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Background: The link between organizing pneumonia (OP) and gastroesophageal reflux disease (GERD) is not well known. There is little evidence in the literature to establish a causal link between GERD and OP. Objectives: The aim of the study was to assess the hypothesis that OP is more severe when it is associated with GERD and that it leads to more frequent relapses. Methods: In a retrospective study on 44 patients suffering from OP, we compared the clinical, radiological and histological characteristics of 2 groups, 1 composed of patients with GERD (n = 20) and the other of patients without GERD (n = 24). Results: The GERD group was distinguished by a higher number of patients with migratory alveolar opacities on chest radiography and thoracic computerized tomography (14/20 vs. 9/24; p = 0.03 and 18/20 vs. 13/24; p = 0.01), greater hypoxemia [60 (42-80) vs. 70 (51-112) mm Hg; p = 0.03], greater bronchoalveolar lavage cellularity [0.255 (0.1-1.8) vs. 0.150 (0.05-0.4) g/l; p = 0.035] and more frequent relapses (14/20 vs. 9/24; p = 0.03). Conclusions: OP associated with GERD is more severe and results in more frequent relapses. Microinhalation of gastric secretions might induce lung inflammation leading to OP and relapse. We suggest that typical symptoms of GERD such as pyrosis should be investigated in OP.

The aim of this study was to evaluate on 1 day the prevalence of malnutrition in different types of cancer and the use of nutrition support in patients with cancer.A 1-day prevalence survey was carried out in 154 French hospital wards. Malnutrition was defined as a body mass index (BMI)18.5 in patients75 years old or21 in patients ≥75 years old and/or body weight loss10% since disease onset. Oral food intake was measured using a visual analog scale.Nutrition status was collected for 1903 patients (1109 men and 794 women, 59.3 ± 13.2 years). Cancer was local in 25%, regional in 31%, and metastatic in 44% of patients. Performance status was 0 or 1 in 49.8%, 2 in 23.7%, 3 or 4 in 19.6% and not available in 6.5% of patients. Overall, 39% of patients were malnourished. The prevalence of malnutrition by disease site was as follows: head and neck, 48.9%; leukemia/lymphoma, 34.0%; lung, 45.3%; colon/rectum, 39.3%; esophagus and/or stomach, 60.2%; pancreas, 66.7%; breast, 20.5%; ovaries/uterus, 44.8%; and prostate, 13.9%. Regional cancer (odds ratio, 1.96; 95% confidence interval, 1.42-2.70), metastatic cancer (2.97; 2.14-4.12), previous chemotherapy (1.41; 1.05-1.89), and previous radiotherapy (1.53; 1.21-1.92) were associated with malnutrition. Only 28.4% of non-malnourished patients and 57.6% of malnourished patients received nutrition support. In all, 55% of patients stated that they were eating less than before the cancer, while 41.4% of patients stated that they had received nutrition counseling.The prevalence of malnutrition is high in patients with cancer, and systematic screening for and treatment of malnutrition is necessary.

Lung cancer is the leading cause of cancer-related deaths in industrialized countries and non small cell lung cancer (NSCLC) accounts for 85% of all lung cancers. Cisplatin doublet based chemotherapy, which is the recommended regimen in first line therapy in advanced or metastatic NSCLC, improves survival but in low proportion. Monoclonal antibodies (mAbs) are a novel promising therapeutic class used with great results in inflammatory diseases such as rheumatoid arthritis. Antibodies are natural proteins with modular structure, specific pharmacodynamics and pharmacokinetics and possibly produced against any antigens, thus giving them several advantages over small drug therapeutics. In solid tumors, therapeutic mAbs improved progression free survival (PFS) and overall survival (OS) of patients with breast and colon cancers and had considerably changed the treatment in clinical practice. In NSCLC, bevacizumab, an anti-VEGF mAb, and cetuximab, an anti-EGFR mAb, are the most studied antibodies. Bevacizumab acts on angiognenesis and improved PFS of non squamous NSCLC but in low proportion as shown in two large phase III trials. It was approved by European Medicines Agency (EMEA) and Food and Drug administration (FDA) as a first line therapy in combination with cisplatin doublet chemotherapy. Cetuximab slightly enhanced OS but did not improve PFS in two large phase III trials. These results added to high adverse effect lead to cetuximab refusal by EMEA and FDA in NSCLC. At first glance, the results of mAbs in NSCLC are somewhat disappointing, in contrast to the benefits obtained with mAb treatments in other solid tumors. However, many other mAbs directed against novel targets, such as IGF1-R or CTLA-4, and new mAbs targeting VEGFR and EGFR pathways with different pharmacodymamical and pharmacokinetic properties are under evaluation and may change our vision of taking care of patients with NSCLC. In conclusion, it seems that mAbs therapy in NSCLC clearly marks the start of a new era in NSCLC treatment, with promises in improving patient survival and quality of life.

Introduction Vinflunine (Javlor) has shown significant antitumour activity in advanced non-small cell lung cancer (NSCLC). We propose to define the recommended dose of vinflunine in combination with gemcitabine for treatment of advanced NSCLC in chemonaive patients. Methods A phase I and pharmacokinetic study was conducted to determine the maximum tolerated dose and to establish the recommended dose of vinflunine (VFL) administered on day 1 every 21 days combined with gemcitabine given on days 1 and 8 every 3 weeks. Results Nineteen patients were included in this study. Three patients experienced a dose limiting toxicity, with constipation in one patient, hypertension in one patient, and constipation and febrile neutropenia in one patient. The combination of VFL 320 mg/m 2 and gemcitabine 1250 mg/m 2 was defined as the maximum tolerated dose. The recommended dose was established at the dose of VFL 320 mg/m 2 combined with gemcitabine 1000 mg/m 2 . Neither VFL nor gemcitabine seemed to be influencing the pharmacokinetics of each other. All patients were evaluable for tumor response. Seven presented a partial response and eight experienced a stable disease. Conclusions The combination of VFL 320 mg/m 2 administered on day 1 combined with gemcitabine 1000 mg/m 2 given on days 1 and 8 every 3 weeks is established as the RD and was shown to be active in these chemonaive NSCLC patients.

Background This multicenter, randomized, phase III study compared the efficacy, including progression-free survival (PFS), and safety of gemcitabine–docetaxel (GD) combination versus cisplatin–vinorelbine (CV) in the treatment of advanced non-small-cell lung cancer (NSCLC). Patients and methods Chemonaive patients with stage IIIB or IV NSCLC were treated with GD (gemcitabine 1000 mg/m2 days 1 and 8 plus docetaxel 85 mg/m2 day 8, every 3 weeks for eight cycles) or CV (cisplatin 100 mg/m2 day 1 plus vinorelbine 30 mg/m2, days 1, 8, 15 and 22, every 4 weeks for six cycles). Results A total of 311 patients were enrolled (155 GD and 156 CV). Neither PFS nor overall survival differed significantly between the two arms (median PFS 4.2 and 4 months; median survival 11.1 and 9.6 months; 1-year survival 46% and 42%, for GD and CV, respectively). For the GD arm compared with the CV arm, the hazard ratio for PFS was 1.04 [95% confidence interval (CI) 0.83–1.32], and for overall survival, it was 0.90 (95% CI 0.70–1.16). Objective response rates did not differ significantly (31% for GD, 35.9% for CV). Myelosupression, emesis and frequency of febrile neutropenia were less pronounced on the GD arm, whereas fluid retention and pulmonary events were more pronounced. The CV arm experienced a higher number of serious adverse events and a lower compliance with the protocol. There was no quality of life (QoL) difference between arms. Median time to definite impairment of health-related QoL was 153 and 168 days in GD and CV arms, respectively. Conclusions There was no advantage in PFS with GD compared with CV; however, the CV regimen had higher rate of toxic events, mainly myelosuppression. The herein, non-platinum-containing regimen could be considered as a rational alternative to the cisplatin-based doublet.

Background The survival benefit associated with first-line chemotherapy in advanced lung cancer led to the need for second-line chemotherapy. Docetaxel (Taxotere®) has proven efficacy in both settings. This study evaluated the safety and efficacy of two doses of docetaxel in patients with non-small-cell lung cancer who had failed first-line platinum-based chemotherapy. Patients and methods In total, 182 patients from 24 French centres were randomised and treated with either docetaxel 75 mg/m2 (arm A) or 100 mg/m2 (arm B) every 3 weeks. Baseline characteristics were well balanced, except more patients in arm A had metastatic disease (91.4% versus 78.7%) and therefore the median number of sites involved for arm A was three compared with two for arm B. Results Median time to treatment failure was 1.34 months [95% confidence interval (CI) 1.28–1.64] for arm A and 1.64 months (95% CI 1.34–2.62) for arm B. Median overall survival was 4.7 months (95% CI 3.8–5.9) for arm A versus 6.7 months (95% CI 4.8–7.1) for arm B. According to a blinded expert panel, disease control was achieved in 35 (43.8%) patients in arm A and 39 (49.4%) patients in arm B. More patients in arm B experienced grade 3–4 neutropenia (B: 72.7% versus A: 44.0%), asthenia (B: 20.2% versus A: 10.8%) and infection (B: 6.7% versus A: 2.2%). Three treatment-related deaths were reported in each arm. Conclusions The optimal docetaxel dosage in this second-line setting is 75 mg/m2, as it has a more favourable safety profile and on balance a similar efficacy to the 100 mg/m2 dose.

Aims: A case–control study was carried out between 1998 and 2000 to investigate the relation between systemic sclerosis and occupational exposure. Methods: Eighty cases of systemic sclerosis admitted consecutively to the Department of Internal Medicine at the University Hospital of Tours from 1998 to 2000 were included. For each case, two age, gender, and smoking habits matched controls hospitalised during the same period in the same department were selected. A committee of experts was set up retrospectively to assess occupational exposure. Exposure to silica dust and organic solvents (such as trichlorethylene and other chlorinated solvents, and benzene and other aromatic solvents) was investigated using semiquantitative estimates of exposure. An exposure score was calculated for each subject based on probability, intensity, daily frequency, and duration of exposure for each period of employment. The final cumulative exposure score was obtained, taking into account all periods of employment. Results: Significant associations with SS were observed for crystalline silica, trichlorethylene, chlorinated solvents, toluene, aromatic solvents, ketones, white spirit, epoxy resins, and welding fumes. Risk of SS was significantly associated with a high final cumulative exposure score of occupational exposure to crystalline silica, trichlorethylene, chlorinated solvents, welding fumes, and any types of solvents. Conclusion: Results confirm the influence of occupational risk factors in the occurrence of SS in both men and women. The link is not only with silica but also with other compounds such as solvents.

A randomized phase II trial of oral vs. intravenous (i.v.) vinorelbine was designed to determine the efficacy and safety of oral vinorelbine with an intrapatient dose escalation in previously untreated patients with advanced non-small-cell lung cancer (NSCLC).Between December 1997 and April 1999, 115 patients with stage IIIB or IV NSCLC were randomized (2 to 1) to receive either oral vinorelbine at a dose of 60 mg/m2/week for the first three administrations and then increased to 80 mg/m2/week in the absence of severe neutropenia, or i.v. vinorelbine at 30 mg/m2/week.One hundred and fourteen patients (76 in the oral arm and 38 in the i.v. arm) were treated. Ninety-eight patients (86%) were eligible and assessable. The two treatment arms were well-balanced for demographic and prognostic features. After external panel review, the response rates in evaluable patients were 14%, in the oral arm and 12% in the i.v. arm. The median progression-free survival with oral and i.v. vinorelbine was 3.2 months and 2.1 months, respectively, and the median survival 9.3 and 7.9 months, respectively. The most common hematological toxicity was neutropenia, which was severe (grade 3-4) in 46% of patients and for 7% of administrations in the oral arm, and in 62% of patients and for 25% of administrations in the i.v. arm. Non-hematological toxicities including nausea, vomiting, anorexia, weight loss, diarrhea .and constipation were generally mild to moderate.The activity of oral and i.v. vinorelbine in advanced NSCLC appears to be comparable. The safety profiles of both formulations look qualitatively similar. Oral vinorelbine can therefore be considered a good alternative to i.v. administration.

Using nebulization to deliver aminoglycosides may be of benefit in cystic fibrosis (CF) patients colonized byPseudomonas aeruginosa. However, one problem with this route is the absence of clinical parameters allowing estimation of the mass of drug deposited in the lungs (MDL). The aim of this study was to assess whether aminoglycoside excretion in the urine reflects the MDL.Fourteen studies were performed in seven CF patients. Amikacin was mixed with albumin labelled with99mTc and nebulized with an ultrasonic nebulizer. The MDL was determined by the mass-balance technique. Urine was collected during the 24 h following inhalation and was assayed for amikacin by fluorescence polorization immunoassay (FPIA).The mean±sem MDL was 14.0±2.2% of the nebulizer charge. The mean±sem amount of amikacin excreted in the urine was 20.9±4.5 mg and correlated with the MDL (r=0.93; p=0.0001). There was, however, wide intersubject variability in both deposition and excretion in the urine.Monitoring excretion of aminoglycosides in the urine allows noninvasive estimation of the mass of drug deposited in the lung in cystic fibrosis patients, which might be useful to assess the dose-response relationship in groups of patients, but intersubject variability prevents its use for individual follow-up.

Background: The combination of etoposide plus cisplatin (EP) is considered to be standard therapy for small-cell lung cancer (SCLC). To determine whether drug intensification improves survival of patients with extensive SCLC, we compared this treatment with a four-drug regimen containing EP plus cyclophosphamide and 4'-epidoxorubicin (PCDE). Methods: In a phase III clinical trial organized by the French Federation of Cancer Institutes, patients were randomly assigned to receive either EP (n = 109; etoposide at a dose of 100 mg/m 2 on days 1-3 plus cisplatin at 100 mg/m 2 on day 2) or PCDE (n = 117; etoposide and cisplatin given as in EP plus cyclophosphamide at 400 mg/m 2 on days 1-3 and 4'-epidoxorubicin at 40 mg/m 2 on day 1) every 4 weeks. Both groups received a total of six cycles. Survival differences were analyzed by Wilcoxon and log-rank tests. Associations of treatment group and putative prognostic variables with survival were tested in the Cox proportional hazards model. Quality of life was assessed from the responses to the European Organization for Research and Treatment of Cancer quality-of-life questionnaire (C30, health status and lung cancer module 13). All statistical tests were two-sided. Results: Patients in the PCDE arm had a statistically significant higher frequency of combined complete plus partial responses compared with those in the EP arm (21% plus 55% versus 13% plus 48%, respectively; P = .02 for difference in combined objective responses). Patients in the PCDE arm survived longer than those in the EP arm (1-year survival rate: 40% and 29%, respectively; median survival: 10.5 and 9.3 months, respectively; log-rank P = .0067). In the Cox model, the relative risk of death for patients in the PCDE arm compared with those in the EP arm was 0.70 (95% confidence interval = 0.51 to 0.95); the disease also progressed more slowly in patients in the PCDE arm. Hematologic toxicity was higher in the PCDE arm (22% with documented infections compared with 8% in the EP arm; P = .0038), and the toxicity-related death rate was 9% in the PCDE arm versus 5.5% in the EP arm (P = .22). The global health status showed similar improvement in both arms during treatment. Conclusion: Compared with the EP regimen, the PCDE regimen yielded higher response rates and better survival rates in patients with extensive SCLC without affecting the quality of life of the patients during chemotherapy.

To determine the predictive value of abnormalities on high-resolution CT (HRCT) on pulmonary disease in systemic sclerosis.Fifty-two patients suffering from systemic sclerosis.Pulmonary disease was defined by pulmonary function test abnormalities, ie, total lung capacity (TLC)80% of predicted value and/or diffusion of carbon monoxide (DLCO)75% of predicted value, without any pulmonary event other than systemic sclerosis in the medical history. Patients were divided in two groups, group A with pulmonary disease (29 patients) and group B without pulmonary disease (23 patients). HRCT abnormalities were scored on whole lungs. A decision matrix was constructed to determine sensitivity, specificity, positive and negative predictive values, and false-positive and false-negative rates. A receiver operating characteristic curve was constructed to determine the best compromise between sensitivity and specificity.HRCT total scores were higher in group A (9.0+/-4.3) than in group B (5.0+/-2.8) (p0.001) and they correlated with TLC (r =-0.39, p0.005) and DLCO (r = -0.50, p0.0002). An HRCT score of 7 corresponded to the best compromise between sensitivity (0.60) and specificity (0.83), with a positive predictive value of 0.82. Taking into account a value of 10 for the HRCT score increased specificity to 1 but decreased sensitivity to 0.41.A minimum score of 7 would be required to consider HRCT abnormalities in systemic sclerosis as predictive of pulmonary disease. An HRCT score of 10 makes it possible to establish the diagnosis of lung involvement severe enough to impair pulmonary function.

The purpose of this study was to determine the ability of technetium-99m J001X scintigraphy to image active pulmonary involvement in patients suffering from rheumatoid arthritis (RA). J001X is a fully characterized acylated poly(1,3)galactoside, isolated from Klebsiella membranes, which is able to bind recruited macrophages after aerosol administration. J001X scintigraphy was compared with high-resolution computed tomography (HRCT), pulmonary function tests (PFTs) and bronchoalveolar lavage (BAL) in 15 patients suffering from RA. Patients were considered to have pulmonary involvement when they had an interstitial syndrome on HRCT and a decrease of 20% in TCO/VE (transfer coefficient) on PFTs and/or an abnormal BAL (lymphocytosis higher than 20% and/or percentage of neutrophils higher than 10%). Pulmonary involvement was present in eight patients, and absent in seven. Of the eight patients with pulmonary involvement, all had abnormal BAL, two had an interstitial syndrome on HRCT, two had decreased TCO/VE and three had positive J001X scintigraphy. Of the seven patients without pulmonary involvement, six had normal BAL (not available in one), two had an interstitial syndrome on HRCT, one had decreased TCO/VE and two had positive J001X scintigraphy. According to our gold standard of pulmonary involvement, the sensitivity of J001X scintigraphy for the detection of pulmonary involvement in RA was 37.5%, the specificity was 71.4% and the positive predictive value was 60%. The ability of J001X scintigraphy to detect active pulmonary involvement during RA appears unclear in this study but it may detect processes unnoticed by the other modalities. These patients will be followed 12 and 24 months later and the changes in J001X scintigraphy, HRCT and PFTs will be compared to demonstrate whether J001X scintigraphy is able to assess an active process in the pulmonary involvement during RA and to specify its predictive value.

Introduction: Although airways route is an attractive alternative route to systemic administration, increasing concentration of the drug in the lungs while reducing whole-body toxicity, it is not often exploited in lung cancer treatment. After checking that cetuximab, an anti-cancer antibody binding to EGFR, resists the physical constraints of nebulization, we established an animal model of lung tumour sensitive to the antibody. Then, we used the animal model to evaluate cetuximab antitumor efficiency, biodistribution and pharmacokinetic following delivery through airways. Methods: Cetuximab was nebulized with the IA-1C MicroSprayer™ (PennCentury Inc., USA) connected to a FMJ-250 high pressure syringe, a device used to administrate, directly inside the trachea, aerosol in mice. The effect of nebulization on cetuximab was assessed in terms of its affinity for membrane EGFR (using flow cytometry), inhibition of cell growth and inhibition of EGFR phosphorylation. To ensure that airways delivery of cetuximab did not lead to additional toxicity, we compared tolerance to cetuximab delivered through systemic and pulmonary routes in mice without tumors. An animal model of lung cancer sensitive to cetuximab was established and consists in the instillation of human epidermoid carcinoma cells endotracheally in nude mice. The model was exploited to study cetuximab biodistribution and pharmacokinetic following delivery through systemic and pulmonary routes. Therapeutic efficiency of nebulized cetuximab was determined in tumor- bearing animals. Results: Firstly, our results showed that MicroSprayer™ did not alter cetuximab integrity, immunological and pharmacological properties. Secondly, airways administration of cetuximab in mice seemed to be well-tolerated and did not induced additional toxicity in lungs, kidney, colon, skin, liver or spleen. Finally, higher, more rapid and prolonged lung uptake was observed in animals receiving cetuximab through the pulmonary route. Antitumor efficiency of nebulized cetuximab is currently under investigation. Conclusion: These results highlight the potential of the pulmonary route for delivery of anticancer antibody in lung cancer.

The purpose of this research was to evaluate the safety of pulmonary administration of gemcitabine and to determine the maximum tolerated dose by weekly pulmonary administrations in an animal model. Five groups of eight Wistar rats received gemcitabine at doses of 2, 4, 6, or 8 mg/kg or the vehicle solution by endotracheal spray with scintigraphic imaging of lung deposition. In order to document the safety of digestive exposure, five groups of eight rats received gemcitabine at the same dosages or the vehicle solution by gavage. Nine weekly sessions were planned, and blood cell counts and histological examinations were performed in live animals at day 64. Scintigraphic imaging confirmed pulmonary deposition in 310 of 316 spray administrations (98%) with homogeneous pattern of deposition. The maximum tolerated dose of gemcitabine by pulmonary administration was 4 mg/kg. At this dosage, administered once a week for 9 consecutive weeks, there were no chemotherapy-related deaths and no clinical, histological, or hematological signs of toxicity except for a decrease in platelet and red blood cell counts, with no clinical significance. The toxicity of gemcitabine was higher via oral than lung delivery in terms of weight loss and white blood cell toxicity at dosages of 2, 4, and 6 mg/kg. Pulmonary administration of gemcitabine is safe in rats at a maximum tolerated dose of 4 mg/kg once a week for 9 weeks. At an equivalent dosage, the toxicity of gemcitabine is lower by lung than oral administration.

Summary Purpose: This randomized phase II multicenter trial aimed at evaluating the efficacy and safety of the 4-week versus 3-week schedules of gemcitabine monotherapy in previously untreated elderly patients with advanced non-small cell lung cancer (NSCLC). Patients and methods: Chemonaive patients with stage IIIB or IV NSCLC, and age between 70 and 90 years, were randomized to receive gemcitabine dose of either 1000 mg/m2 on days 1, 8, 15, every 28 days (arm Q4W), or 1125 mg/m2 on days 1 and 8, every 21 days (arm Q3W). Results: From June 1999 to January 2001, 81 patients (42 on arm Q4W; 39 on arm Q3W) were included. The median age was 75 on both arms; most patients (82.7%) were male, and had a Karnofsky performance status of 80 or 90 (76.5%). For arms Q4W and Q3W, respectively, the median time to treatment failure was 83 days (95% CI, 69–98 days) versus 92 days (95% CI, 63–113), and the median survival was 154 days (95% CI, 108–227) versus 205 days (95% CI, 125–344). The objective response rate was higher on arm Q3W (28.2%) than on arm Q4W (14.3%). Total number of cycles administered was 132 on arm Q4W (median 3, range 1–10 cycles) and 169 on arm Q3W (median 4, range 1–9 cycles). Patients on arm Q4W and Q3W, respectively, received 100.1 and 99.8% of the planned weekly mean dose. The most common grade, three to four toxicities, was neutropenia (17.1% on arm Q4W versus 18.9% on arm Q3W) and thrombocytopenia (12.2% on arm Q4W versus 2.6% on arm Q3W). Conclusion: Although both 3- and 4-week gemcitabine regimens were safely and effectively administered in chemonaive elderly patients with advanced NSCLC, the 3-week schedule appears to be the more convenient for this population. Moreover, even if this is only a phase II study this 3-week schedule appears to be at least as efficient as the 4-week regimen.

Summary Background: Patient preference as well as concerns and difficulties with intravenous access and pharmaco-economic issues have driven the development of oral vinorelbine. Patients and methods: Four phase II studies were conducted in chemotherapy- naive non-small-cell lung cancer (NSCLC) and as first-line chemotherapy of advanced breast cancer (ABC). As recommended in the phase I dose-finding study, the first step used a weekly dose of 80 mg/m2. This regimen was associated with an excessive rate of early deaths (10%) due to complicated neutropenia and led to discontinuati on of the first two studies. In a second step, the dose of 60 mg/m2/week was given for the first three courses and subsequently increased to 80 mg/m2/week, in the absence of severe neutropenia. Results: One hundred and thirty eight patients (76 with NSCLC and 62 with ABC) received this regimen, of whom only five were unable to undergo dose escalation. The incidence of febrile neutropenia and neutropenic sepsis were low (2.9 and 3.6%, respectively). Although severe events were uncommon, nausea/vomiting and diarrhoea were frequent and primary prophylaxis with antiemetics should be recommended. Conclusions: Overall, the safety profile of oral vinorelbine at 60 mg/m"/week for the first three courses with escalation to 80 mg/m2 is qualitatively comparable to that of i.v. vinorelbine at standard doses. Similarly to i.v. chemotherapy, close haematological monitoring is necessary. Background Vinorelbine is a semi-synthetic vinca-alkaloid which has demonstrated broad clinical antitumour activity in a weekly intravenous (i.v.) schedule. Intravenous vinorelbine has been established as one of the most active agents in the treatment of non-small-cell lung cancer (NSCLC) [1-3] and advanced breast cancer (ABC) [4]. The development of oral chemotherapy may allow improvement of patient comfort and reduction of the constraints and overall cost of the treatment [5, 6]. A soft gelatin capsule was formulated and shown to be stable for at least 24 months. In a phase I dose-finding study in patients with ABC, the maximum tolerated dose was 100 mg/m2 on a weekly schedule, and the recommended dose for further clinical investigations was 80 mg/m 2 [7], Dose-limiting toxicities included neutropenia, nausea/vomiting and constipation. Preliminary evidence of activity was obtained in first and second-line treatment for ABC. An absolute bioavailability study compared an i.v. infusion of vinorelbine 25 mg/m2 with an oral administration of 80 mg/m 2 [8]. The bioavailability of the oral form was 43% ± 14. Based on the linearity of vinorelbine pharmacokinetics whatever the route of administration [9-11], it was established that the oral dose of 80 mg/m2 corresponded to an i.v. dose of 30 mg/m2 and the oral dose of 60 mg/m2 to an i.v. dose of 25 mg/m2. Interestingly, the pharmacokinetic behaviour of capsules was compared in fed and fasting conditions and was found to be similar [10]. Phase II studies were conducted in NSCLC and ABC to assess the efficacy of oral vinorelbine as a single agent. As recommended in the phase I dose-finding study, we initially studied the toxicity profile of a weekly dose of 80 mg/m2. Due to safety concerns, the study regimen had to be modified, and the starting dose of oral vinorelbine was reduced to 60 mg/m2. We will hereby report the safety profiles of oral vinorelbine in these two consecutive steps of the clinical investigation.

Performance status (PS) is universally used in oncology to evaluate the clinical condition of the patients. The performance status has been shown to correlate with survival, as well as with acute toxicity following anticancer chemotherapy [1–5]. To test whether altered performance status is associated with malnutrition, we retrospectively examined data from a 1-day malnutrition prevalence survey, carried out in 154 oncology wards of private or public hospitals in 24 cities in France [6]. Height and present and usual body weights were assessed in outpatients and inpatients who were present that day. The European Society for Clinical Nutrition and Metabolism and the Cachexia Society recently considered pre-cachectic a patient who involuntarily lost 5% of body weight during the previous 12 months [7, 8]. Malnutrition was defined as a body mass index 10% from diagnosis in our study. The prevalence of malnutrition was studied in the overall population and stratified for the performance status. Amongst 2,068 patients (1,189 men and 879 women) aged 60±13 years, nutritional status was available in 1,903 patients. The performance status was 0 in 338 (19%), 1 in 560 (32%), 2 in 451 (25%), 3 in 249 (14%), and 4 in 129 (7%) patients. Overall, 723 (38%) of the patients were malnourished. The prevalences of malnutrition were 14.4%, 31.4%, 52.3%, 53.6%, and 65.3% in patients with a performance status ranging from 0 to 4, respectively (Fig. 1). In comparison to patients with performance status 0, the relative risk of malnutrition was 2.5 (p

Summary Background Although the average age of lung cancer patients is increasing, many elderly patients remain undertreated, mainly because of the fear of higher treatment toxicity in this category of patients. We conducted a study to evaluate the efficacy and tolerability of a combination therapy with carboplatin (C) and etoposide phosphate (EP) in elderly patients with Small-Cell Lung Cancer (SCLC). Patients and methods Previously untreated patients older than 70 years with stage IIIB/IV SCLC received a combination of EP (100 mg/m2 D1, D2, D3) and C (Dl, dose calculated according to the Calvert formula). Response rate, survival and toxicity were assessed. Results Thirty-eight patients (mean age 76 years, range 70–88 years) received a total of 162 cycles. Eighteen patients (47%) received the six scheduled cycles. Thirty patients were evaluable for efficacy (2 CR and 20 PR). The median survival was 237 days and the one-year probability of survival was 26%. The most common adverse effect was transient grade 3 or 4 neutropenia, observed during 57% of evaluable cycles, while five episodes of febrile neutropenia also occurred, with one fatal (bactaeriemia). It is noteworthy that no renal or liver toxicity was observed, and no mucitis was noted. Unfortunately, a relatively high proportion of patients died shortly after the start of the study. Although most deaths seemed unrelated to the treatment, the possibility of its exacerbatory effect on comorbidities, especially cardiovascular, cannot be excluded. Conclusion The two-drug regimen of carboplatin and etoposide phosphate is feasible in most elderly patients with an acceptable toxicity, and the overall results suggest that patients even older than 70 years may benefit from full treatment. Therefore, consideration should be given to offering active treatment to most patients with SCLC, regardless of age but with special attention paid to comorbidities.

A phase II study was conducted to determine the efficacy and the safety of docetaxel combined with vinorelbine as first-line chemotherapy in patients with metastatic or unresectable non-small cell lung cancer (NSCLC). 39 patients, median age 54 years (range: 35–69), with stage IIIB (5 patients; 13%) or IV (34 patients; 87%) NSCLC were treated with 75 mg/m2 docetaxel given intravenously (i.v.) over 1 h on day 1 and with 20 mg/m2 vinorelbine given i.v. over 15 to 30 min on days 1 and 5. Cycles were repeated every 3 weeks. 9 of the 39 patients had a partial response (overall response rate 23.1%, 95% confidence interval (CI): 11.1–39.3%) with a median duration of response of 20 weeks (95% CI; 17–30). The median survival was 40 weeks (95% CI: 21–49 weeks) with a 1-year survival rate of 31% in the intent-to-treat population. Neutropenia grade IV occurred in 33 patients (92%). 16 patients (41%) experienced febrile neutropenia with a concomitant stomatitis in 9 patients (23%). One patient died due to febrile neutropenia associated with a grade 4 stomatitis and 1 patient due to a septicaemia concomitant with a grade 4 neutropenia. Although the combination of docetaxel and vinorelbine is feasible, the efficacy does not seem to be improved compared with single-agent docetaxel or vinorelbine and the rate of febrile neutropenia is unacceptable in this population with incurable disease. Therefore, different doses and/or schedules are to be explored.

Adjuvant treatments of non-small cell lung cancer (radiotherapy and chemotherapy) before or after surgery, have been tested in numerous trials, more particularly as regards postoperative chemotherapy. For a long time the results were disappointing, and in randomized studies none of the therapeutic regimens prescribed could improve the patient’s survival. New hopes of advances in this matter were raised by Goldie and Coldman [1] whose mathematical concept recommended a systemic treatment applied as early as possible in cases with localized tumour. The advent of Platinum [2], the results obtained in metastatic tumours by some associations with Platinum and those obtained in localized tumours by chemotherapy-radiotherapy [3] have been promising. Many phase II studies have shown that surgery was feasible after 2 or 3 cycles of chemotherapy [4, 8] even thought 1 of them [9] had observed a high rate of progression after chemotherapy which prevented surgery.

In a randomized, multicenter, open-label study, 490 ambulatory adult patients with lower respiratory tract infection (LRTI) were randomized to roxithromycin (ROX) 150 mg b.i.d. orally (n = 244) or amoxicillin plus clavulanic acid (AMX + CA) as 500 mg AMX + 125 mg CA t.i.d orally (n = 24). Clinical results were analyzed in 477 patients with acute bronchitis (79%), chronic bronchitis (CB) (14%), and pneumonia (7%). There were significantly more patients with underlying disease (cardiovascular diseases, p = 0.045; and alcoholism, (p less than 0.001), and more patients over the age of 65 years (p = 0.045) in the ROX group. Overall clinical efficacy was similar in both groups: 88% (206:235) in the ROX group and 85% (205:242) in the AMX + CA group. Side effects were reported in 67 cases (28%) in the AMX + CA group and in 21 cases (9%) in the ROX group (p less than 0.0001), causing withdrawal in 21 and three cases, respectively (p less than 0.001). Thus, despite being administered to a significantly older and more ill group of patients with LRTI, roxithromycin was as effective as amoxicillin plus clavulanic acid and better tolerated.

Introduction et but de l’etude L’etude Nutricancer a confirme la forte prevalence de la denutrition chez les malades porteurs d’affections neoplasiques. Le but de cette etude a ete d’evaluer quelle perception des malades avaient sur leur etat nutritionnel, leur appetit et la prise en charge nutritionnelle qui leur etait proposee. Materiel et methods Dans le cadre de l’etude Nutricancer, une evaluation de l’etat nutritionnel a ete realisee un jour donne chez tous les malades presentant un cancer vus dans 154 unites de 86 services dans 24 villes en France (n=2068, 1 189 hommes et 879 femmes, âge moyen : 60±13 ans). Parallelement, un auto-questionnaire concernant la perte de poids depuis le debut de la maladie et au cours du dernier mois, l’appreciation subjective de la prise alimentaire depuis le debut de la maladie et le niveau des ingesta le jour de l’etude [echelle visuelle analogique (EVA) de 0 (pas d’ingesta) a 10 (ingesta normaux)] et la prise en charge nutritionnelle proposee, a ete distribue aux malades. Resultats 1 074 auto-questionnaires ont ete analyses. Les malades etaient hospitalises en hematologie (17,8 %), medecine (6 %), oncologie (45,9 %), pneumologie (11,8 %), ORL (17,1 %) ou autres (1,4 %). 653 malades (60,8 %) affirmaient avoir perdu du poids depuis le debut de leur maladie. 11,9% avaient perdu moins de 2,5 kg, 24 % entre 3 et 5 kg, 34,8 % entre 6 et 10 kg, 15,2 % entre 11 et 15 kg et 14,1 % plus de 16 kg 464 malades estimaient avoir perdu du poids au cours du dernier mois (moyenne 2,5 kg). 55 % des malades avaient l’impression de s’alimenter moins qu’avant la maladie. 15,7 % des malades avaient une EVA entre 0 et 3, 27,3 % entre 3 et 6, 27,5 % entre 6 et 9 et 29,5 % a 10. Les cinq premieres causes de diminution de la prise alimentaire etaient : une anorexie (62,5 %), une perte du gout (42,2 % dont 23,6 % pour le sale et 19,8 % pour le sucre), des nausees (29,9 %), des troubles de la deglutition (25,6 %) et une alimentation mauvaise ou inadaptee (18,9 %). 41,4 % des personnes interrogees disaient avoir recu des conseils nutritionnels. Ces conseils avaient ete prodigues par le medecin traitant (12,9 %), des medecins hospitaliers (31,9 %), un medecin nutritionniste (10,4 %), un dieteticien (56,3 %) ou une autre personne (10,2 %). 36,9 % des malades ont recu des complements nutritionnels oraux. Conclusions Ce travail confirme que la denutrition est un probleme majeur chez les malades porteurs d’un cancer. Comparativement a la perte de poids et aux difficultes alimentaires alleguees par les malades, la prise en charge nutritionnelle semble encore insuffisante. L’anorexie et la perte de gout qui sont les causes principales de la reduction des apports alimentaires, devraient susciter une recherche specifique.

9126 Background: The evaluation of the performance status (PS) is universally used in oncology and a PS of 2 is known as associated with reduced survival and increased risk of toxicity following chemotherapy. The aim of the present study was to evaluate the prevalence of malnutrition in a non selected population of cancer patients (pts) and how malnutrition correlates with poor PS. Methods: A prospective one-day prevalence survey was carried out in 154 wards of private or public hospitals in 24 cities in France. Height, present and usual body weight were assessed in outpatients and inpatients who were present that day. Malnutrition was defined as a Body Mass Index 10% from the beginning of the disease. The prevalence of malnutrition was studied in the overall population and stratified for the type of cancer and the PS. Results: 2,068 pts (1,189 men and 879 women) aged 60±13 yrs were evaluated and nutritional status was available in 1,903 pts. The PS was 0 or 1 in 52.3% of pts, 2 in 25.3%, 3 or 4 in 22.4%. Overall, 38% of pts were malnourished. Prevalence of malnutrition according to the primary tumor was: pancreas (n=42): 67%, oesophagus (n=41): 61%, stomach (n=41): 59%, head and neck (n=366): 49%, lung (n=247): 45%, ovary/uterus (n=87): 45%, colon/rectum (n=191): 39%, leukemia/lymphoma (n=377): 34%, breast (n=229): 21%, prostate (n=72): 14%. The prevalence of malnutrition was 14.4%, 31.4%, 52.3%, 53.6%, and 65.3% in pts with a PS ranging from 0 to 4, respectively. In comparison to PS-0 pts, Relative risk (RR) of malnutrition was 2.5 (p < 0.0001) in PS-1 pts and 6.4 in PS-2 pts (p50% of PS-2 pts. Systematic screening and care of malnutrition is mandatory to improve the PS and subsequently treatment tolerability in these pts. No significant financial relationships to disclose.

7016 Background: Since local failure remains frequent after RT in these patients (pts), a randomized trial was designed to assess the efficacy of concurrent daily RT-Cb given after induction chemotherapy (ICT) on local control. Method: Unresectable stage III NSCLC pts (any weight loss, WHO PS 0–2, ± supraclavicular lymph node or superior vena cava syndrom) were eligible. ICT (Vr 30 mg/m2, week (w) 1, 3, 5, and 15 mg/m2, w 2, 4, 6; P 120 mg/m2 w 1 and 5) was modified (Vr 30 mg/m2 w 1 to 9; P 100 mg/m2 w 1, 5 and 9) after 1st interim analysis (190 pts accrued) due to high incidence of metastases. CR, PR, SD pts after ICT were given RT (66 Gy, 33 fractions) with (arm B) or without (arm A) daily Cb (15 mg/m2) according to randomization performed at entry (stratification on gender, PS, histology and center). Evaluation using CT scan was performed 1 month (m) after RT, every 3 m for 3 yrs, every 6 m thereafter. To demonstrate a 10% improvement on the 1-yr local control rate, 585 pts were needed (2 interim and 1...

7266 Background: VFL (Javlor) is a novel semi-synthetic vinca-alkaloid that has shown higher in vivo antitumour activity than vinorelbine in several human tumour models. In NSCLC, non-platinum doub...