemetrexed 500 mg/m(2) on day 1 or 8, and gemcitabine 1250 mg/m(2) on day 1 and 8, but it is unknown if pemetrexed should precede or follow gemcitabine and at what time interval. Published studies have failed to show significant differences in overall survival times despites response rates oscillating between 15% and 41%. The main toxicities are neutropenia, fatigue, skin rashes and elevated transaminases and seem to occur with similar rates in the many phase 2 trials. Hopes for the future are in tailored chemotherapy, since molecular markers of sensitivity are available for gemcitabine and pemetrexed, allowing to determinate in the future which patients will be most likely to benefit from the gemcitabine-pemetrexed doublet.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Differential expression of biomarkers in lung adenocarcinoma: a comparative study between smokers and never-smokers.

BACKGROUND: Non-small-cell lung cancer arising in never-smokers is usually of adenocarcinoma subtype. The oncogenic pathway of such tumors is poorly understood. To better define the biological characteristics of these tumors, we have compared the expression of a panel of epidermal growth factor receptor (EGFR)-related biomarkers in lung adenocarcinomas from smokers versus those in never-smokers. PATIENTS AND METHODS: Using immunohistochemical analysis, we retrospectively analyzed EGFR, pAKT, PTEN, Ki-67, p27 and hTERT expression in specimens from 190 patients with completely resected lung adenocarcinomas (43 never-smokers and 147 smokers). These analyses were performed on tissue microarrays. RESULTS: EGFR expression was higher in tumors from smokers (P < 0.01), while pAKT was overexpressed mainly in tumors from never-smokers (P = 0.01). As expected, the tumors from smokers presented a higher expression of Ki-67 and a more frequent loss of expression of p27 (P < 0.01). In a multivariate model, two biological factors (p27 and Ki-67) and two clinical factors (age and sex) showed independent significant correlation with never-smoking status. CONCLUSIONS: Lung adenocarcinomas in never-smokers have a very distinct immunohistochemical expression profile of EGFR-related biomarkers as compared with lung adenocarcinomas in smokers. High levels of EGFR and Ki-67 are observed in smokers, while never-smokers are characterized by high levels of pAKT and p27.

Adenocarcinoma↗
PubMed2005

Molecular prognostic factors in resectable non-small cell lung cancer.

Lung cancer retains the leading position in cancer-related deaths in the western countries. Non-small cell lung cancer (NSCLC) comprises more than 80% of lung cancers, and complete surgical resection of primary tumors in early-stage disease is the only potentially curative treatment. One area of intense research on early-stage NSCLC is the identification of molecular markers to complement TNM staging to fully assess the prognosis of patients and to define innovative strategies. Numerous prognostic factors have been identified in patients with early-stage NSCLC that might enable classification of such patients into different subsets corresponding to different risks of recurrence following complete resection. Most of the markers are proteins that can be detected by immunohistochemistry assays based on the antigen-antibody reaction. The present review aims at providing a panorama on classical as well as new prognostic markers. Of special interest are some molecular factors, already or currently tested from a prognostic point of view, that might also become good candidates for predicting treatment efficacy.

Biomarkers, Tumor↗
PubMed2005

Efficacy of gemcitabine plus platinum chemotherapy compared with other platinum containing regimens in advanced non-small-cell lung cancer: a meta-analysis of survival outcomes.

PURPOSE: Gemcitabine-platinum combination activity has been clearly established in a number of phase II studies. It has also been compared against other combinations in many phase III trials. It is generally believed that all such regimens have an equivalent impact on survival. This meta-analysis aims to quantify the treatment effect of gemcitabine plus a platinum agent in the treatment of advanced NSCLC and compare the combination to other regimens used globally. DESIGN: Data from a total of 4556 patients from 13 randomized trials investigating gemcitabine in combination with a platinum agent versus any other platinum-containing regimen were included in a meta-analysis of time-to-event outcomes. RESULTS: A significant reduction in overall mortality in favor of gemcitabine-platinum regimens was observed, hazard ratio (HR) 0.90 (95% CI: 0.84-0.96) with an absolute benefit at 1 year of 3.9%. Median survival was 9.0 months for the gemcitabine-platinum regimens and 8.2 months for the comparator regimens. Sub-group analysis of the first- and second-generation platinum-based comparator regimens also indicated a significant benefit for gemcitabine-platinum regimens, HR 0.84 (CI: 0.71-0.9985). Analysis of third-generation agent plus platinum regimens showed a non-significant trend favoring gemcitabine-platinum regimens, HR 0.93 (CI: 0.86-1.01). There was a significant decrease in the risk of disease progression in favor of gemcitabine-platinum regimens, HR 0.88 (CI: 0.82-0.93). An absolute benefit of 4.2% at 1 year was estimated. Median progression-free survival was 5.1 months for gemcitabine-platinum regimens compared with 4.4 months for the comparator regimens. Sub-group analysis indicated a statistically significant progression-free survival benefit for patients assigned to gemcitabine-platinum treatment compared to first- and second-generation platinum regimens, HR 0.85 (CI: 0.77-0.94), and third-generation agent plus platinum regimens, HR 0.89 (CI: 0.82-0.96).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Phase I study of PKC412 (N-benzoyl-staurosporine), a novel oral protein kinase C inhibitor, combined with gemcitabine and cisplatin in patients with non-small-cell lung cancer.

BACKGROUND: PKC412 (N-benzoyl-staurosporine), an oral inhibitor of protein kinase C, is capable of cell cycle inhibition and is endowed with anti-angiogenic properties. This dose-finding phase I study was designed to establish the maximum tolerated dose (MTD) of PKC412 when combined with cisplatin-gemcitabine. PATIENTS AND METHODS: Escalating doses of PKC412 were given every day of a 4 week cycle with cisplatin 100 mg/m2 on day 2 and gemcitabine 1000 mg/m2 on days 1, 8 and 15 in patients with non-small-cell lung cancer. Dose escalation was based on a modified continuous reassessment method. RESULTS: Twenty-three patients, assigned to four cohorts receiving PKC412 at a dose ranging from 25 to 150 mg/day were evaluable. Grade 3 diarrhea occurring in 3/4 patients at cycle 1 led us to define 150 mg/day as the MTD. The MTD based on multiple cycles was redefined as 100 mg/day, since prolonged grade 2-3 nausea/vomiting leading to treatment discontinuation occurred in 3/7 patients after repeated cycles. The next lower dose tested of 50 mg/day was therefore considered as the recommended dose for phase II trials. Among 33 cycles in eight patients, toxicity consisted of grade 1-2 diarrhea (12.5%) and asthenia (50%) with only one patient experiencing grade 3 headache at this dose level. A partial response was observed in three patients. CONCLUSIONS: The results of the present study indicate that PKC412 at a dose of 50 mg/day can be safely added to cisplatin and gemcitabine in patients with advanced non-small-cell lung cancer.

Administration, Oral↗
PubMed2004

Treatment of advanced non-small-cell lung cancer patients with ECOG performance status 2: results of an European Experts Panel.

BACKGROUND: Platinum-based combination chemotherapy is currently recommended as the standard treatment for patients with advanced non-small-cell lung cancer (NSCLC), but its benefit seems limited to fit patients with a performance status (PS) of 0 or 1. For PS2 patients, there is no consensus on standard treatment. With the aims of reviewing the evidence supporting each of these therapeutic options, possibly reaching a consensus for treatment of PS2 patients affected by advanced NSCLC in clinical practice, and suggesting the priorities for clinical research in this field, an European Experts Panel took place in Avellino, Italy in April 2003. RESULTS: and conclusions On the basis of current evidence, chemotherapy treatment appears justified for patients with advanced NSCLC and PS2. Single-agent chemotherapy (gemcitabine, vinorelbine, taxanes) could be the preferred option, although carboplatin-based or low-dose cisplatin-based doublets may represent alternative options. Stronger evidence is expected from new clinical research specifically focused on PS2 patients. Single-agent chemotherapy should be the standard arm against which experimental treatments are tested in randomised trials dedicated to PS2 patients. High priority should be given to the evaluation of tolerability and efficacy of platinum-based combinations, and to the testing of new biological agents. Another research priority is the improvement of supportive care. Patients strongly need symptomatic improvement: end points such as symptom relief, clinical benefit and quality of life should have a central position in trials dedicated to PS2 NSCLC patients.

Antineoplastic Agents↗
PubMed2004

Chemokine receptor CXCR4 and early-stage non-small cell lung cancer: pattern of expression and correlation with outcome.

BACKGROUND: The expression of CXCR4 has been implicated in metastatic dissemination in different models of breast cancer and melanoma. In the present study, we evaluated CXCR4 expression in non-small-cell lung cancer (NSCLC) and the relationship between CXCR4 expression and the prognosis of stage I disease. PATIENTS AND METHODS: Using immunohistochemical analysis, we retrospectively analyzed CXCR4 expression in specimens from 61 patients with completely resected pathologically confirmed stage I NSCLC for whom clinical follow-up data were available. RESULTS: In the present study, we have shown that: CXCR4 is expressed by tumor cells in stage I NSCLC; CXCR4 is located in the nucleus and/or in the cytoplasm of tumor cells; strong nuclear staining was observed in 17 cases (29.8%); patients whose tumors had CXCR4-positive nuclear staining had a significantly longer duration of survival than patients whose tumors had no nuclear expression (P = 0.039, log-rank test). Interestingly, the 5-year metastasis rates were 23.5% and 34.1% in patients with CXCR4-positive and CXCR4-negative nuclear expression, respectively (P = 0.2). CONCLUSION: Strong CXCR4-positive nuclear staining was associated with a significantly better outcome in early-stage NSCLC. The mechanisms underlying this clinically and biologically important finding need to be further explored.

Adult↗
PubMed2004

[Modalities of radiotherapy in small cell lung cancer: thoracic radiotherapy and prophylactic cerebral irradiation].

Small cell lung cancers (SCC) represent 20% of all lung cancers. After the initial control of the extension, only one third of the patients with SCC will finally have limited disease. The treatment of limited SCC currently relies on chemo-radiotherapeutic combinations that have improved overall survival and survival without metastases over the last few years. Nevertheless, even in limited forms, survival at 5 years varies from 10 to 15% and rarely exceeds 25% in the best series. The risk of relapse is high: although around 70% of patients with a limited form will have complete response, only 15 to 20% of them will exhibit prolonged survival. Indeed, most patients relapse, and the risk of cerebral dissemination for example is particularly high, reaching 50% at 2 years even in complete responders. After the results of a meta-analysis evaluating prophylactic cranial irradiation (PCI) among SCC complete responders, demonstrating 5% enhancement of survival at 3 years, PCI is part of the standard management of SCC in complete response. Despite the improvement in overall survival with the combined treatments, the mediocre results observed in terms of long-term survival warrant further clinical trials in order to define the optimal polychemotherapeutic and radiotherapeutic modalities, the best means of combining these two therapies and the place for new therapies.

Brain Neoplasms↗
PubMed2003

Combination of raltitrexed and oxaliplatin is an active regimen in malignant mesothelioma: results of a phase II study.

PURPOSE: The aim of this open-label phase II study was to evaluate the activity of raltitrexed (Tomudex; AstraZeneca, Cergy, France) and oxaliplatin combination therapy in patients with diffuse malignant pleural mesothelioma. PATIENT AND METHODSs: Fifteen pretreated and 55 chemotherapy-naive patients (median age, 60 years; World Health Organization performance status of < or = 2) were enrolled. Most patients (66%) had advanced disease. Patients received raltitrexed 3 mg/m2 followed by oxaliplatin 130 mg/m2 every 3 weeks. RESULTS: Twenty-four patients (34%) were classified as having a poor prognosis. In the overall study population, 14 patients (20%) had a partial response, and 32 patients (46%) had stable disease. The symptomatic response rates were as follows: shortness of breath, 36%; pain, 30%; activity, 23%; appetite, 21%; and asthenia, 20%. Median time to disease progression was 18 weeks (95% confidence interval [CI], 13 to 22 weeks). In chemotherapy-naive patients, median survival was 31 weeks (95% CI, 23 to 40 weeks) from the start of treatment and 49 weeks (95% CI, 40 to 52 weeks) from diagnosis of mesothelioma. In pretreated patients, median survival was 44 weeks (95% CI, 24 to 40 weeks) from the start of treatment and 226 weeks (95% CI, 63 to 292 weeks) from the diagnosis of mesothelioma. Overall 1-year survival was 26% (95% CI, 15.5% to 36.4%), survival was 22% (95% CI, 10.9% to 33.2%) in chemotherapy-naive patients and 40% (95% CI, 15.2% to 64.8%) in pretreated patients. Hematologic toxicity was mild, and there was no alopecia. The most common adverse events were asthenia, nausea/vomiting, and paraesthesia, and no treatment-related deaths were reported. CONCLUSION: The raltitrexed and oxaliplatin combination is an active outpatient regimen in malignant mesothelioma and has an acceptable tolerability profile.

Adult↗
PubMed2003

A retrospective analysis of the outcome of patients who have received two prior chemotherapy regimens including platinum and docetaxel for recurrent non-small-cell lung cancer.

With the availability of chemotherapy agents for first- and second-line treatment of advanced non-small-cell lung cancer (NSCLC), the patient population that requires subsequent chemotherapy is increasing. This retrospective analysis was performed to describe the clinical course after two standard or approved chemotherapy agents in patients with good overall performance status. Data were selected from patients with advanced NSCLC who had received third- or fourth-line chemotherapy after two prior chemotherapy regimens that included platinum and docetaxel given concurrently or sequentially. Prior regiments had failed due to discase progression within 90 days of chemotherapy, or unacceptable toxicity. Examination of over 700 patient records between January 1993 and January 2000 at one US and one European cancer centre revealed 43 patients that fulfilled the inclusion criteria. Response rates decreased with each line of treatment: first line, 20.9%; second line, 16.3%; third line, 2.3%; and fourth line, 0%. The disease control rate (response plus stable disease) also decreased dramatically from first- to fourth-line treatment, although it was higher for second-line treatment (74.4%) than for first-line treatment (62.8%). The median overall survival time from diagnosis was 16.4 months. The median overall survival time from the start of the last treatment (either third or fourth line) was 4 months. Patients with stage III disease at diagnosis had a longer overall survival from diagnosis than patients with stage IV disease (P=0.02). This review highlights the need for novel therapy approaches for patients with recurrent NSCLC who have failed second-line therapy and provides a baseline for the statistical design of such studies.

Adult↗
PubMed2003

Recombinant adenovirus shedding after intratumoral gene transfer in lung cancer patients.

We conducted two phase 1 trials of direct intratumoral injection of a recombinant E1E3-deleted adenovirus (AdR) encoding either the bacterial enzyme beta-galactosidase (Ad.RSVbetagal) or interleukin 2 (IL2, AdTG5327) into primary nonsmall-cell lung cancers of 21 patients. We report here virus shedding and the duration of virus expression in the tumor after intrabronchial injection of 10(7), 10(8) or 10(9) PFU of adenovirus. The infectious AdR and the viral DNA were detected in PBL, plasma, stool and aerodigestive samples in a dose-dependent manner, since cell cultures and PCRs were found to be positive mainly for samples from patients who received the highest AdR dose (10(9) PFU). We detected beta-galactosidase activity in the tumor biopsy samples of 66% of the patients, seemingly dose related, and only low levels of IL2 mRNA could be detected in tumor biopsy samples. E1 sequences were not detected by PCR in any of the PBL and bronchial samples collected after virus delivery, except in one patient. In this patient, E1 sequences were detected in PBL as well as in tumor biopsy samples collected at days 8, 30 and 60 and were correlated with longer beta-galactosidase expression in tumor samples. PBL tested before and after virus delivery contained both E1 sequences indicating that they did not result from replication-competent adenovirus (RCA) E1 sequences present in the inoculum. In addition, only on the day of the injection was Ad.RSVbetagal also detected in E1-positive PBL, indicating that virus replication in blood was very unlikely.

Adenoviridae↗
PubMed2002

Use of chemo-radiotherapy in locally advanced non-small cell lung cancer.

Lung cancer is the leading cause of cancer mortality in the Western countries for both men and women. Approximately 40% of patients present with locally advanced and/or unresectable disease. While small improvements in outcome have occurred for this group of patients in the last decade, 5-year survival remains low, ranging from 5 to 20%. Distant metastases and loco-regional progression remain significant patterns of failure. Up to the late 1980s, the standard management for locally advanced non-small cell lung cancer (NSCLC) was conventional thoracic radiotherapy, but when treated with radiotherapy alone, less than 10% of patients survived for 5 years or more. 60-70% failed at distant sites and less than 20% achieved durable local control. The addition of chemotherapy reduces the rate of distant failure, improves survival and the combination of chemotherapy and radiotherapy has become the standard of care of patients with locally advanced NSCLC. Current developments aim to optimise individual components of combined modality schedules, increase their synergism and minimise toxicity.

Antineoplastic Combined Chemotherapy Protocols↗