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J J Lafitte

Publications and source records attributed to J J Lafitte.

At least 19 recordsLinked to original sources
PubMed2005

Survival improvement in resectable non-small cell lung cancer with (neo)adjuvant chemotherapy: results of a meta-analysis of the literature.

The recent publication of many randomised trials about (neo)adjuvant chemotherapy in resectable non-small cell lung cancer (NSCLC) has prompted our group to update a prior meta-analysis of the literature. Randomised studies published in French and English between 1965 and June 2004 were included in this analysis. A qualitative assessment of each trial was first performed using the European lung cancer working party (ELCWP) and the Chalmers' scales. In absence of statistically significant quality difference between positive and negative trials, a quantitative aggregation (meta-analysis) of the individual results was performed. Two trials for which data were available on ASCO virtual meeting website were also included in the meta-analysis. Twenty-five studies eligible for this analysis assessed chemotherapy as induction (n = 6) or adjuvant to surgery (n = 19). No quality difference was detected between positive and negative trials according to the two scores, whatever all trials were combined or only adjuvant chemotherapy studies were considered. The overall meta-analysis showed that the hazard ratio (HR) of the combined results was 0.66 (95% CI 0.48-0.93) in favour of the addition of induction chemotherapy to a standard surgical procedure and 0.84 (95% CI 0.78-0.89) in favour of adjuvant chemotherapy. The effect was significant for adjuvant chemotherapy in stages I and II with a HR of 0.88 (95% CI 0.83-0.94). It was not statistically significant in stage III although the trend was in favour of chemotherapy whatever adjuvant (HR = 0.85; 95% CI 0.69-1.04) or (neo)adjuvant (HR = 0.65; 95% CI 0.41-1.04) chemotherapy was tested. In conclusion, our meta-analysis shows the efficacy of adjuvant chemotherapy in stages I and II resected NSCLC. More data are needed to confirm such a role for induction chemotherapy. Further trials should separate stage III disease from earlier stages.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

A phase II study evaluating the cisplatin and epirubicin combination in patients with unresectable malignant pleural mesothelioma.

Few chemotherapeutic agents have demonstrated their efficacy in malignant mesothelioma. The cisplatin plus doxorubicin combination has one of the highest response rates. Epirubicin is an anthracyclin, analogous to doxorubicin, with a different toxicologic pattern. As there are no data on the activity of the combination cisplatin plus epirubicin in malignant mesothelioma, the European Lung Cancer Working Party (ELCWP) designed a phase II study with response rate as primary objective. Sixty-nine eligible patients with malignant pleural mesothelioma were centrally registered. The majority of the patients were male (n=59), had a Karnofsky performance status of 80 or more (n=62) and presented with an epithelial histologic subtype (n=43). Median age was 62 years. In nine patients, metastases were documented at the initial work-up, mainly in bone, lung and skin. Three hundred and twenty-four cycles of chemotherapy were administered. The main toxicities were nausea and vomiting, neutropenia and alopecia. Among 63 assessable patients, response rate was 19.0% (95% confidence interval [CI] 9-29%). Median survival was 13.3 months. In multivariate analysis, poor prognostic factors for survival were neutrophil count and CALGB groups 4-6. In conclusion, cisplatin plus epirubicin appears as an effective regimen in malignant mesothelioma, with a favourable toxicity profile. However, it does not demonstrate superior activity to other active regimens in this disease.

Adult↗
PubMed2004

Survival is better predicted with a new classification of stage III unresectable non-small cell lung carcinoma treated by chemotherapy and radiotherapy.

UNLABELLED: The 1997 International staging system (ISS) classification separated stage III non-small cell lung cancer (NSCLC) into stages IIIA and IIIB. In a previous study including unresectable NSCLC initially treated with chemotherapy, we analysed survival according to tumour (T) and node (N) stages and derived a classification into stages IIIbeta (T3-4N3) and IIIalpha (other TN stage III) that had a better discrimination on survival distribution. The aim of this study was to validate these results in a further set of patients. Patients with unresectable stage III NSCLC included in a phase III trial assessing the role of increased dose chemotherapy (SuperMIP: mitomycin 6 mg/m2, ifosfamide 4.5 g/m2, cisplatin 60 mg/m2, carboplatin 200 mg/m2) in comparison to standard chemotherapy MIP (mitomycin 6 mg/m2, ifosfamide 3 g/m2, cisplatin 50 mg/m2), before thoracic irradiation (60 Gy in 30 fractions over 6 weeks) were the subject of this study. Survival distributions were assessed by the method of Kaplan-Meier. Survival comparisons were made by the log-rank test. Multivariate analyses using Cox regression models, included all potential prognostic factors for survival with a P-value <0.2 in univariate analysis. According to the 1997 International staging system classification, 328 eligible patients were included in the study. There was no imbalance between the two arms. Five parameters were significantly associated (P < or = 0.05) with survival in univariate analysis: European lung cancer working party (ELCWP) staging (IIIalpha[n = 294 pts] versus IIIbeta [n = 46]), Karnofsky index, weight loss, platelet count and haemoglobin level. These variables as well as the 1997 ISS staging, white blood cell (WBC) count, LDH and sodium levels were included in a multivariate analysis. Two models were constructed, including either the ELCWP or the 1997 ISS. In model 1 (ISS included), Karnofsky index (HR 0.69; 95% confidence interval (CI) 0.47-1.00; P = 0.05) and haemoglobin (HR 1.49; 95% CI 1.11-1.99; P = 0.007) were found significant. In model 2, including ELCWP staging, two variables were associated with survival: ELCWP staging (HR 1.68; 95% CI 1.20-2.35; P = 0.002) and haemoglobin (HR 1.54; 95% CI 1.15-2.07; P = 0.01). CONCLUSION: In initially unresectable stage III NSCLC treated by chemotherapy and radiotherapy, we validated the results of our previous study. The classification into stages IIIbeta (T3-4N3M0) and IIIalpha (other TN stage III) better discriminates the patients in term of survival than the 1997 ISS classification.

Aged↗
PubMed2003

Citation indexes do not reflect methodological quality in lung cancer randomised trials.

BACKGROUND: Citation factors are applied to assess scientific work despite the fact that they were developed commercially in order to compare competing journals. The aim of the present study was to determine whether there is a relationship between citation factors and a trial's methodological quality using published randomised trials in lung cancer clinical research. Material and methods All of the randomised trials included in nine systematic reviews performed by the European Lung Cancer Working Party (ELCWP) were assessed using two quality scales (Chalmers and ELCWP). RESULTS: One hundred and eighty-one articles were eligible. The median overall ELCWP and Chalmers quality scores were 61.8% and 49.0%, respectively, with a correlation coefficient (r(s)) of 0.74 (P <0.001). A weak association was observed between citation factors and quality scores with the respective correlation coefficients ranging from 0.18 to 0.40 (ELCWP scale) and from 0.21 to 0.38 (Chalmers scale). American authors published trials significantly more often in journals with high citation factors than European or non-American authors (P <0.0001), despite no better methodological quality. Positive trials, which were significantly more likely to be published in journals with higher citation factors, were of no better quality than negative ones. CONCLUSION: Journals with higher citation factors do not appear to publish clinical trials with higher levels of methodological quality, at least for trials in the field of lung cancer research.

Chi-Square Distribution↗
PubMed2002

A phase II study testing paclitaxel as second-line single agent treatment for patients with advanced non-small cell lung cancer failing after a first-line chemotherapy.

The purpose of this study was to determine the activity of paclitaxel as a second-line chemotherapy for non-small cell lung cancer (NSCLC). This multicentric trial included patients who had failed to a first-line chemotherapy with platinum derivatives and/or ifosfamide. After registration, patients were treated by paclitaxel i.v. at a dose of 225 mg/m(2) given over 3 h administered every 3 weeks. Response was assessed after three courses of therapy. Sixty-seven patients were registered, one was ineligible and 64 were assessable for response. Two partial responses were observed (3% of the eligible patients; 95% confidence interval: 0-7%). No change was documented in 16 cases (24%). Tolerance was acceptable, the main toxicity being cumulative polyneuropathy. Median survival duration was 4.5 months with a 1-year rate at 19%. We concluded that paclitaxel is not active in terms of response as second-line chemotherapy for NSCLC.

Adult↗
PubMed2002

Role of granulocyte and granulocyte-macrophage colony-stimulating factors in the treatment of small-cell lung cancer: a systematic review of the literature with methodological assessment and meta-analysis.

In order to clarify the role of haematological colony-stimulating factors (CSF) in the treatment of small-cell lung cancer, we performed a systematic review of the randomised trials published on this topic. Since 1991, 12 studies were eligible, including a total of 2107 randomised patients. They were divided into three groups: (1) maintenance of dose-intensity when chemotherapy was given at conventional doses and time intervals (seven trials); (2) accelerated chemotherapy with increased dose-intensity by reducing the delay between chemotherapy cycles (five trials); (3) concentration of chemotherapy on an overall shorter duration time with a lower number of cycles (one trial). Before quantitative aggregation, we performed a methodological assessment using two previously published quality scales (Chalmers and ELCWP). The median quality scores for the pooled 12 trials was 59.9% (range: 42.2-82.0%) for the ELCWP scale and 55.8% (range: 38.0-76.8%) for the Chalmers scale. No statistically significant difference was observed between positive (significant) and negative (non-significant) studies allowing us to perform a meta-analysis. A detrimental effect on response rate was associated with CSF administration in the maintenance group (RR 0.92; 95% confidence interval [CI] 0.87-0.97) without significant effect on survival (HR 1.004; 95% CI, 0.89-1.13). In the accelerated group, no significant impact on response rate (RR 1.02; 95% CI, 0.94-1.09) or survival (HR 0.82; 95% CI, 0.67-1.00) was found. Although no difference in response rate was observed, a reduced survival was associated with concentrated chemotherapy. In conclusion, the published data do not support the routine use of haematological colony-stimulating factors in the treatment of small-cell lung cancer (SCLC).

Carcinoma, Small Cell↗
PubMed2002

A three-arm phase III randomised trial comparing combinations of platinum derivatives, ifosfamide and/or gemcitabine in stage IV non-small-cell lung cancer.

OBJECTIVE: To determine, in stage IV non-small-cell lung cancer (NSCLC), if the combination of gemcitabine-a new active drug-with ifosfamide (IG) or with the cisplatin-carboplatin association (CCG) will improve survival (primary end point) in comparison with a first-generation regimen, cisplatin-carboplatin-ifosfamide (CCI). PATIENTS AND METHODS: A total of 284 chemotherapy-naïve patients with metastatic NSCLC were randomised. Four were ineligible and 16 were not assessable for responses. Cisplatin was given at 60 mg/m2 on day 1, carboplatin AUC 3 mg.min/ml on day 1, ifosfamide 4.5 g/m2 on day 1 and gemcitabine 1 g/m2 on days 1, 8 and 15. Courses were repeated every 4 weeks. Response was assessed after three courses and chemotherapy was continued in responding patients until best response. There were 94 eligible patients in the CCI arm, 92 in CCG and 94 in the IG arm. RESULTS: The objective response rates for CCI, CCG and IG were 23% [95% confidence interval (CI) 15% to 32%], 29% (95% CI 20% to 39%) and 25% (95% CI 16% to 33%), respectively ( P = 0.61). Median survival time was 24, 34 and 30 weeks, respectively (P = 0.20). One-year survival was 23, 33 and 35%, and 2-year survival was 11, 14 and 17%, respectively. In some subgroups (older patients, women), there was a significant survival advantage for CCG and IG compared with CCI. Toxicity was tolerable: severe alopecia was less frequent in the CCG arm, and IG was associated with significantly more thrombopenia while CCG was associated with more leucopenia. CONCLUSION: In stage IV NSCLC, treatment with regimens including the new drug gemcitabine were associated with a better but not statistically significant observed survival compared with a classical first-generation cisplatin-containing regimen. The non-platinum combination of gemcitabine was as effective as its combination with platinum.

Adult↗
PubMed2002

A phase II randomised trial comparing the cisplatin-etoposide combination chemotherapy with or without carboplatin as second-line therapy for small-cell lung cancer.

BACKGROUND: A phase II randomised trial was performed with patients with SCLC to determine if the addition of carboplatin to cisplatin-etoposide might improve the response rate in second-line therapy. PATIENTS AND METHODS: Sixty-five eligible patients were randomised: 31 for CE (cisplatin 20 mg/m(2) and etoposide 100 mg/m(2) on days 1-3) and 34 for CCE (carboplatin 200 mg/m(2) on day 1, cisplatin 30 mg/m(2) on days 2-3, etoposide 100 mg/m(2) on days 1-3). RESULTS: Eighty-two per cent of these patients had an objective response to first-line therapy and, among responders, 63% had a treatment-free interval of >3 months after previous therapy. The best response rates were 29% [95% confidence interval (CI) 13-45] and 47% (95% CI 30-64) for CE and CCE, respectively, with median survival times of 4.3 and 7.6 months. Dose-intensity analysis revealed a significant improvement in the relative dose-intensity and etoposide absolute dose-intensity for CE. Toxicity was tolerable and comparable between the two study arms. CONCLUSION: CCE appears to be associated with a high objective response rate. The phase II randomised study design suggests that a comparison between the two regimens in a phase III trial would be interesting, but will probably be difficult to perform for reasons of accrual.

Adult↗
PubMed2002

The role of EGF-R expression on patient survival in lung cancer: a systematic review with meta-analysis.

The prognostic value of epidermal growth factor receptor (EGF-R) for survival of patients with lung cancer remains controversial. The authors performed a systematic review of the literature in order to clarify its impact. Published studies were identified using an electronic search in order to aggregate the available survival results, after a methodological assessment using a scale specifically designed by the European Lung Cancer Working Party (ELCWP). To be eligible, a study had to have dealt with EGF-R assessment in lung cancer patients on the primary site and to have analysed survival according to EGF-R expression. Among the 16 eligible studies, 14 assessed any nonsmall-cell lung cancer (NSCLC) subtype, one adenocarcinoma only and one squamous-cell carcinoma only. The overall median quality score was 56.3%, with no significant difference either between studies assessable or not assessable for meta-analysis or between studies with significant and nonsignificant results. One individual trial reported a survival benefit for patients with EGF-R expression, three a survival disadvantage and 12 no statistically significant difference. Eleven studies (2,185 patients) provided sufficient data to allow a meta-analysis of the survival results. EGF-R expression positivity was determined according to the cut-off as determined by the authors. The meta-analysis showed that EGF-R expression was not a statistically significant prognostic factor for survival in NSCLC. In the subgroup of studies using immunohistochemistry, statistical tests reached a significant level against EGF-R. Epidermal growth factor receptor might be a poor prognostic factor for survival in nonsmall-cell lung cancer. The amplitude of the impact is small, however, and may be subject to publication bias.

Adenocarcinoma↗
PubMed2002

[VEGF and survival of patients with lung cancer: a systematic literature review and meta-analysis].

The process of angiogenesis is an important factor in tumour development. One of the principal factors implicated in this process is vascular endothelial growth factor (VEGF) which induces, among other things, an increase in vascular permeability. We have undertaken a systematic review of the English and French literature in order to clarify its effect on the survival of patients with small cell (SCLC) and non-small cell (NSCLC) lung cancer. To be eligible studies had to deal with the the evaluation of VEGF or its receptors in lung cancer and describe the relationship of their expression to survival. The survival figures were subject to meta-analysis after a methodological evaluation by means of a specific numerical scale evaluating the design of the study, the methodology (including laboratory techniques), and the analysis of results. Among the 20 studies selected 15 identified VEGF expression, using univariate analysis, as a statistically significant indicator of poor prognosis. 17 reported sufficient data to allow aggregation of the survival figures, of which 15 were devoted to NSCLC (1,549 patients). The median overall methodological score was 48.3% (range 21.8-72.4%), without significant difference (p=0.63) between studies eligible or non-eligible for meta-analysis. The meta-analysis, using the authors' threshold of positivity for VEGF, showed that VEGF is an unfavourable prognostic factor in NSCLC (HR=1.48; 95% confidence interval 1.27-1.72). The data were insufficient to determine the prognostic value of VEGF in SCLC and that of its two receptors Flt-1 and KDR, with 1, 2 and 1 published studies respectively. In conclusion the expression of VEGF in MSCLC is a factor indicating a poor prognosis.

Carcinoma, Non-Small-Cell Lung↗
PubMed2001

Therapeutic use of granulocyte and granulocyte-macrophage colony-stimulating factors in febrile neutropenic cancer patients. A systematic review of the literature with meta-analysis.

The effectiveness of granulocyte and granulocyte-macrophage colony-stimulating factor (G-CSF and GM-CSF) in the treatment of febrile neutropenic cancer patients remains controversial. To assess their role in this condition, we conducted a systematic review of randomised trials published as full papers. A methodological evaluation using a specifically designed quality scale was performed before meta-analysis. Eleven trials were eligible, 8 of which were meta-analysable. The median quality score for the 11 pooled trials was 58.3% (range: 33.3%-68.8%). No significant quality difference was observed between positive (colony-stimulating factor more effective) and negative trials ( P=0.36). No quality difference was observed between the 8 meta-analysable studies and the 3 others, with respective median scores of 59.3% and 50%. No advantage was detected for the use of CSF in terms of mortality from febrile neutropenia, with a relative risk of 0.71 (95% CI 0.44-1.15). The relative risk was 0.66 (95% CI 0.39-1.13) in the G-CSF subgroup and 0.97 (95% CI 0.34-2.79) in the GM-CSF subgroup. Aggregation of the results on infection-related mortality, length of stay in hospital, fever and of neutropenia duration, antibiotic therapy adaptation and duration, superinfection rate and toxicity was not possible owing to the lack of adequate data in the publications. On the basis of this review, we cannot recommend the routine use of G-CSF or GM-CSF in established febrile neutropenia.

Anti-Bacterial Agents↗
PubMed2001

A three-arm phase III randomised trial assessing, in patients with extensive-disease small-cell lung cancer, accelerated chemotherapy with support of haematological growth factor or oral antibiotics.

The European Lung Cancer Working Party (ELCWP) designed a 3-arm phase III randomised trial to determine the role of accelerated chemotherapy in extensive-disease (ED) small-cell lung cancer (SCLC). Eligible patients were randomised between the 3 following arms: (A) Standard chemotherapy with 6 courses of EVI (epirubicin 60 mg m(-2), vindesine 3 mg m(-2), ifosfamide 5 g m(-2); all drugs given on day 1 repeated every three weeks. (B) Accelerated chemotherapy with EVI administered every 2 weeks and GM-CSF support. (C) Accelerated chemotherapy with EVI and oral antibiotics (cotrimoxazole). Primary endpoint was survival. 233 eligible patients were randomised. Chemotherapy could be significantly accelerated in arm B with increased absolute dose-intensity. Best response rates, in the population of evaluable patients, were, respectively for arm A, B and C, 59%, 76% and 70%. The response rate was significantly higher in arm B in comparison to arm A (P = 0.04). There was, however, no survival difference with respective median duration and 2-year rate of 286 days and 5% for arm A, 264 days and 6% for arm B and 264 days and 6% for arm C. Severe thrombopenia occurred more frequently in arm B but without an increased rate of bleeding. Non-severe infections were more frequent in arm B and severe infections were less frequent in arm C. Our trial failed to demonstrate, in ED-SCLC, a survival benefit of chemotherapy acceleration by using GM-CSF support.

Administration, Oral↗
PubMed2001

Prophylactic cranial irradiation in small cell lung cancer: a systematic review of the literature with meta-analysis.

PURPOSE: A systematic review of the literature was carried out to determine the role of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC). METHODS: To be eligible, full published trials needed to deal with SCLC and to have randomly assigned patients to receive PCI or not. Trials quality was assessed by two scores (Chalmers and ELCWP). RESULTS: Twelve randomised trials (1547 patients) were found to be eligible. Five evaluated the role of PCI in SCLC patients who had complete response (CR) after chemotherapy. Brain CT scan was done in the work-up in five studies and brain scintigraphy in six. Chalmers and ELCWP scores are well correlated (p < 0.001), with respective median scores of 32.6 and 38.8 %. This meta-analysis based on the available published data reveals a decrease of brain metastases incidence (hazard ratio (HR): 0.48; 95 % confidence interval (CI): 0.39 - 0.60) for all the studies and an improvement of survival (HR: 0.82; 95 % CI: 0.71 - 0.96) in patients in CR in favour of the PCI arm. Unfortunately, long-term neurotoxicity was not adequately described. CONCLUSIONS: PCI decreases brain metastases incidence and improves survival in CR SCLC patients but these effects were obtained in patients who had no systematic neuropsychological and brain imagery assessments. The long-term toxicity has not been prospectively evaluated. If PCI can be recommended in patients with SCLC and CR documented by a work-up including brain CT scan, data are lacking to generalise its use to any CR situations.

Brain Neoplasms↗
PubMed2001

The role of mitomycin in the treatment of non-small cell lung cancer: a systematic review with meta-analysis of the literature.

In order to clarify the role of mitomycin (MMC) in the treatment of NSCLC, we performed a systematic review of the literature and qualitatively assessed the selected studies using the ELCWP and Chalmers scales. 5 trials (202 patients) assessed the activity of MMC as single-agent chemotherapy in NSCLC. The overall response rate was 25% (95% Cl 19-31). In 10 randomized phase III trials (1769 patients), we studied the role of MMC in combination therapy. A meta-analysis, based on the available published data, failed to show any survival advantage of the MMC containing regimens (hazard ratio = 0.95; 95% Cl 0.83-1.10). Finally, 4 eligible trials (139 patients) assessed the activity of MMC regimens as salvage therapy, 3 in combination with vindesine and one with cisplatin and vinblastine. The overall response rate for the MMC-vindesine regimen was 10.5% (95% Cl 1.7-19.4). In conclusion, MMC is an active drug for NSCLC but does not improve survival when combined with other active drugs, particularly cisplatin. Its use for salvage therapy appears to be associated with marginal activity only.

Antibiotics, Antineoplastic↗
PubMed2001

Axonemal dynein intermediate-chain gene (DNAI1) mutations result in situs inversus and primary ciliary dyskinesia (Kartagener syndrome).

Kartagener syndrome (KS) is a trilogy of symptoms (nasal polyps, bronchiectasis, and situs inversus totalis) that is associated with ultrastructural anomalies of cilia of epithelial cells covering the upper and lower respiratory tracts and spermatozoa flagellae. The axonemal dynein intermediate-chain gene 1 (DNAI1), which has been demonstrated to be responsible for a case of primary ciliary dyskinesia (PCD) without situs inversus, was screened for mutation in a series of 34 patients with KS. We identified compound heterozygous DNAI1 gene defects in three independent patients and in two of their siblings who presented with PCD and situs solitus (i.e., normal position of inner organs). Strikingly, these five patients share one mutant allele (splice defect), which is identical to one of the mutant DNAI1 alleles found in the patient with PCD, reported elsewhere. Finally, this study demonstrates a link between ciliary function and situs determination, since compound mutation heterozygosity in DNAI1 results in PCD with situs solitus or situs inversus (KS).

Alleles↗
PubMed2001

Expression of IFN-gamma-inducible protein; monocyte chemotactic proteins 1, 3, and 4; and eotaxin in TH1- and TH2-mediated lung diseases.

BACKGROUND: Chemokines are involved in the influx of leukocytes into the airways in inflammatory lung diseases. The differential cell recruitment characteristic of T(H)1 versus T(H)2 immune responses may be associated with differential chemokine expression. OBJECTIVE: We investigated the expression of chemokines; monocyte chemotactic proteins (MCPs) 1, 3, and 4; eotaxin; and IFN-gamma-inducible protein 10 (IP-10) in both T(H)1- and T(H)2-mediated lung diseases. METHODS: By using immunocytochemistry and in situ hybridization, we examined the protein and mRNA expression, respectively, in bronchoalveolar lavage and biopsy samples in subjects with asthma, tuberculosis, sarcoidosis, and chronic bronchitis. RESULTS: Increased immunoreactivity and mRNA expression of IP-10 and of the MCPs was found in the bronchoalveolar lavage fluid and biopsy specimens of subjects with asthma and tuberculosis compared with that of control subjects (P <.005). IP-10, however, was particularly increased in subjects with sarcoidosis (P <.001). Eotaxin, on the other hand, was increased only in patients with asthma when compared with control subjects (P <.005). CONCLUSION: This study demonstrates that MCP-1, MCP-3, and MCP-4 expression is not specifically associated with lung diseases characterized by a particular cytokine profile. In contrast, IP-10 is mostly expressed in T(H)1-mediated diseases, and eotaxin expression seems to be specifically associated with lung diseases of a T(H)2 cytokine profile.

Chemokine CCL11↗
PubMed2001

Role of p53 as a prognostic factor for survival in lung cancer: a systematic review of the literature with a meta-analysis.

The role of p53, as a prognostic factor for survival in lung cancer, is controversial and the purpose of the present systematic review of the literature is to determine this effect. Published studies were identified with the objective to aggregate the available survival results after a methodological assessment using a scale specifically designed by the European Lung Cancer Working Party (ELCWP). To be eligible, a study had to deal with p53 assessment in lung cancer (primary site) only, and to provide a survival comparison according to the p53 status. Among the 74 eligible papers, 30 identified p53 abnormalities as a univariate statistically significant poor prognostic factor and 56 provided sufficient data to allow survival results aggregation. There was no significant difference between the trials that either showed or did not show a prognostic effect of p53 according to the methodological score or to the laboratory technique used. The studies were categorized by histology, disease stage, treatment and laboratory technique. Combined hazard ratios suggested that an abnormal p53 status had an unfavourable impact on survival: in any stage nonsmall cell lung cancer (NSCLC) the mean (95% confidence interval) was 1.44 (1.20-1.72) (number of studies included in the subgroup was 11), 1.50 (1.32-1.70) in stages I-II NSCLC (n=19), 1.68 (1.23-2.29) in stages I-IIIB NSCLC (n=5), 1.68 (1.30-2.18) in stages III-IV NSCLC (n=9), 1.48 (1.29-1.70) in surgically resected NSCLC (n=20), 1.37 (1.02-1.85) in squamous cell carcinoma (n=9), 2.24 (1.70-2.95) in adenocarcinoma (n=9), 1.57 (1.28-1.91) for a positive immunohistochemistry with antibody 1801 (n=8), 1.25 (1.09-1.43) for a positive immunohistochemistry with antibody DO-7 (n=16), and 1.65 (1.35-2.00) for an abnormal molecular biology test (n=13). Data were insufficient to determine the prognostic value of p53 in small cell lung cancer. In each subgroup of nonsmall cell lung cancer, p53 abnormal status was shown to be associated with a poorer survival prognosis.

Carcinoma, Non-Small-Cell Lung↗