Treatment outcome and survival in participants of phase I oncology trials carried out from 2003 to 2006 at Institut Gustave Roussy.

BACKGROUND: The oncology community usually perceives phase I oncology trials as associated with poor or limited benefits and substantial risks. There is scarce data concerning outcome and survival of patients enrolled in current phase I oncology trials. PATIENTS AND METHODS: We reviewed all phase I oncology trials conducted by investigators from the Adult Phase I Unit at Institut Gustave Roussy from 2003 to 2006. We report data concerning patient demographics, treatment outcome, toxicity, survival and type of care after trial exit. RESULTS: We analyzed 10 trials involving 180 participants. The overall response rate was 7.2%. Disease control (objective response plus stable disease) was achieved in 48.2% of patients. The rate of toxic death was 0.5%. In all, 38% of patients had at least one episode of grade 3 or 4 toxic events. The median progression-free survival and the median overall survival (OS) were 2.3 and 8.7 months, respectively. On multivariate analysis, a time between diagnosis of disease and inclusion in the phase I trial > or =24 months and evidence of disease control were statistically significant predictors of improved OS. CONCLUSION: Current phase I oncology trials are safe and are associated with clinical benefit in a substantial proportion of patients.     

Percutaneous ethanol injection vs. resection in patients with small single hepatocellular carcinoma: a retrospective case-control study with cost analysis

BACKGROUND: Percutaneous ethanol injection and hepatic resection are the most widely used curative therapeutic options for patients with compensated liver disease and small hepatocellular carcinoma. AIM: To compare percutaneous ethanol injection and hepatic resection in a selected group of consecutive French patients with a single hepatocellular carcinoma, smaller than or equal to 50 mm, in terms of survival, recurrence rate of malignancy and direct costs. METHODS: The analysis of two contemporary cohorts of Child-Pugh A or B patients with a single hepatocellular carcinoma of < or = 50 mm treated by percutaneous ethanol injection (n=55) or hepatic resection (n=50). RESULTS: Long-term survival was not significantly different between the two groups when the size of hepatocellular carcinoma was less than 30 mm. However, the survival of patients with hepatocellular carcinoma larger than 30 mm was higher after hepatic resection than after percutaneous ethanol injection (P=0.044). The cumulative direct costs were significantly higher in patients treated by hepatic resection than in those treated by percutaneous ethanol injection regardless of the tumour size. The calculated costs per month of survival in patients treated with percutaneous ethanol injection and hepatic resection were 999 vs. 3865 euros, respectively (P < 0.001). CONCLUSIONS: Percutaneous ethanol injection is more cost effective than hepatic resection in patients with a single hepatocellular carcinoma smaller than 30 mm. However, in patients with a larger tumour, long-term survival is higher after hepatic resection.     

The potential risk factors leading to peptic ulcer formation in autoimmune disease patients receiving corticosteroid treatment

AIM: To study the potential risk factors leading to peptic ulcer disease among autoimmune disease patients on corticosteroid treatment. METHODS: One hundred and thirty-eight corticosteroid-treated autoimmune disease patients were enrolled; their demographic data were recorded and laboratory data were measured. Endoscopy was performed to assess the occurrence of peptic ulcer disease. Helicobacter pylori infection was diagnosed on the basis of rapid urease test and histological examination. RESULTS: Twenty-eight (20%) of 138 autoimmune disease patients had peptic ulcer disease, including 17 with gastric ulcer, eight with duodenal ulcer and three with gastric ulcer plus duodenal ulcer. Eighty five (62%) had used non-steroidal anti-inflammatory drugs and 46 (33%) had H. pylori infection. The majority of peptic ulcer disease subjects showed the following characteristics: age >or= 60 years; male; smokers; non-steroidal anti-inflammatory drug users, particularly the non-specific cyclo-oxygenase inhibitors; presence of hyperpepsinogenaemia I; low H. pylori colonization (P < 0.05). Multivariate analysis revealed that an age >or= 60 years [odds ratio (OR), 6.80; P = 0.001], smoking (OR, 7.94; P = 0.004) and the use of non-specific cyclo-oxygenase inhibitors (OR, 4.71; P = 0.030) were the predominant risk factors for the development of peptic ulcer disease among these patients, whereas H. pylori infection showed a protective role (OR, 0.20; P = 0.022). CONCLUSIONS: Old age, smoking and the use of non-specific cyclo-oxygenase inhibitors are risk factors for peptic ulcer disease in autoimmune disease patients on corticosteroid treatment. H. pylori infection appears to protect against peptic ulcer disease in these patients.     

Decreased white blood cell counts in semiconductor manufacturing workers in Taiwan

Objectives: To assess the systematic health effects on the liver, kidney, and haematological function tests of workers in semiconductors in Taiwan.

Methods: 926 workers of a semiconductor plant in Taiwan in July 1995 were investigated. Complete blood tests including liver, kidney, and haematological functions were available from 227 workers.

Results: There was a significantly lower mean (SD) white blood cell (WBC) count in male workers of photolithography (5870 (1190)/mm³, p=0.003) and implantation (6190 (1150)/mm³, p=0.018) than that of male control workers (7350 (1660)/mm³). There was a significantly higher prevalence of leukopenia in male photolithography workers (6 of 20; 30%) than in male control workers (1 of 18; 5.6%), the crude odds ratio (OR) was 7.3 (95% confidence interval (95% CI) 1 to 55.6), and the multivariate adjusted OR was 8.1 (95% CI 0.83 to 78.3). The tests for serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), γ glutamyl transferase (RGT), and creatinine were not significant among male workers. Female workers in photolithography had abnormal SGPT and RGT of borderline significance, the multivariate adjusted ORs were 9.6 (95% CI 0.86 to 107) and 6.35 (95% CI 0.53 to 75.8), respectively.

Conclusions: This study suggests that leukopenia is a potential health effect in male fabrication workers of the semiconductor industry. The tasks of the process, maintenance, and equipment engineers which consisted mostly of men put them at risk for intermittent short term peak exposure to glycol ethers, ionising radiation, arsenic, or other toxins. The findings of this medical surveillance are significant; however, a further investigation of the aetiological factors and the subsequent health effects is necessary.

     

Attitudinal classification of patients receiving antibiotic treatment for mild respiratory tract infections

The aim of this study was to determine patients’ perceptions of antibiotic therapy and the doctor's skill in the management of ambulatory respiratory tract infections. Standardized face-to-face interviews were used with more than 3000 randomized patients or parents from four European countries. Attitudinal dimensions relating to their doctor identified four patient types: Involved (30%), Deferent (23%), Ignored (13%) and Critical (17%). Involved and Deferent patients were the most satisfied by the information received from their doctor (43%/39% compared with 17%/16% for Ignored/Critical, respectively, P<0.01). They also scored more highly on the accurate use of antibiotics, with 80%/80% vs. 38%/62%, respectively (P<0.01), understanding dosing intervals and 77%/77% vs. 36%/60% (P<0.01), understanding the course length. Involved and Deferent patients showed better compliant behaviour, with 91% of both groups vs. 86% of the Ignored and Critical claiming to have taken every dose (P<0.001) and 92%/87% vs. 84%/85% claiming to have finished the course (P<0.001 for Involved only). Involved and Deferent patients were less prone to save part of a course of antibiotics than the Ignored and Critical (46%/41% vs. 20%/31%, P<0.001), and they perceived the antibiotics prescribed to be more effective (36%/31% vs. 21%/15%, P<0.001). By analysing patient perceptions, this study identifies an important mirror effect, whereby a more sympathetic attitude from the doctor should increase the patient's involvement in disease management, for a more appropriate use of antibiotics in common infections.     

Effectiveness of a measurement feedback system on outcome in rheumatoid arthritis: a controlled clinical trial

BACKGROUND: With the help of a measurement feedback system, the treatment strategy for individual patients with rheumatoid arthritis (RA) can be adjusted to achieve optimal control of disease activity. OBJECTIVE: To study whether a measurement feedback system is effective in reducing disease activity in patients with RA. METHODS: Forty eight rheumatologists and 264 patients participated in a controlled clinical trial. A three month control period was followed by a 12 month period, where feedback on disease activity, disability, and damage was provided to the rheumatologist. The primary outcome measure was the rheumatoid arthritis disease activity index (RADAI). RESULTS: The feedback system was used for 142/228 (62%) patients. Disease modifying antirheumatic drug changes occurred in 69/169 (41%) patients. In patients with high disease activity and feedback use (n=70), the RADAI decreased in the feedback period by -0.27 points per 30 days (p<0.05), as compared with the control period. Patients for whom the feedback system was used had a better outcome than non-users. CONCLUSION: Much more training on the use of a feedback system and outcome measures, as well as the inclusion of explicit treatment guidelines will be necessary to increase the clinical use of measurement feedback and, possibly, to reduce disease activity for a larger number of patients with RA.     

Treatment of vascular malformations of the mandible: a description of 12 cases

This study evaluated the treatment of intraosseous vascular malformation of the mandible. We analysed the medical records of 12 patients treated at the Salpêtrière Hospital (Paris, France) for vascular malformation of the mandible between 1965 and 1996. There were six male and six female patients, with a mean age of 16 years. The mean follow-up time was ten years. The treatment was surgery (enucleation or resection) or interventional radiology (arterial embolization or transosseous transcutaneous embolization).There are several indications for treatment, including age, and the size and type of vascular malformation (active or passive).     

TGF-beta1 induces accumulation of dendritic cells in the odontoblast layer

TGF-beta1 released from dentin degraded by bacterial or iatrogenic agents is suspected to influence dental pulp response, including the modulation of cell migration. To determine the consequences of TGF-beta1 action on pulp immune cells, we analyzed, by immunohistochemistry, the effect of transdentinally diffusing TGF-beta1 on their localization in a human tooth slice culture model. TGF-beta1 induced an accumulation of HLA-DR-positive cells in both odontoblast and subodontoblast layers of the stimulated zone. Together with HLA-DR, these cells co-expressed Factor XIIIa and CD68, two features of immature antigen-presenting dendritic cells (DC), as well as the TGF-beta1 specific receptor TbetaRII. In contrast, no effect could be detected on the localization of either mature DC-LAMP-positive DC or of T- and B-lymphocytes. Analysis of these data suggests that TGF-beta1 released from dentin degraded by bacterial or iatrogenic agents could be involved in the immune response of the dental pulp resulting from tooth injury.