A multicenter phase II randomized trial of gemcitabine followed by erlotinib at progression, versus the reverse sequence, in vulnerable elderly patients with advanced non small-cell lung cancer selected with a comprehensive geriatric assessment (the GFPC 0505 study).

BACKGROUND: The aim of this randomized phase II trial was to evaluate the feasibility and activity of weekly gemcitabine (G) followed by erlotinib at disease progression (arm A) versus erlotinib followed by G at progression (arm B) in vulnerable elderly patients with advanced non small-cell lung cancer (NSCLC), selected on the basis of a comprehensive geriatric assessment (CGA). METHODS: Vulnerable elderly chemotherapy-naive patients with stage IIIB/IV NSCLC were selected after a CGA (socioeconomic, cognitive and emotional status, depression, nutritional status, ADL and IADL assessments). The primary endpoint was the time to second progression (TTP2). Overall survival (OS), time to first progression (TTP1) and safety were secondary endpoints. RESULTS: Between May 2006 and January 2010, 21 centers enrolled 100 patients, of whom 94 were eligible. TTP2 was 4.3 and 3.5 months in arm A and arm B, respectively; TTP1 was 2.5 and 2.2 months; and the median OS time was 4.4 and 3.9 months. The respective one-year survival rates were 27.3% and 20%. There was no major unexpected toxicity. CONCLUSION: In vulnerable elderly patients with NSCLC not selected for EGFR expression, both strategies were feasible but had modest efficacy. Further studies are needed to identify elderly patients who should receive palliative care only.

A multicentre phase II randomised trial of weekly docetaxel/gemcitabine followed by erlotinib on progression, vs the reverse sequence, in elderly patients with advanced non small-cell lung cancer selected with a comprehensive geriatric assessment (the GFPC 0504 study).

BACKGROUND: Elderly cancer patients form a heterogeneous population in which therapeutic decision-making is often difficult. The aim of this randomised phase II trial was to evaluate the feasibility and activity of weekly docetaxel/gemcitabine (DG) followed by erlotinib after progression (arm A) vs erlotinib followed by DG after progression (arm B) in fit elderly patients with advanced non small-cell lung cancer (NSCLC). METHODS: Elderly chemotherapy-naive patients with stage IIIB/IV NSCLC were selected after a comprehensive geriatric assessment (socioeconomic, cognitive, depression, ADL and IADL assessments). The primary endpoint was the time to second progression (TTP2). Overall survival (OS), the time to first progression (TTP1) and safety were secondary endpoints. RESULTS: Between July 2006 and November 2008, 22 centres enrolled 100 patients. TTP2 was 7.5 and 5.8 months in arm A and arm B, respectively; TTP1 was 4.7 and 2.7 months; and the median OS time was 9.4 and 7.1 months; the respective 1-year survival rates were 36.2 and 31.4%. There was no major unexpected toxicity. CONCLUSION: These results suggest that weekly DG, followed by erlotinib, is a promising treatment for fit elderly patients with NSCLC; the efficacy of the reverse sequence was insufficient to recommend it for EGFR-non-selected patients.

[Comprehensive geriatric assessment and complications after resection for lung cancer]. / Evaluation gériatrique et morbidité après exérèse pulmonaire pour cancer bronchique.

BACKGROUND: With the expanding elderly population comes an increasing prevalence of lung cancer. Surgery remains the mainstay of treatment for early-stage non-small cell lung cancer. Standard treatment strategies have mostly been validated in young adults. Curative resection is feasible in older patients but careful preoperative evaluation is needed, taking into account the physiologic changes that occur with ageing. A tool used by geriatricians, a comprehensive geriatric assessment, can contribute to our understanding of physiologic age through an evaluation of prognostic factors that are independent predictors of morbidity. PATIENTS: Study 08-05 of the French Lung Oncology Group is a prospective, national, multicentre study. All patients aged over 70 years with a suspicion of lung cancer, receiving curative lung resection, will be included. After inclusion, a comprehensive geriatric assessment (evaluating such diverse areas as functional status, nutritional status, cognition, psychological functioning, and social support) will be performed. The primary outcome is the value of the comprehensive geriatric assessment in predicting the risk of post-operative complications after lung resection for cancer. Post-operative morbidity at 30-days after pulmonary resection will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. The follow-up period is one year. EXPECTED RESULTS: This global assessment may help to initiate specific care plans for the management of lung cancer in the elderly.

An open multicenter phase II trial of docetaxel-gemcitabine in Charlson score and performance status (PS) selected elderly patients with stage IIIB pleura/IV non-small-cell lung cancer (NSCLC): the GFPC 02-02a study.

UNLABELLED: The aim of this study was to determine the impact of patient selection based on age, comorbidity and performance status on the efficacy of platinum-free combination therapy on non-small-cell lung cancer after 65 years of age. We analyzed the overall response rate, the median survival time, the 1-year survival rate, toxicity and quality of life after one to three 6-week cycles of docetaxel 30mg/m(2) weekly and gemcitabine 900mg/m(2) at weeks 1, 2, 4 and 5. Fifty patients (median age 73.7 years) were eligible. The mean number of comorbid conditions per patient was 0.8 [Balducci L. Lung cancer and aging. ASCO 2005. Educational book. p. 587-91; Piquet J, Blanchon F, Grivaux M, et al. Primary bronchial carcinoma in elderly subjects in France. Rev Mal Respir 2003;20:691-9; Jatoi A, Hillman S, Stella P, et al. Should elderly non-small-cell lung cancer patients be offered elderly-specific trials? Results of a pooled analysis from the North Central Cancer Treatment Group. J Clin Oncol 2005;23:9113-9; Balducci L, Extermann M. Management of cancer in the older person: a practical approach. Oncologist 2000;5:224-37]. Forty-five patients were assessable: 17 (34%) had an objective response, 18 (36%) had stable disease and 10 progressed (20%). The median survival time was 7 months and the 1-year survival rate 23.5%. The main grade III-IV adverse event was neutropenia (32% of patients). CONCLUSION: Platinum-free dual-agent chemotherapy gives similar results in patients over 65, selected on the basis of their precise age and comorbidity, to that reported in younger subjects.

Visits to the emergency room for asthma attacks and short-term variations in air pollution. A case-crossover study.

BACKGROUND: The 'case-crossover' design is a strategy fitted to studying transient effects of intermittent exposure on acute-onset disease occurring shortly after exposure. It has the important advantage of eliminating most confounding variables, allowing a stronger causality inference. OBJECTIVES: The objective of the study was to evaluate the relationships between emergency room (ER) visits for asthma attacks and gaseous air pollution changes. METHODS: The study included 549 individuals, 3-49 years old, visiting the ER during 1 year. Exposure to gaseous air pollutants (SO2, NO2, O3) on the same day and up to 4 days before was computed according to the patient's address. The statistical analysis included meteorological data as potential confounding variables. RESULTS: No association could be shown between ER visits and SO2 or NO2 levels. In contrast, there was a statistically significant association between ER visits and mean O3 levels, on the day of admission and also on D -2 and D -3. For an increase of 10 microg/m3, the risk of requiring an ER admission increased by 6-10%. CONCLUSIONS: Using this new strategy, we confirmed that ozone changes lead to a moderate increase in risk of requiring an ER admission in asthmatic subjects.

Rhinitis alone or rhinitis plus asthma: what makes the difference?

This paper examines the clinical expression of asthma in a group of patients displaying rhinitis according to age, sex, associated symptoms, smoking, familial history of asthma, atopy, type of sensitization to aeroallergens (pollens and/or indoor allergens), total serum immunoglobulin E (IgE), and blood eosinophils. A total of 117 adults with rhinitis were analysed on the basis of symptoms. Among them, 51 also displayed asthma, defined as a history of recurrent episodes of dyspnoea with a reversible airflow obstruction or a positive methacholine challenge. The logistic regression analysis carried out in a stepwise approach, combining several factors, showed that various parameters affected the risk of having asthma associated with rhinitis. A further analysis was made in 74 rhinitis patients comparing 42 subjects without nonallergic airway hyperresponsiveness (NAAH) to 32 patients with asthma and NAAH. Atopy, high total serum IgE levels, elevated blood eosinophil count and maternal asthma were associated with asthma. Furthermore, in atopic patients, pollen sensitization was more closely related to rhinitis alone, whereas sensitization to indoor allergens was a major determinant for the association of asthma with the symptoms of rhinitis. The same risk factors as those found in the clinical part of the study discriminated the patients with rhinitis without NAAH from those with rhinitis, asthma and NAAH. In conclusion, this study gives new insights into the relationships between asthma and rhinitis.

[Severe bronchial stenosis with upstream bronchiectasis in an arc welder: causal relation or epiphenomenon?]. / Sténose bronchique serrée avec bronchectasies d'amont chez un soudeur à l'arc: relation causale ou épiphénomène?

This case concerns an arc welder who presented suppurative bronchiectasis and episodes of purulent left side pleurisy in relation to cystic bronchiectasis of the left lower lobe and a very severe stenosis at the origin of the main left bronchus. The medicolegal problem was to assess the causal relationship between these lesions and occupational exposure. They do not come under the heading of table 44 of the General List and we made this the aim of discretionary award in front of a regional committee of compensation for occupational disease.

[Aneurysm of the abdominal aorta and preoperative disseminated intravascular coagulation]. / Anévrysme de l'aorte abdominale et coagulation intravasculaire préopératoire.

A case of abdominal aortic aneurysm associated with preoperative signs of disseminated intravascular coagulation is reported. The 69-year-old female patient presented with spontaneously appearing petechiae and bruising. She had 0.95 g.l-1 fibrinogen, 105 G.l-1 platelets, and 100 micrograms.ml-1 fibrin and fibrinogen degradation products. Investigations revealed an 80 mm diameter aneurysm of the abdominal aorta, extending from the coeliac trunk to the iliac arteries. Heparin 7,000 IU.day-1 resulted in a biological improvement for a week only. At that time, levels of coagulation factors were: 92% factor II, 88% factor V, 100% factors VII and X, 100% antithrombin III. Surgical cure of the aneurysm was nevertheless carried out. Twenty standard units of platelets, 8 g fibrinogen, four units of fresh frozen plasma, five homologous and two autologous red cell units were transfused during the procedure. No coagulation factors were necessary during the postoperative course, which was uneventful. The management of coagulation factor infusions, before or after aortic cross-clamping, is discussed.

[Lung biopsy by thoracoscopy (author's transl)]. / La biopsie pulmonaire par thoracoscopie. Etude préliminaire.

60 patients had 1 to 7 biopsies during thoracoscopy under light anaesthesia without tracheal intubation. Biopsies were performed under direct vision using a separation puncture. Double-spoon biopsy forceps (5 mm in diameter) connected to a 120 watt diathermy apparatus avoided any air leak age and ensured haemostasis as the biopsy was taken. The dry weight of the biopsies ranged between 5 and 40 mg, allowing appropriate studies with light or electron microscope, for bacteriological and mineral analysis, and for hormone receptors search in cancer cases. A size 20 to 30 Charrière drain was left for a mean of 3 days. No serious complications arose. Ten patients had a 38 degrees C fever for a few hours. In one case early in the study a drain had to be changed on the third day. An histopathological diagnosis was made in 12 out of 14 patients with localised pulmonary opacities and in all 14 cases with diffuse opacities. In 32 cases of pleural involvement the presence or absence of concomitant lung involvement could be demonstrated. Asbestos fibres counts by electron microscopy correlated fairly with previous exposure to asbestos. The sensibility of the technique was 96% (percent of true positives) and the specificity 100% (percent of true negatives). Thoracoscopic lung biopsy may thus be compared very favourably to techniques of lung biopsy and deserves a larger studies in order to confirm its low morbidity.