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Biomedical subjects

I Monnet

Publications and source records attributed to I Monnet.

At least 19 recordsLinked to original sources
PubMed2002

Oxaliplatin plus vinorelbine in advanced non-small-cell lung cancer: final results of a multicenter phase II study.

BACKGROUND: Oxaliplatin and vinorelbine are both active agents against non-small-cell lung cancer (NSCLC). In a previous phase I trial, we showed that oxaliplatin (130 mg/m2, day 1) and vinorelbine (26 mg/m2/day, days 1 and 8) can be safely combined when given every 21 days. We completed the evaluation of this new platinum-based doublet in advanced NSCLC patients in a multicenter phase II study. PATIENTS AND METHODS: Twenty-eight chemotherapy-naïve patients (22 men and six women: median age 58 years, range 33-70), including 20 with stage IV disease, received this out-patient combination, with 5-hydroxytryptamine-3-receptor agonists as the only prophylactic measure. RESULTS: A total of 117 cycles were given, for a median of three per patient (range 1-8). Of 26 eligible patients, nine achieved a partial response (WHO criteria), giving an objective response rate of 35% [95% confidence interval (CI) 17% to 56%]. The median progression free survival was 5.0 months (95% CI 3.1 to 6.9), median overall survival was 9.8 months (95% CI 2.2 to 17.5) and the 1-year survival rate was 37%. Neutropenia was the principal toxicity, grade 4 occurring in 11 patients (39%) and 25 cycles (22%). Four patients (14%) experienced one episode of febrile neutropenia each. Acute oxaliplatin-related neurosensory toxicity was prevalent, but was mild to moderate in the majority of patients (82%) and reversible. Grade 1/2 vomiting (65% of patients) and diarrhea (32% of patients) were easily managed. CONCLUSIONS: The oxaliplatin-vinorelbine doublet is a safe and active out-patient combination. It may represent an interesting alternative in the management of patients with NSCLC, and serve as a new doublet to which other active agents could be added.

Adult↗
PubMed2002

Patterns of failure after prophylactic cranial irradiation in small-cell lung cancer: analysis of 505 randomized patients.

BACKGROUND: Prophylactic cranial irradiation (PCI) has a beneficial effect on overall survival in patients with small-cell lung cancer (SCLC) in complete remission as shown in a worldwide meta-analysis. The current analysis aimed to evaluate PCI effects on patterns of failure in this patient category. PATIENTS AND METHODS: The Institut Gustave-Roussy coordinated two parallel randomized studies including a total of 511 patients with SCLC. Patients were randomly assigned to either PCI (24 Gy in eight fractions and 12 days) or no PCI. Patterns of failure were analyzed according to (i) total event rates and (ii) isolated first site of relapse using a competing risk approach. RESULTS: Five hundred and five patients were analyzed. The 5-year cumulative rate of brain metastasis as an isolated first site of relapse was 37% in the control group and 20% in the PCI group (P < 0.001). The overall 5-year rates of brain metastasis were 59% and 43%, respectively [relative risk (RR) 0.50; P < 0.001]. The 5-year overall survival rates were 15% in the control group and 18% in the PCI group (RR 0.84; P = 0.06). CONCLUSIONS: PCI decreased significantly the risk of brain metastasis. Other events were not influenced. The relative death risk reduction was of borderline significance. Results reported as isolated first cause of failure and subsequent competing events may explain why a major treatment effect on brain metastases rate has a rather moderate effect on survival.

Adult↗
PubMed2001

Control of cell cycle progression in human mesothelioma cells treated with gamma interferon.

Recombinant human interferon gamma (r-hu-IFNgamma) exerts both antitumoral activity in the early stages of human malignant mesothelioma and a cytostatic effect in human mesothelioma (HM) cell lines in vitro. The antiproliferative effect of interferons (IFNs) reported in a variety of cells has been attributed to several mechanisms. In order to progress in the understanding of HM cell growth modulation by r-hu-IFNgamma, modifications of cell cycle progression and expression of key cell cycle regulator proteins in response to r-hu-IFNgamma were examined. Nine HM cell lines were studied, including one resistant to the antiproliferative effect of r-hu-IFNgamma. Except in the resistant cell line r-hu-IFNgamma produced an arrest in the G1 and G2-M phases of the cell cycle, associated with a reduction in both cyclin A and cyclin dependent kinase inhibitors (CDKIs) expression. Moreover cyclin B1/cdc2 activity was decreased. The present study provides the first evidence of a G2-arrest in r-hu-IFNgamma-treated HM cell lines and indicates that HM cell lines, despite their tumorigenic origin still support cell cycle control. The cell cycle arrest induced by r-hu-IFNgamma seems to depend on cyclin regulation through p21(WAF1/CIP1)- and p27(Kip1)-independent mechanisms and is not directly related to the induced DNA damage.

Antineoplastic Agents↗
PubMed2001

Phase I/II study of escalating doses of vinorelbine in combination with oxaliplatin in patients with advanced non-small-cell lung cancer.

PURPOSE: Oxaliplatin is a platinum compound active in non-small-cell lung cancer (NSCLC) patients, and vinorelbine (VNB) is an active reference agent. This phase I/II study was performed to determine the dose-limiting toxicity (DLT), the maximum-tolerated dose (MTD), and the recommended dose (RD) of a VNB/oxaliplatin combination given to previously untreated patients with advanced NSCLC. PATIENTS AND METHODS: Oxaliplatin was given at the fixed dose of 130 mg/m2 (2-hour intravenous [IV] infusion) on day 1. VNB was administered on days 1 and 8 (10-minute IV infusion), with doses starting at 22 mg/m2/d and escalated by 2 mg/m2 increments until MTD. Treatment was repeated every 3 weeks. No special hydration measures or prophylactic granulocyte colony-stimulating factors were used. RESULTS: Twenty-seven patients (20 men, 7 women) received 110 cycles total at six different VNB dose levels. Neutropenia was the DLT. Although no patient experienced DLT at the highest dose level (32 mg/m2/d), multiple treatment delays (54% of cycles) and dose reductions (34% of cycles) were required at this dose level. Others toxicities were mainly limited to grade 1 peripheral neuropathy and grade 1/2 nausea/vomiting. The relative dose-intensity of administered VNB from dose levels 3 to 6 (26 to 32 mg/m2) remained stable, whereas grade 3/4 neutropenia increased. All patients were assessable for activity; there were 10 objective responses, including one complete response (37% response rate). CONCLUSION: The present combination can be safely administered in an outpatient setting. The RD is VNB 26 mg/m2 days 1 and 8 with oxaliplatin 130 mg/m2 day 1 every 3 weeks.

Adult↗
PubMed2001

[Primary pleural lymphoma: a rare complication of tuberculosis pleural sequelae].

We report two cases of malignant lymphoma of B phenotype occurring after therapeutic pneumothorax for tuberculosis. In both cases, outcome was fatal without time for specific treatment. Mainly reported in Japan, this pathology seems to be less frequent in western countries. As for B phenotype lymphoma associated with immunodeficiency, association with Epstein Barr virus is reported. Definite diagnosis is difficult and requires surgical biopsy. Prognosis remains poor with a survival ranging from 3 to 6 month.

Aged↗
PubMed2000

Cytochrome c oxidase deficiency in the muscle of patients with zidovudine myopathy is segmental and affects both mitochondrial DNA- and nuclear DNA-encoded subunits.

Zidovudine (AZT) can induce a mitochondrial disorder associated with mitochondrial (mt) DNA depletion affecting skeletal muscle, heart, and liver. Zidovudine myopathy is characterized by ragged-red fibers and partial cytochrome c oxidase (COX) deficiency. We evaluated at a single fiber level the expression of COX II (mtDNA-encoded) and COX IV (nuclear DNA-encoded) subunits in 12 HIV-infected patients with zidovudine myopathy. We also evaluated COX activity on longitudinal muscle sections in one patient. In all patients, evaluation of the expression of COX II and COX IV subunits showed focal deficiency. All fibers negative for COX II or COX IV were negative by COX histochemistry; 32-92% (median 61%) of COX-negative fibers were negative for COX II antigens, and 7-58% (median 28%) were negative for COX IV antigens. One hundred and thirty-nine of 317 COX-negative fibers 139 (43.8%) were selectively negative for COX II; 28 of 317 (8.8%) COX-negative fibers were selectively negative for COX IV. A study of longitudinal distribution of COX activity demonstrated that COX deficiency was segmental with blurred borders, as previously observed in patients with myoclonus epilepsy with ragged-red fibers. We conclude that proteins encoded by mtDNA are predominantly, but not exclusively, involved in zidovudine myopathy. Our results confirm the value of single muscle fiber evaluation in the assessment of mitochondrial abnormalities related to zidovudine.

Chromosomes↗
PubMed2000

Expression of the genetic variants of human alpha-1-acid glycoprotein in cancer.

OBJECTIVES: We have investigated the AAG and its genetic variants concentrations in plasma samples of 61 patients suffering from different types of cancers. DESIGN AND METHODS: The patients were shared out in three groups, breast, lung, and ovary cancers groups. AAG concentration was measured by an immunonephelometric method and the phenotype was determined, after desialylation of plasma by analytical isoelectric focusing. Detection of AAG variants was made by immunoblotting and their proportions were determined by laser densitometry analysis. A population of 74 healthy individuals served as controls. RESULTS: The plasma concentrations of AAG in the breast and lung cancer groups were 2.5 times increased, while in the ovary cancer group, the concentrations were 1.6 times increased. AAG concentrations in the cancer population ranged between 0.45 and 2.85 g/L (mean value 1.12 +/- 0.51 g/L). The proportions of the ORM1 and ORM2 variants were similar to those in the healthy population. In breast and lung cancer groups, the relative concentrations of genetic variants were increased more than 2.5 fold, whereas a 1. 6-fold increase was observed in the ovary cancer group. CONCLUSIONS: These results show that AAG plasma concentrations are increased in these types of cancers and that changes in the expression of the genetic variants of AAG could also occur according to the type of cancer.

Adult↗
PubMed2000

Use of tumor markers for differential diagnosis of mesothelioma and secondary pleural malignancies.

STUDY OBJECTIVE: The aim of the study was to assess diagnosis value of tumor markers for differential diagnosis between mesothelioma and other pleural tumors. DESIGN AND METHODS: Prospective study of 85 patients attending our hospital with malignant pleural effusion. The diagnostic approach involved routine pleurocentesis followed by pleural needle. When precise diagnosis was not achieved, thoracoscopy with pleural biopsies was performed. Carcinoembryonic antigen (CEA), hyaluronic acid, tissue polypeptide antigen and cyfra 21 to 1 were measured in serum and pleural fluid. RESULTS: By using receiver operating characteristics curves and area under curves, the best diagnostic characteristics were obtained with pleural and serum CEA concentrations. The area under the curve was larger for pleural ACE than for serum ACE. The sensitivity and specificity of a pleural CEA level exceeding 3 ng/mL for ruling out the diagnosis of mesothelioma were 100% and 77%, respectively. CONCLUSION: A CEA level above 3 ng/mL in pleural fluid eliminated the diagnosis of mesothelioma, whereas the other markers were not sufficiently discriminant. However, despite a negative predictive value of 100% at a cutoff of 3 ng/mL, CEA assay in pleural fluid only avoids a small number of diagnostic thoracoscopies.

Adenocarcinoma↗
PubMed2000

[Unusual cause of severe alveolar hypoventilation].

Mesenteric panniculitis is a rare disease of the adipose tissue of mesentery. Ascites is an unusual presentation. We report a case of panniculitis whose initial presentation was an obesity-hypoventilation syndrome with pulmonary hypertension. Respiratory disorders were related to abundant ascites. Panniculitis cure and ascites disappearance allowed return to normal pulmonary function and pulmonary artery pressure.

Aged↗
PubMed2000

[Evaluation of occupational exposures in lung cancer].

Occupational lung cancers are underestimated by the number of cases compensated in the French National Insurance System. Rules of compensation of occupational diseases were recently modified in France. Therefore a study was conducted on incident cases of lung cancer in a general hospital in the Paris area. The aim was to evaluate the exposure to carcinogens using data of a detailed specific occupational questionnaire, and to determine the number of cases who could receive compensation. Two hundred and seven subjects (171 males, 36 females, mean age = 64.5 years) were eligible in 1996, and 122 had an occupational questionnaire. Definite exposure to one or more occupational carcinogens in at least one job was identified in 50 subjects, the most frequent agent was asbestos (42 subjects). Claim for compensation was done in 32 subjects, mainly for asbestos (30 subjects). This study emphasizes the frequency of occupational exposure to carcinogens, and the usefulness of systematic occupational questionnaire in subjects having lung cancer. Social and financial consequences are important for these subjects. Further studies are needed, with recruitement of control subjects to allow calculation of the attributable risk to occupational factors in lung cancer.

Aged↗
PubMed1999

[Malignant mesothelioma: clinical and therapeutic study].

Like lung cancer, mesothelioma is difficult to diagnose early. Nevertheless disease stage is the determinant factor for outcome of treatment. Effective diagnostic examinations must be undertaken promptly. Thoracoscopy is one of the best diagnostic procedures provided that it is skillfully performed to prevent complications such as development of subcutaneous nodules along the pathway of the trocar. Several arguments have been proposed against routine screening including low incidence of the disease, poor sensitivity and specificity of screening techniques, and lack of effective therapy documented by phase III study. However there are a number of arguments in favor of screening. The high-risk population is well defined. Although no control study is currently available, promising new results have been observed in limited forms, i.e., 62% response rate at stage IA with 39% survival at 5 years in patients presenting epithelial forms without lymph node involvement treated by pleuro-pneumonectomy, chemotherapy, and radiotherapy. Screening is necessary to recruit more early-stage patients for further clinical trials to improve therapeutic techniques. Poor outcome of treatment could be due to delayed diagnosis. Early diagnosis is also needed to allow compensation of occupational disease to begin while the patient is still alive.

Adult↗
PubMed1998

Human malignant mesothelioma cell growth: activation of janus kinase 2 and signal transducer and activator of transcription 1alpha for inhibition by interferon-gamma.

Intrapleural injections of recombinant human IFN-gamma have shown some efficacy in reducing tumor growth in early stages of diffuse malignant mesothelioma (DMM). Here, we have addressed the potential therapeutic effect of IFN-gamma in DMM by investigating the activation of the JAK/STAT signaling pathway in seven human mesothelioma cell lines (HMCLs) that were differentially responsive to the antiproliferative activity of IFN-gamma. We showed that janus kinase 2 (JAK2) and signal transducer and activator of transcription 1 (STAT1) were phosphorylated on tyrosine residues within 15 min in all the HMCLs in which IFN-gamma (500 units/ml) inhibited proliferation. In addition, STAT1 binding activity to the gamma-activated sites DNA sequence was detected within 15 min in electrophoretic mobility-shift assay analysis, and IFN regulatory factor-1 RNA expression was observed within 6 h in the more responsive cells (72.7-95.2% inhibition of DNA synthesis after 72 h of treatment). Conversely, in several HMCLs, absent or limited growth suppressive effect (less than 22% inhibition of DNA synthesis) was associated with alterations in expression or activation of JAK2 or STAT1 or, downstream, with low induction of IFN regulatory factor-1 RNA expression and/or STAT1 protein expression following IFN-gamma treatment. These data suggest that at least part of the IFN-gamma effect on proliferation of HMCLs is mediated directly through activation of the JAK/STAT1 signaling pathway, and it could account for the antitumoral activity reported in DMM patients treated with IFN-gamma.

Cell Division↗
PubMed1998

Controlled clinical trial of prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission.

We conducted a randomised clinical trial on 211 patients with small-cell lung cancer in complete remission (CR). The aim of this trial was to evaluate the effect of prophylactic cranial irradiation (PCI) on overall survival. Eligible patients were randomly assigned to receive either PCI (100 patients) or no PCI (111 patients). Each centre was allowed to use its own PCI protocol as long as the total dose was within the range of 24-30 Gy and delivered in less than 3 weeks with fractions of 3 Gy or less. The mean follow-up is 5 years. The survival curves do not differ significantly (P = 0.25) between the two groups. The 4-year overall survival rate (95% confidence interval) is 22% [15-32%] in the PCI group versus 16% [10-25%] in the control group. The relative risk of death in the PCI group compared to the control group is 0.84 (95% CI = [0.62-1.13]). The incidence of brain metastasis is lower in the PCI group, but the difference is not statistically significant (P = 0.14). The 4-year cumulative rate of brain metastasis is 44% [32-57%] in the PCI group compared to 51% [38-63%] in the control group. In conclusion, in this study, which had to be closed prematurely, no significant difference was found in terms of the incidence of brain metastases nor in survival.

Adult↗
PubMed1998

Phase II study of oxaliplatin in poor-prognosis non-small cell lung cancer (NSCLC). ATTIT. Association pour le Traitement des Tumeurs Intra Thoraciques.

The aim of this phase II study was to determine the antitumour activity and safety of trans-1-diaminocyclohexane-platinum (oxaliplatin) in previously untreated advanced non-small cell lung cancer (NSCLC) patients. 33 patients with unresectable and measurable NSCLC were entered into this phase II study between January 1992 and January 1994. Patients had either locoregional disease with performance status 2 (19 patients) or a stage IV disease (14 patients). Oxaliplatin (130 mg/m2) was given on an out-patient basis (2-h infusion, every 21 days) without hydration. Response was assessed after every two courses. One hundred courses were administered, with a mean of three courses per patient (range 1-12). All patients were evaluable for response; 1 had a complete response, and 4 a partial response (overall response rate 15%, 95% confidence interval 5.1-31.9%). The median response duration was 5.9 months. All cycles (n = 100) were evaluable for toxicity assessment. Transient reversible, cold-related finger dysesthesias occurred in 29 patients, but were mild, and disappeared in most cases within a few days. We observed brief episodes of pharyngolaryngeal discomfort (8 patients, 11 episodes) accompanied in 4 cases (3 patients), by transient episodes of inspiratory stridor, leading 2 patients to treatment withdrawal. We conclude that oxaliplatin has activity in poor-prognosis NSCLC and that this treatment is feasible in out-patients; the absence of renal and haematological toxicity makes this drug a good candidate for further evaluation in NSCLC.

Aged↗