Biomedical subjects

C Mascaux

Publications and source records attributed to C Mascaux.

31 records · Page 2Linked to original sources

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

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

Biological basis of anemia.

Anemia is a frequent complication in cancer, occurring in more than 50% of patients with malignancies. Several factors can cause anemia in these patients, such as blood loss, hemolysis, bone marrow infiltration, hypersplenism, and nutrient deficiencies. However, in a considerable number of patients, no cause other than malignant disease itself can be implicated. This cancer-related anemia is similar to the anemia observed in other chronic diseases, such as rheumatoid arthritis and some chronic infections. The syndrome of anemia of chronic disease is characterized by a hyporegenerative, normocytic, normochromic anemia associated with reduced serum iron and transferrin saturation but elevated (or normal) ferritin levels. Cancer-related anemia results from activation of the immune and inflammatory systems, leading to increased release of tumor necrosis factor, interferon-gamma, and interleukin-1. The cytokine-mediated relative failure of erythropoiesis has been further investigated, and three different mechanisms of action are proposed: (1) impaired iron utilization; (2) suppression of erythroid progenitor cells differentiation; and (3) inadequate erythropoietin production. In addition, the life span of red blood cells is shortened in cancer-related anemia and production cannot compensate sufficiently for the shorter survival time. Administration of recombinant human erythropoietin (r-HuEPO, epoetin alfa) can not only correct inadequate endogenous erythropoietin production, but also can overcome the suppression of erythroid progenitor cells and impairment of iron mobilization.

Anemia↗

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↗

PubMed2001

[The role of chemotherapy in the treatment of non-metastatic, non-small cell bronchial cancers].

A systematic review of the literature about the role of chemotherapy in comparison to local therapies--surgery or radiotherapy--in non-small cells lung cancers has identified 35 randomised trials. The methodological assessment has not shown significant difference for quality scores between negative or positive studies in term of survival effect. The aggregation (meta-analysis) shows a significant effect of survival improvement by chemotherapy, whatever all indications are considered or subgroups like adjuvant chemotherapy to surgery, neoadjuvant chemotherapy, concomitant radio-chemotherapy and induction chemotherapy prior to thoracic irradiation.

Belgium↗

PubMed2000

A systematic review of the role of etoposide and cisplatin in the chemotherapy of small cell lung cancer with methodology assessment and meta-analysis.

PURPOSE: Cisplatin (CDDP) and etoposide (VP16) are considered major standard cytotoxic drugs for small cell lung cancer (SCLC). The present systematic review had as its objective the evaluation of their role, as components of chemotherapy regimens, on survival. METHODS: Published randomised clinical trials (from 1980 to 1998) were selected comparing, in SCLC patients, chemotherapy regimens, given as first-line therapy. One arm (the experimental arm) had to include CDDP and/or VP16, while another had to omit the same drug(s). Trials quality was assessed by two published scores (Chalmers and European Lung Cancer Working Party (ELCWP)). For each individual trial, the hazard ratio (HR) of the survival distributions was estimated on the basis of reported statistics or, if not available, by extracting, from the survival graphical representations, the data required to construct the difference between expected and observed numbers of events as calculated in the log-rank statistic. A combined hazard ratio was obtained by the Peto method (a value < 1 meaning a benefit for CDDP and/or VP16). RESULTS: Thirty-six trials eligible for our systematic review were identified, classified into four groups (I-IV): group I, 1 trial testing a CDDP-based regimen (without VP16) against another arm not including either CDDP or VP16; group II, 17 trials testing a VP16-based regimen (without CDDP) against a regimen without VP16 and CDDP; group III, nine trials comparing a regimen including CDDP and VP16 with a regimen using neither drug; and, finally, group IV, nine trials comparing a regimen based on both drugs with a regimen based on VP16 only. Overall, Chalmers and ELCWP scores correlated well (r(S) = 0.76, P < 0. 001) and had respective median scores of 50.3 and 63.7%. The number of eligible patients did not have a significant impact on the scores as well as the trials group, the trial positivity (a positive trial defined as showing itself a statistically significant survival benefit for the experimental regimen), overall or in categories, and the year of publication. Combined hazard ratios with 95% confidence intervals were: 0.70 (0.41-1.21) for group I, 0.72 (0.67-0.78) for II, 0.57 (0.51-0.64) for III, and 0.74 (0.66-0.83) for IV, showing a survival benefit in favour of regimens including etoposide alone or in combination with cisplatin, justifying with high significance levels the use of each of these drugs. Overall survival benefits could also be shown for regimens including CDDP (HR = 0.61; confidence interval (CI), 0.57-0.66), as well as for those including VP16 (HR = 0. 65; CI, 0.61-0.69). Robustness of these results has to be confirmed with appropriate randomised trials.

Antineoplastic Agents, Phytogenic↗

PubMed2000

[Hemoptysis].

An 82 years-old man is admitted for suspicion of bronchial cancer. He has a persistent cough, repeated bronchial infections and haemoptysis. On thoracic CT-scan, there is an increased thickness of the bronchial walls situated at the tracheobronchial cross.

Aged↗

PubMedDate not supplied

Phase II and III studies with new drugs for non-small cell lung cancer: a systematic review of the literature with a methodology quality assessment.

We carried out a systematic review of new drugs active in non-small cell lung carcinoma (NSCLC). Fifty five phase II and III trials were reviewed (vinorelbine (19 trials), paclitaxel (15), gemcitabine (11), docetaxel (6), topotecan (2) or irinotecan (2)). The first four ones could be considered as active drugs when given as single agent. More information is required for the camptothecin derivatives. Four phase III randomised studies were available, all concerning vinorelbine. They showed that in combination with cisplatin, vinorelbine improved the response rate and perhaps survival, in comparison to vinorelbine alone and that vinorelbine was better than 5 fluorouracil and vindesine. A quantitative overview was impracticable, because of too few randomised trials. A qualitative overview was carried out using the European Lung Cancer Working Party score. The overall median quality score was 65.3%. There was no statistically significant difference between the drugs, but there was a positive correlation between the score and the number of patients. There was also an improvement of the quality score in favour of the randomised trials. Some important methodological aspects were often missing in the articles. In conclusion, gemcitabine, vinorelbine, paclitaxel and docetaxel are active against NSCLC but more good-quality data are required to define their exact role in the routine.

Antineoplastic Agents↗

PubMedDate not supplied

Expression of p53 in preneoplastic and early neoplastic bronchial lesions.

p53 alteration has been reported to be an early event in bronchial carcinogenesis. Our study purpose was to determine the rate of p53 expression in the various preneoplastic and early neoplastic bronchial lesions obtained by biopsy during fluorescence bronchoscopy and to analyse its association with patients characteristics. Various stages of preneoplastic lesions as well as radio-occult lung cancer were studied in biopsies obtained by fluorescence bronchoscopy. We assessed the expression of p53 by immunohistochemistry using monoclonal antibody clone DO7. The p53 expression was considered as positive if > or = 1% of cells were positive and the level of positivity was expressed in percentage of positive cells. Fourteen patients were included in each category of preneoplastic lesions. At the threshold of 1% of positive cells p53 expression was observed in 28.5% of the patients with a histologically normal epithelium. This number of positive patients increased with the severity of preneoplastic lesions and reached 100% in the mild dysplasia. The mean rates of p53 positive cells for normal epithelium, hyperplasia, metaplasia, mild and severe dysplasia, carcinoma in situ and invasive radio-occult carcinoma were respectively 0.9, 3.4, 9.1, 20.5, 50.2, 34.7 and 42.5%. There was no statistically significant correlation between p53 expression and patient characteristics such as sex, age, smoking habits and indication for fluorescence bronchoscopy. The alteration of p53 expression in patients with high risk of lung cancer was an early event: this abnormality increased with the severity of the lesions, without significant correlation with patient characteristics.

Adult↗

PubMedDate not supplied

Expression of thrombospondin in non-small cell lung cancer.

OBJECTIVE: Initially considered as an inhibitor of angiogenesis, the role of thrombospondin is currently controversial. The primary purpose of our study was to determine the expression of thrombospondin (TSP) in invasive lung tumours. The secondary objectives were to investigate its relationship with other factors related to angiogenesis and to assess their clinicopathological significance. MATERIALS AND METHODS: From January 1993 to September 1998, we collected non-small cell lung cancer (NSCLC) and normal nearby-matched tissues from surgical specimens of 64 patients. Using these specimens, we assessed the expression of TSP by immunohistochemistry with monoclonal antibody to human TSP (clone 11.4). This expression was also correlated with other factors directly or indirectly related to angiogenesis:p53, Ki-67 as proliferation factor and microvessel count determined with anti-CD-31 antibody. RESULTS: The resected tumours (stages I-IIIB) consisted of 30 adenocarcinomas, 24 squamous cell carcinomas, 5 bronchioalveolar carcinomas, 4 adenosquamous carcinomas and 1undifferentiated NSCLC. The mean values of TSP expression in neoplastic and normal related tissues were 63.08% and 86.57 %, respectively. This difference was statistically significant (p = 0.02). There was a higher level of variability of TSP expression between tumours than between normal tissues. The expression of TSP in NSCLC was statistically correlated to the expression of TSP in normal matched tissues (coefficient correLation rate = 0.31, p<0.01). The median expression of p53, Ki-67 and microvessel count in tumours was 45.00%, 38.80% and 8.33%, respectively. The correlations between TSP and the other biological variables and between these latter variables themselves were not statistically significant. No statistically significant difference was observed in survival according to TSP expression. CONCLUSION: TSP appeared to be decreased in NSCLC in comparison with normal matched tissue. The TSP expression was not correlated with the other studied variables and was not associated with a significant difference in survival.

Adult↗

PubMedDate not supplied

[Docetaxel as salvage treatment for non-small cell lung cancer: implementation study].

Salvage treatment with docetaxel after failure of cisplatin-based chemotherapy in non-small cell lung cancer (NSCLC) has already been tested in the context of clinical prospective trials but only dealing with selected patients. The aim of the present study is to assess the generalizability of these results in an unselected population. We retrospectively analysed the data of all patients not included in clinical studies and treated at the Jules Bordet Institute between September 1996 and July 2003 by docetaxel after a previous chemotherapy containing platinum. Patients were separated in two groups: eligible or not studies according to the selection criteria of the published phase II and III prospective trials. There were 27 patients treated by docetaxel after relapse or failure of prior first-line platinum-based chemotherapy. Among them, 15 were ineligible according to the criteria of published phase II and III trials. The global response rate was 7.41%. All responders had a partial response to first line chemotherapy. Toxicity consisted mainly in grade III/IV neutropenia and was similar between the two group of patients. The median survival time was 25 weeks. In conclusion, our implementation study confirms the activity of docetaxel as salvage therapy after failure of first line cisplatin-based chemotherapy in an unselected population of patients with NSCLC, with a response rate similar to that obtained in propective trials.

Adult↗

PubMedDate not supplied

EGFR, c-erbB-2 and ki-67 in NSCLC and preneoplastic bronchial lesions.

BACKGROUND: The relationships between EGF-R and c-erbB-2 with other factors involved in tumour regulation are not well understood. The aim of this study was to correlate the expression of these markers with tumour proliferation. MATERIALS AND METHODS: The presence of EGF-R, c-erbB-2 and Ki-67 was evaluated by immunohistochemistry in non-small cell lung cancer (NSCLC) and preneoplastic lesions. RESULTS: Forty-two percent of the tumours were positive for EGF-R, 22% for c-erbB-2 and 97% for Ki-67. No statistically significant correlation was found between EGF-R and Ki-67, EGF-R and c-erbB-2 or between c-erbB-2 and Ki-67. With regards to Ki-67, a significant difference in survival was noted in favour of patients who did not express the marker. In preneoplastic lesions, most of the low-grade lesions showed neither EGF-R nor Ki-67 staining. In contrast, most of the high-grade lesions stained positively for these proteins. CONCLUSION: EGF-R and c-erbB-2 do not seem to be correlated with Ki-67 in NSCLC.

Adult↗