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Background: Computed tomography angiography (CTA) is used to plan TAVI procedures. We investigated the performance of pre-TAVI CTA for excluding coronary artery disease (CAD)., Methods: In total 127 patients were included. CTA images were analyzed for the presence of ≥ 50% (significant CAD) and ≥ 70% (severe CAD) diameter stenoses in proximal coronary arteries. Results were compared with invasive coronary angiography (ICA) at vessel and patient levels. Primary endpoint was the negative predictive value (NPV) of CTA for the presence of CAD., Results: A total of 342 vessels were analyzable. NPV of CTA was 97.5% for significant CAD and 96.3% for severe CAD. Positive predictive value and accuracy were 44.8% and 87.1% for significant CAD and 56.3% and 94.4% for severe CAD. At patient level, NPV for significant CAD was 88.6%., Conclusion: Pre-TAVI CTA shows good performance for ruling out CAD and could be used as a gatekeeper for ICA in selected patients., (© 2021. The Author(s).)

Hypothesis: There will be a detectable increase in overall survival (OS) using preoperative (PRE) as opposed to perioperative (PERI) chemotherapy in resectable StageI-II non-small-cell lung cancer (NSCLC)., Methods: This multicenter, open-label, randomised trial with a 2×2 factorial design first compared two chemotherapy strategies (PRE versus PERI), then two chemotherapy regimens (gemcitabine-cisplatin [GP] versus paclitaxel-carboplatin [TC]). The PRE group received two preoperative cycles followed by two additional preoperative cycles, while the PERI group underwent two preoperative cycles followed by two postoperative cycles, the 3rd and 4th cycles being given only to responders in both cases., Results: A total of 528 patients were randomised, 267 of which were assigned to the PRE group and 261 to the PERI group. Three-year OS did not differ between the two groups (67.4% and 67.7%, respectively; hazard ratio (HR)=1.01 [0.79-1.30], p=0.92), nor did 3-year disease-free survival, response rates, toxicity, or postoperative mortality. Pathological complete response was observed in 22 (8.2%) and 16 patients (6.1%), respectively. Although quality of life did not differ significantly, chemotherapy compliance was significantly higher in the PRE group. The proportion of responders who received Cycles 3 and 4 was significantly higher in the PRE group (90.4% versus 75.2%, p=0.001). In responders, the dose intensity of Cycles 3 and 4 was higher in the PRE group than in the PERI group (mean relative dose intensity of 90.4% versus 82.6%, respectively; p=0.0007). There was no difference between GP and TC in 3-year OS (HR=0.97 [95% confidence interval (CI): 0.76-1.25], p=0.80) or response rates. However, the regimens' toxicity profiles differed., Conclusions: This study failed to demonstrate any difference in survival between patients receiving preoperative and perioperative chemotherapy in early-stage NSCLC. The increase from two to four preoperative chemotherapy cycles did not increase the pathological response rate., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Introduction: Our study aimed to evaluate whether pathologic complete response (pCR) in early-stage non-small-cell lung cancer (NSCLC) after neoadjuvant chemotherapy resulted in improved outcome, and to determine predictive factors for pCR., Methods: Eligible patients with stage-IB or -II NSCLC were included in two consecutive Intergroupe Francophone de Cancérologie Thoracique phase-III trials evaluating platinum-based neoadjuvant chemotherapy, with pCR defined by the absence of viable cancer cells in the resected surgical specimen., Results: Among the 492 patients analyzed, 41 (8.3%) achieved pCR. In the pCR group, 5-year overall survival was 80.0% compared with 55.8% in the non-pCR group (p = 0.0007). In multivariate analyses, pCR was a favorable prognostic factor of overall survival (relative risk = 0.34; 95% confidence interval = 0.18-0.64) in addition to squamous-cell carcinoma, weight loss less than or equal to 5%, and stage-IB disease. Five-year disease-free survival was 80.1% in the pCR group compared to 44.8% in the non-pCR group (p < 0.0001). Two patients (4.9%) in the pCR group experienced disease recurrence compared to 193 patients (42.8%) in the non-pCR group. SCC subtype was the only independent predictor of pCR (odds ratio [OR] = 4.30; 95% confidence interval = 1.90-9.72)., Conclusion: Our results showed that pCR after preoperative chemotherapy was a favorable prognostic factor in stage-IB-II NSCLC. Our study is the largest published series evaluating pCRs after preoperative chemotherapy. The only factor predictive of pCR was squamous-cell carcinoma. Identifying molecular predictive markers for pCR may help in distinguishing patients likely to benefit from neoadjuvant chemotherapy and in choosing the most adequate preoperative chemotherapy regimen.

Background: Lung cancer in the elderly is considerably increasing in frequency, representing a public health issue. Those patients are underrepresented in clinical trials and probably not optimally treated., Methods: We performed a survey of the management and the outcome of lung cancer patients aged 70 and more in France between August 2002 and September 2003 according to age categories (70-74, 75-79 and > or =80 years). One thousand six hundred and twenty-seven patients were analysed for descriptive data and 1595 for survival., Results: Median age was 75 (70-96) and male:female ratio was 4.26 with a decrease across the age categories from 5.1 to 3.0. Tobacco-linked comorbidities were frequent. The median value of Charlson's index was 2. About 58% had a performance status (PS) 0 or 1, 30% a PS 2 and 12% a PS>2. The proportion of never-smokers (11.6%) increased significantly with age categories. Regarding imaging procedures, as much as 83.3% of the patients had at least a chest CT-scan and a brain CT-scan (or MRI) and an abdominal ultrasound or CT-scan. Best Supportive Care (BSC) as only treatment was administered to 16.1% of the patients. Among patients specifically treated, 22.9% were operated, 21.8% received mediastinal irradiation and 71.5% chemotherapy. Overall, median survival time was 9.14 months with 23.5% deaths occurring before 3 months. Low category of age, good PS, non-smoking and high body mass index (BMI) were favorable independent prognostic factors of survival. Age, PS and tobacco smoking were prognostic of early death., Conclusions: A large majority of elderly lung cancer patients in France are managed like younger counterparts regarding diagnostic procedures and treatment. Age remains an independent prognostic factor as well for overall survival as for early death., (Copyright 2010 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Background: The interest of first- and second-line treatments in non-small cell lung cancer (NSCLC) has been demonstrated by successive randomized trials. Improvements in lung cancer care have routinely allowed a significant proportion of patients to be considered for third-line treatment., Methods: A retrospective analysis was performed, including all consecutive patients with advanced NSCLC, who received at least three lines of systemic antineoplastic treatment at our institution., Results: From a population of 613 patients treated with first-line treatment, a total of 173 patients received third-line treatment (cytotoxic chemotherapy in 131 patients; epidermal growth factor (EGFR) tyrosine kinase inhibitors in 42 patients). Only 13 patients (8%) received less than 75% of the theoretical dose intensity; 22 patients (13%) presented with severe toxicities. Symptom relief and performance status (PS) improvement were observed in 121 (92% of the 131 patients with symptoms) and 90 patients (52%), respectively. Using multivariate analysis, survival after third-line treatment was significantly increased in patients younger than 70 years-old (hazard ratio [HR] = 0.73, 95% confidence interval [CI]: 0.53-0.99, p = 0.047), who smoked less than 10 pack-years (HR = 0.82, 95% CI: 0.57-0.93, p = 0.036), with no cancer-related symptoms (HR = 0.75, 95% CI: 0.61-0.92, p = 0.007), a weight loss inferior to 5 kg since the beginning of second-line (HR = 0.63, 95% CI: 0.52-0.75, p = 0.013), a PS 0 to 1 (HR = 0.81, 95% CI: 0.76-0.86, p = 0.008), and no extrathoracic tumor spread at initiation of third-line treatment (HR = 0.67, 95% CI: 0.47-0.94, p = 0.042). Disease control after both first- and second-line treatments was the strongest predictor of prolonged survival after third-line treatment (HR = 0.47, 95% CI: 0.33-0.67, p = 0.001)., Conclusions: Patients with advanced NSCLC may benefit from third-line treatment. The best candidates can be identified using standard prognostic factors, such as PS, and disease control after first- and second-line treatments.

The combination of chemotherapy and surgery is a standard of care for non-small cell lung cancer, as shown by the recently published "Standards, Options et Recommandations" (SOR) by the Fédération des Centres de Lutte contre le Cancer. This document was approved by the INCa, the SPLF, the Ligue contre le Cancer, the IFCT. However, the respective position of chemotherapy and surgery remains debated. Most trials of preoperative chemotherapy were closed when the positive studies of adjuvant chemotherapy were published. Therefore, the trials of preoperative chemotherapy lack strength to conclude on the validity of the concept. Confirmation will come from meta-analyses. Two meta-analyses based on published data have been yet published, and are positive.

This paper focuses on stage I, II and IIIA non-small cell lung cancer treatable with local treatment. It addresses five questions raised by strategies combining local treatments with chemotherapy. Even if chemotherapy increases resectability of stage III disease, the chemotherapy-surgery combination has not been demonstrated to increase survival compared to the standard chemo-radiation treatment. The results of the study by Van Meerbeeck do not support this hypothesis. Does surgery, added to chemo-radiotherapy, improve the outcome in stage IIIAN2 disease? This was the question addressed by the study by K. Albain. There is probably not clear cut answer. However, the trimodality strategy might be interesting in patients undergoing a lobectomy and might have a negative impact when a pneumonectomy has been performed. In patients with a non resectable/inoperable cancer treated with standard chemoradiation, the concomitant strategy has been shown to be superior to sequential treatment. However, due to acute toxicity, it should be delivered to selected patients, who still need to be better defined. The chemotherapy-surgery combination is becoming standard (in stage II disease) and most cooperative groups will probably stand in favour of it in 2006. The best respective timing for chemotherapy and surgery is still debated. There are many advantages in favour of preoperative chemotherapy, including better feasibility and the higher proportion of patients who can benefit. However, there is no statistically reliable demonstration of such superiority.

Introduction: Several studies have suggested that rurality is a risk factor for worse prognosis in cancer., Methods: The study population included the 2268 lung cancer cases collected between 1981 and 1996 in the Doubs Cancer Registry (France)., Results: The numbers of patients were 849 (31.8%) in rural areas and 89 (3.3%) in very rural areas. The relative 5-year survival was 15.2% in rural areas and 13.4% in urban areas (p = 0.5), and 2.7% in very rural areas and 14.4% in extended urban areas (p = 0.02). Multivariate analyses of observed and relative survival showed that patients living in very rural areas (p < 0.0001), 65 years of age and older and having small cell carcinoma had a significantly shorter survival., Conclusions: This study showed that the multidimensional definition of rurality identified a population with unfavorable prognoses.

Background: The authorities advocate a minimalist attitude towards the follow-up of resected bronchial carcinoma (clinical examination and chest x-ray). A survey showed that 70% of French respiratory physicians have chosen to use the CT scanner and often endoscopy. The published data are equivocal and are often based on retrospective studies. Lung cancer is a good model for a study of post-operative surveillance. Recurrences often occur in easily observed areas, they may be detected while still asymptomatic and are sometimes potentially curable. Second primary tumours may develop at the same site., Methods: The Intergroupe Francophone de Cancerologie Thoracique (IFCT) has initiated a trial comparing simple follow-up (clinical examination, chest x-ray) with a more intensive follow-up (CT scan, fibreoptic bronchoscopy). The surveillance will take place every 6 months for 2 years and then annually until 5 years., Expected Results: The main aim is to determine whether intensive follow-up improves patient survival. The opposite question is equally important. If an expensive and demanding follow-up does not affect the chances of cure these results will influence our practice.

The first meta-analysis of preoperative chemotherapy in non-small cell lung cancer (NSCLC) was published by Berghmans et coll. It included the first six reported studies and, despite the small number of patients involved, concluded in favour of preoperative chemotherapy. These six trials are summarized here. There are three other trials, which were not included in this meta-analysis; the SWOG study which was presented at the ASCO meeting in 2005 and an Italian and a Spanish trial, the results of which are still awaited. The advantages of preoperative chemotherapy are discussed. There are two other trials, whose designs are very different. The objective of the study by Albain et coll. was to evaluate the role of surgery after induction chemo-radiation in stage IIIa NSCLC. The results seem to be encouraging in patients who can undergo a (bi)lobectomy. The objective of the second trial was to evaluate whether surgery could improve survival after chemotherapy compared to thoracic irradiation in unresectable stage III disease. Although chemotherapy probably increased resectability, survival was not improved in operated patients.

The definition of appropriate use of drugs is questioned in oncology. Daily therapeutic practices were compared to official labelling and to published scientific data in this retrospective study. It was carried out in two respective specialised centers, from January to September 2004. All chemotherapies administered for adult solid tumours and including one of the eleven studied drugs were evaluated. The analysis of use was performed by drug : conformity to the validated labelling and level of scientific evidence (at the period study). The study included 1,561 drug uses in 1,211 patients. The overall rate of conformity to official labelling was 81.7 % (67.1 % of strict conformity). In 73.8 % of cases, the indications were supported by at least one randomized phase III trial. The results appeared to be significantly different in rare tumours. The potential economic stake of the "contrat de bon usage" was estimated as less than 5 % in our study. This analysis showed an appropriate and controlled use of onerous drugs in solid tumours. The official labelling of drugs are unable to answer to all clinical situations. The definition of a sufficient level of evidence is mandatory for the use of scientific data in clinical practice. This process has to be adapted for rare tumours.

Introduction: We designed this phase II trial to evaluate the efficacy and safety of weekly paclitaxel in combination with monthly carboplatin as first-line treatment in elderly patients with advanced non-small cell lung cancer (NSCLC)., Methods: Main eligibility criteria were histologically or cytologically proven stage IIIB or IV NSCLC, age > or =70 years, Eastern Cooperative Oncology Group performance status 0-2, and measurable disease. The 4-week-based chemotherapy regimen consisted of carboplatin infusion (area under the concentration-time curve 6 mg/ml/min) on day 1 and paclitaxel 90 mg/m as a 1-hour infusion on days 1, 8, and 15. Tumor response was evaluated using Response Evaluation Criteria in Solid Tumors criteria, and symptoms were evaluated using the Lung Cancer Symptoms Scale. Analyses were performed on an intention-to-treat basis., Results: From February 2002 to August 2003, 51 patients (median age, 74 years) participated in the study. One complete and 21 partial responses were reported by the independent review committee, leading to an intention-to-treat objective response rate of 43% (95% confidence interval, 30-57%). The median progression-free and overall survivals were 7.5 (95% confidence interval, 6.2-9.4) and 13.6 (95% confidence interval, 7.5-17) months, respectively. Longitudinal evaluation of the Lung Cancer Symptoms Scale demonstrated lack of quality of life modification during the treatment period. Neurotoxicity was mild to moderate, with 6% of patients suffering from a grade 3 or 4 neuropathy. Myelosuppression was the main toxicity; 39% of patients experienced grade 3 or 4 neutropenia, 18% experienced grade 3 anemia, and 8% experienced grade 3 or 4 thrombocytopenia. There was no treatment-related death., Conclusions: The combination of weekly paclitaxel 90 mg/m administered on days 1, 8, and 15 plus monthly carboplatin area under the curve 6 on day 1 of a 4-week cycle was feasible and active as a first-line treatment for elderly patients with NSCLC with a good safety profile. These results deserve further analysis to compare the standard care for these patients (monotherapies) with this doublet.

In this phase II study, gemcitabine and vinorelbine were combined at suboptimal doses for weekly administration in advanced non-small cell lung cancer (NSCLC). The primary objectives were to determine objective response rate (ORR) and time to progression (TTP). Secondary endpoints were safety and overall survival. Chemonaive patients with histologically or cytologically confirmed stage IIIB or IV NSCLC received vinorelbine (25 mg/m2) immediately followed by gemcitabine (800 mg/m2) once each week (on day 1) for 6 months without rest. From May 1998 to May 1999, 40 patients were enrolled (85% males; 70% stage IV) with a median age of 65.5. A total of 478 doses were administered, with a median of 9 per patient (range 2-72). The ORR was 27.5% (95% CI, 15.1-44.1%). The median TTP was 3.5 months (95% CI, 2.9-4.4 months). At a median follow-up of 6.5 months, the median survival was 11.6 months, and survival rates at 1 and 2 year(s) were 47.5% and 15.8%, respectively. The most common grade 3/4 hematologic toxicity was neutropenia, in 70% of patients, with febrile neutropenia in 28%. The most common grade 3/4 non-hematologic toxicity was transaminase elevation, in 22.5% of patients, which was transient and reversible. The other most prominent toxicities were, unexpectedly, pulmonary and cardiac toxicities. Based on these results, weekly, long-term administration of gemcitabine-vinorelbine appears to be an active regimen in NSCLC that warrants further investigation.

Pre-operative chemotherapy for non-small cell bronchial carcinoma (NSCLC) has the twin objectives of destruction of micrometastases and increased resectabilty of the primary tumour. The trials of Rosell and Roth showed weak benefits in favour of the combination. In the French trial overall survival was no different for the whole group but was improved in early stage disease. Preliminary results of the SWOG trial show a non-significant difference in 2 year survival of 6%. The EORTC 08941 trial showed no difference between surgery and radiotherapy following induction chemotherapy in non-resectable stage IIIAN2 NSCLC. The INT-0139 trial compared surgery following induction chemo-radiotherapy with chemo-radiotherapy alone. There was no difference between the two strategies but analysis of sub-groups suggested that some groups might benefit from the triple combination. Two further trials await publication. The small number of patients in each trial suggests that a meta-analysis will be necessary to reach a definite conclusion. The combination of surgery and chemotherapy is becoming standard in stage II disease. Only the timing, pre- or post-operative, remains controversial. At present, of the original objectives, only the destruction of micro-metastases has been confirmed.

Invasion of bone by a metastatic lesion is the most common cause of pain in cancer patients. Pain management in these patients is an important and difficult task. The pain is not always properly controlled by high doses of specific medication, radiation therapy or chemotherapy. When these therapies do not provide adequate pain relief, percutaneous vertebroplasty, cementoplasty, radiofrequency ablation and internal radiotherapy appear to be elegant and efficient complementary alternative pain control methods.

Background: Pathologic complete response (CR) to preoperative chemotherapy has been shown to be a strong prognostic factor in resected non-small cell lung cancer (NSCLC). This preoperative setting offers the opportunity to evaluate the clinical prediction of CR by investigators and an evaluation committee (EC) using the "gold standard" pathologic examination as the reference. The only published large randomized trial of preoperative chemotherapy (to our knowledge), the French neoadjuvant study, constitutes an interesting database to evaluate CT scan-based CR assessment. STUDY OBJECTIVES AND DESIGN: The French trial compared mitomycin-ifosfamide-cisplatin followed by surgery with surgery alone in stage I (except T1N0) to IIIa resectable NSCLC. Response was prospectively assessed in all patients receiving preoperative chemotherapy by the investigator in charge of the patient and by an EC, and was compared with pathologic postoperative data., Results: In the preoperative chemotherapy study, 167 patients were operated on. Nineteen patients were found to have a pathologic CR. Only seven patients were classified as having a CR by investigators and five patients by the EC. Evaluation of CR was correct in six of these seven cases and in three of these five cases, respectively. Sensitivity of the CR diagnosis was 31.6% for investigators and 15.8% for the EC. Specificities of the CR diagnosis were 99.4% and 98.8%, respectively. Positive predictive values were 85.7% and 60%, respectively. Negative predictive values were 91.9% and 90.1%, respectively. Accuracies were 91.6% and 89.2%, respectively., Conclusion: Investigator assessment of CR was highly predictive of pathologic CR. However, this study showed that clinical CT scan-based assessment, whether performed by investigators or the EC, underestimated the frequency of CR after preoperative chemotherapy in resectable NSCLC.

Purpose: To determine whether BMS-275291, a broad-spectrum matrix metalloproteinase inhibitor (MMPI), added to systemic chemotherapy improved survival in advanced non-small-cell lung cancer (NSCLC). In early phase studies, BMS- 275291 was not associated with dose-limiting joint toxicity seen with other MMPIs., Patients and Methods: Chemotherapy-naive patients with stage IIIB/IV NSCLC, performance status (PS) 0 to 2, and adequate organ function were eligible. All patients received paclitaxel 200 mg/m2 plus carboplatin (area under the curve, 6 mg/mL-min) intravenously every 21 days for up to 8 cycles, and were randomly assigned to receive BMS-275291, 1,200 mg orally daily, or placebo until disease progression. The primary study end point was survival (OS); secondary end points included progression-free survival (PFS), response rates (RR), toxicity, and quality of life., Results: From 2000 to 2002, 774 patients were randomly assigned. Pretreatment characteristics were well balanced between arms: median age, 61 years; male sex, 73%; stage IV, 79%; PS 0 to 1, 88%. Interim safety analysis revealed no survival advantage and increased toxicity in the experimental arm, and study treatment was stopped. Median OS, PFS and RR in the final analysis in the BMS-275291 arm were 8.6 months, 4.9 months, and 25.8% respectively, and in the control arm 9.2 months, 5.3 months, 33.7%. Toxicity was significantly higher in the BMS-275291 arm, including flu-like symptoms, rash, hypersensitivity reactions (8.6% v 2.4%), and febrile neutropenia (9.7% v 5.5%)., Conclusion: BMS-275291 added to chemotherapy increases toxicity and does not improve survival in advanced NSCLC.

Background: Prolongation of chemotherapy duration, usually referred to as maintenance chemotherapy, has been considered as an approach to improve survival of patients with advanced non-small-cell lung cancer (NSCLC). If the maintenance regimen differs from the induction regimen, patients will receive not only higher total doses of chemotherapy but also earlier delivery of non-cross-resistant agents. We conducted a randomized trial to compare maintenance vinorelbine therapy with observation in previously untreated patients who responded to induction treatment with mitomycin-ifosfamide-cisplatin (MIC)., Methods: Patients with stage IIIB NSCLC were treated with two monthly MIC cycles followed by radiotherapy; those with "wet" stage IIIB (pleural or pericardial involvement), with stage IIIB with supraclavicular node involvement, or stage IV (i.e., metastatic) NSCLC were treated with four monthly MIC cycles. Patients who responded to induction treatment were randomly assigned to receive intravenous vinorelbine at a dose of 25 mg x m(-2) x wk(-1) for 6 months or no further treatment. Survival comparisons used the log-rank test and the Cox regression adjusted for stage. All statistical tests were two-sided., Results: A total of 573 patients were registered, of whom 227 responded to induction treatment and 181 were randomly assigned (91 to maintenance vinorelbine and 90 to observation) between January 1994 and March 2000. One- and 2-year survival rates were 42.2% and 20.1% in the vinorelbine arm and 50.6% and 20.2% in the observation arm, respectively (log-rank P = .48). The hazard ratio of survival after adjustment on stage, in the vinorelbine arm relative to the observation arm, was 1.08 (95% confidence interval = 0.79 to 1.47; P = .65). There was also no difference between arms in progression-free survival (log-rank P = .32)., Conclusion: Maintenance vinorelbine did not improve survival of patients with advanced NSCLC who responded to induction MIC treatment. Nevertheless, other agents, including docetaxel and targeted agents, should be evaluated as maintenance agents before the concept is abandoned.

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/m(2) days 1 and 8 plus docetaxel 85 mg/m(2) day 8, every 3 weeks for eight cycles) or CV (cisplatin 100 mg/m(2) day 1 plus vinorelbine 30 mg/m(2), 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.

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.

Chemotherapy (CT) combined with surgery in non-small cell lung cancers has been studied for a number of years. It can be used prior to or following surgery (adjuvant). A long rather unfruitful period ended with the meta-analysis of the Non-Small Cell Cancer Collaborative Group, published in the British Medical Journal in 1995 that suggested an increase in survival of 5% at 5 years with the addition of adjuvant chemotherapy to surgery. Since this publication, arguments have accumulated in favour of this combination. Phase II studies have shown the feasibility of pre-surgical CT. A randomised trial in France showed a near 10% improvement in survival at 5 years, approaching statistical significance, and that this beneficial effect was further enhanced in the early stages of cancer. Excess post-surgical morbidity and mortality, even though non-significant, emphasizes the need for an effective but less toxic CT than the mitomycine-ifosfamide-cisplatin combination initially selected. In the field of adjuvant CT, the arguments in favour of the association have accumulated with the positive results of 3 studies, the IALT trial, the BR10 trial of the Canadian National Cancer Institute and the 9633 trial of the CALGB, with the latter two studies presented this year at the American Society of Clinical Oncology meeting. Four other pre-surgery CT trials are ongoing, but their results will not be available for several years. When choosing optimal timing among the various CT administration methods, before or after surgery, the arguments are in favour of pre-surgery CT: the possibility of assessing the chemosensitivity of the tumor, permitting the early withdrawal of treatment if it fails (presently in 40% of patients), the enhanced acceptability of CT by the patients, and the increase in resectability of the tumours. Conversely, however, one must note the greater difficulty for staging and the increase in post-surgical risks, basically in N2 patients, which will gradually lead to its replacement by the use of 3rd generation CT.

Brain metastases are a frequent feature of the course of non-small cell lung carcinoma (NSCLC). The potential usefulness of prophylactic cranial irradiation (PCI) has led to the search for target groups likely to derive benefit. This multivariate analysis looked for factors predictive of brain metastases in a group of stages I-III NSCLC patients under care of the thoracic oncology unit of Besançon University Hospital from 1977 to 2001. All the patients had the same follow-up. They were divided into two groups: BM+ when they had a brain metastasis as the first site of progression, whether solitary or not, and BM(-) otherwise. Variables analysed were age, gender, performance status (0-1 versus 2-3), weight-loss stage T-status, N-status, pathological type, type of treatment, administration of chemotherapy, use of cisplatin and response to treatment. Three hundred and five patients were eligible and there were 77 patients (25.25%) in the BM+ group. Median time to onset of brain metastases was 12 months (1-163 months) and median survival from the diagnosis of brain metastases was 6 months (1-65 months). Factors predictive of brain progression were age < or =62 years (RR: 2.5, 95% CI: 1.33-4.76 and P = 0.004), T4 tumour status (RR: 3.75, 95% CI: 1.72-8.21 and P = 0.0009), N2-3 (RR: 2.61, 95% CI: 1.32-5.15 and P = 0.0057), and adenocarcinoma (RR: 3.39, 95% CI: 1.78-6.46 and P = 0.0002). No aspect of treatment plays a role in the frequency of this type of metastasis. These factors predictive of brain progression could serve as a basis for the selection of patients with the aim of sitting of studies on prophylactic cranial irradiation in NSCLC.

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/m(2) (arm A) or 100 mg/m(2) (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/m(2), as it has a more favourable safety profile and on balance a similar efficacy to the 100 mg/m(2) dose.

Aims: To compare respiratory status in dairy farmers with that of non-farming controls., Methods: Longitudinal study in the Doubs (France). From a cohort constituted in 1994 (T1), 215 (81.1%) dairy farmers and 110 (73.8%) controls were reevaluated in 1999 (T2). The protocol comprised a medical and occupational questionnaire, spirometric tests at both evaluations, allergological tests at T1, and a non-invasive measure of blood oxygen saturation (SpO2) at T2., Results: In 1999 analyses, the prevalence of chronic bronchitis was higher (p = 0.013), and FEV1/VC (p < 0.025) and SpO2 (-0.7%, p < 0.01) lower in dairy farmers than in controls. In a multiple linear regression model, farming, age, and smoking were significantly and inversely correlated with SpO2. In the whole population, the mean annual decline in FEV1 and FEV1/VC was -13.4 ml and -0.30%, respectively. Farming was associated with an accelerated decline in FEV1/VC (p < 0.025) after adjustment for covariates. No relation between allergy and respiratory function changes was observed, except for FEF25-75., Conclusions: This prospective study shows that dairy farming is associated with an excess of chronic bronchitis, with a moderate degree of bronchial obstruction and a mild decrease in SpO2.

Context: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French cancer centers and specialists from French public university and general hospitals and private clinics. Its main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery., Objectives: To develop, according to the definitions of the Standards, Options and Recommendations, clinical practice guidelines for the management of non small cell lung carcinoma patients., Methods: Data were identified by searching Medline and the personal reference lists of members of the expert groups, then submitted for review to independent reviewers. This is a short version of the SOR guideline covering diagnosis, treatment and follow-up and includes the algorithms for the management of patients with non-small cell lung cancer.

Among all nonmetastatic non-small-cell lung cancer (NSCLC) patients, the best survival rates are observed in patients who undergo surgery. Nevertheless, 5-year survival rates vary between 20% and 60% depending on the stage of the disease. Several combined modality treatments have been investigated to improve outcome in localized NSCLC. These include local treatment, systemic before local treatment, concomitant systemic and local treatments, and systemic after local treatment. Preoperative irradiation was shown to be of no benefit on local recurrence rates or overall survival. Even doses of radiation >/=40 grays (Gy) were associated with lower survival rates. Postoperative irradiation did not influence survival in stage III disease and seemed to be deleterious in stages I and II disease. Modern radiotherapy techniques might be of interest in this setting but have been insufficiently tested. The early phase III studies of preoperative chemotherapy versus primary surgery in stage III NSCLC showed a tremendous difference in favor of chemotherapy. A larger study did not confirm these results but suggested that preoperative chemotherapy might have a greater effect in stages I and II of the disease. In locally advanced disease, chemotherapy followed by radiotherapy was shown to increase survival when compared with radiotherapy alone. Studies comparing concurrent chemoradiation with radiotherapy only were in favor of the concomitant schedule, which improved local control. Promising results have been reported with chemoradiation followed by surgery in stage IIIa and even stage IIIb disease. Randomized studies of postoperative chemotherapy demonstrated a 5% improvement in 5-year survival over adjuvant-free treatment. Postoperative chemoradiation showed no advantage over postoperative radiotherapy. Several trials that are ongoing or whose accrual was recently completed should further define the role of perioperative chemotherapy in resectable NSCLC and of trimodality treatments in advanced disease. Targeted agents are being developed in the postoperative setting. New schedules of chemoradiation with higher therapeutic indexes are also being investigated in nonresectable stage III NSCLC.

Context: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French cancer centers (FNCLCC), the 20 French cancer centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery., Objectives: To develop clinical practice guidelines for non small cell lung cancer patients according to the definitions of the Standards, Options and Recommendations project., Methods: Data were identified by searching Medline , web sites, and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers., Results: This article presents the chapter "Prognosis significance of oncogenes and tumor suppressor genes" from the full report "Standards, Options and Recommendation for non small cell lung cancer" validated in August 2000. The main recommendations are: 1) No clear clinical prognostic value of oncogenes and tumor suppressor genes (p53, bcl-2, Ki-ras, c-erbB-2, Rb, p16) in non small cell lung cancer, can be established from the available evidences (standard, level of evidence C). 2) Prospective multicenter studies should be performed to assess prognostic significance of oncogenes and tumor suppressor genes in non small cell lung cancer.

Preoperative chemotherapy is a real challenge in the treatment of non-small cell lung cancer. From the first phase II studies, we have learned that response rates to preoperative chemotherapy were high, around 70% with approximately 10% of complete responses. Although toxicity seemed acceptable, increased morbidity and mortality were observed and have to be taken into account for the choice of the preoperative chemotherapy regimen. Two randomized trials were initially conducted in stage IIIA disease and showed highly positive survival results. However, only few patients had been included in both studies, and their statistical value has been considered as questionable. The French MIP91 study, whose results have been published in 2002, argues in favour of preoperative chemotherapy but could not demonstrate a clear-cut advantage. New studies are ongoing. In the search of effective and less toxic combinations, cisplatin-gemcitabine has a role to play. Several phase II studies of this regimen have been presented at the last meeting of the American Society of Clinical Oncology (ASCO) in the preoperative setting or in combination with radiotherapy, and confirmed its efficacy and good tolerability. Chemoradiation is important as part of the trimodality strategy including chemotherapy, radiotherapy, and surgery, which might become standard of care in the treatment of stage IIIa disease.

Surgery has long been considered standard treatment in early stage non-small cell lung cancer. Preoperative chemotherapy is a real challenge in the treatment of these stages. Some conclusions can be drawn from the first phase II studies in stage IIIA tumors. Response rates were higher than those observed in stage IV tumors, reaching approximately 70%. Although toxicity seemed acceptable, increased morbidity and mortality have to be taken into account for the choice of preoperative regimens. Two randomized studies that included only a few patients were conducted in stage IIIA disease and showed highly positive survival results. The French randomized study argued in favor of preoperative chemotherapy with an absolute difference in survival rates that remains constant beyond the third year. New studies are ongoing to evaluate the role of the gemcitabine/cisplatin combination. Several phase II studies of this regimen in the preoperative setting or in combination with radiotherapy have been presented at the most recent meetings of the American Society of Clinical Oncology. These studies confirmed both its efficacy and good tolerability. In several ongoing randomized studies, this combination has been chosen to test the concept of preoperative chemotherapy. One such study, which compares two different strategies of preoperative chemotherapy, is by the Intergroupe Francophone de Cancérologie Thoracique., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

TO PROLONG SURVIVAL: Systemic neo-adjuvant chemotherapy attempts to reduce the development of metastases. Data available on neoadjuvant chemotherapy of NSCLC come from three types of clinical trials. NEO-ADJUVANT CHEMOTHERAPY PHASE II TRIALS: Many trials have demonstrated that the neo-adjuvant approach is feasible, that it leads to a high rate of response, to the order of 50 to 70%, that it does not compromise surgery, and exhibits acceptable toxicity. High survival rates have been obtained, notably in total responders. NEO-ADJUVANT CHEMO-RADIOTHERAPY PHASE II TRIALS: Have essentially demonstrated that this approach is feasible, exhibits acceptable toxicity, worse in pneumonectomy. High response rates have been obtained and relative improved survival, since most of the cases concerned extensive forms that could not be treated surgically. RANDOMIZED PHASE III TRIALS: Gave varying results: two of them only concerned small series of patients (60 in all) with stage IIIA NSCB, with positive results. The third study concerned 373 patients with stage I, II and IIIA cancers: survival at 3 years was increased by 11%, but this difference is not yet significant. Benefits were essentially apparent for stage I and II patients., In the Future: Continued active clinical research, oriented differently, on stage I and II, and stage IIIA is necessary.

Pronostic of lung carcinoma is very poor but, every year in Europe and North America, thousands of patients are offered a chance of cure. However only a long period of time without relapse allows to state the reality of cure. Sequelae generated by cancer treatments are potentially increased by the use of treatments combinations. In operated patients, chronic respiratory insufficiency is the most common late complication often interfering with professionnal activity especially for manual workers. Late toxicity after radiotherapy for lung cancer has been little studied. Thoracic irradiation especially affects lung and cardiac functions. Late toxicity of chemotherapy may be more frequent with the increasing use of neoadjuvant chemotherapy before surgery or radiotherapy in patients potentially cure.

Purpose: To evaluate whether preoperative chemotherapy (PCT) could improve survival in resectable stage I (except T1N0), II, and IIIA non-small-cell lung cancer (NSCLC)., Patients and Methods: A randomized trial compared PCT to primary surgery (PRS). PCT consisted of two cycles of mitomycin (6 mg/m(2), day 1), ifosfamide (1.5 g/m(2), days 1 to 3) and cisplatin (30 mg/m(2), days 1 to 3), and two additional postoperative cycles for responding patients. In both arms, patients with pT3 or pN2 disease received thoracic radiotherapy., Results: Three hundred fifty-five eligible patients were randomized. Overall response to PCT was 64%. There were two preoperative toxic deaths. Postoperative mortality was 6.7% in the PCT arm and 4.5% in the PRS arm (P =.38). Median survival was 37 months (95% confidence interval [CI], 26.7 to 48.3) for PCT and 26.0 months (95% CI, 19.8 to 33.6) for PRS (P =.15). Survival differences between both arms increased from 3.8% (95% CI, 1.3% to 25.1%) at 1 year to 8.6% (95% CI, 2.64% to 24.4%) at 4 years. A quantitative interaction between N status and treatment was observed, with benefit confined to N0 to N1 disease (relative risk [RR], 0.68; 95% CI, 0.49 to 0.96; P =.027). After a nonsignificant excess of deaths during treatment, the effect of PCT was significantly favorable on survival (RR, 0.74; 95% CI, 0.56 to 0.99; P =.044). Disease-free survival time was significantly longer in the PCT arm (P =.033)., Conclusion: Although impressive differences in median, 3-year, and 4-year survival were observed, they were not statistically significant, except for stage I and II disease.

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 discontinuation 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/m2/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.

Preoperative chemotherapy has been intensively studied in stage IIIA non-small cell lung cancer and, to a lesser extent, in stage IIIB. For a considerable time period, early stage non-small cell lung cancer was dropped from studies. For early investigators, shrinking the tumor size, thus allowing complete resection of initially unresectable tumors, appeared as important as destroying micrometastases. Nevertheless, analysis of relapse patterns shows that preoperative chemotherapy appears to act more on micrometastases than on local control. The first randomized studies of preoperative chemotherapy were conducted only among patients with stage IIIA disease. The French Cooperative Oncology Group presented a large randomized study among 373 stage IB, II, and IIIA patients at the American Society of Clinical Oncology meeting in May 1999. A Cox multivariate analysis showed a protective effect of preoperative chemotherapy, and this effect seemed to preferentially involve patients with early stage disease. Ongoing studies of most US and European oncology groups are including early stage tumors, as in the Southwest Oncology Group trial 9901. The new Intergroupe Francophone de Cancérologie Thoracique also is ready to start a preoperative randomized chemotherapy study in stage I and II non-small cell lung cancer, that will compare two different strategies of preoperative chemotherapy in responding patients. Patients will be randomized to two groups: one group will receive chemotherapy before surgery and the other group will receive it before and after surgery., (Copyright 2001 by W.B. Saunders Company.)

Context: The 'Standards, Options and Recommendations' (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French cancer centres and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery., Objectives: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the management of stage I and II non small cell lung carcinoma treated by radiotherapy alone., Methods: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French cancer centres., Results: The main recommendations for the management of stage I and II non small cell lung carcinoma treated by radiotherapy alone are: 1) The curative external irradiation with a continual course is an alternative to surgery only in the case of medically inoperable tumors or because the patient refuses surgery; 2) The external irradiation of the primary tumor only without the mediastinum could be proposed in peripheral stage IA. In proximal stage IA and IB, external irradiation should be carried out only as part of prospective randomised controlled trials comparing a localised irradiation of the primary tumor with a large irradiation of the mediastinum and the primary tumor. The treated volume must include the macroscopic tumoral volume with or without the microscopic tumoral volume and with a security margin from 1.5 to 2 cm; 3) There is a benefit to delivering a total dose in the primary tumor higher than 60 Gy in so far as the proposed irradiation, taking into account the respiratory function, does not increase the likelihood of severe adverse events due to radiation; and 4) The change in fractionation, the radiochemotherapy combination, the endobronchial brachytherapy with high dose rate alone or with external irradiation could be proposed only as part of prospective controlled trials for tumors classified as stage IB or II.

A multi-centre retrospective study involving 4 French university institutions has been conducted in order to identify routine pre-therapeutic prognostic factors of survival in patients with previously untreated non-small cell lung cancer and brain metastases at the time of presentation. A total of 231 patients were recorded regarding their clinical, radiological and biological characteristics at presentation. The accrual period was January 1991 to December 1998. Prognosis was analysed using both univariate and multivariate (Cox model) statistics. The median survival of the whole population was 28 weeks. Univariate analysis (log-rank), showed that patients affected by one of the following characteristics proved to have a shorter survival in comparison with the opposite status of each variable: male gender, age over 63 years, poor performance status, neurological symptoms, serum neuron-specific enolase (NSE) level higher than 12.5 ng ml(-1), high serum alkaline phosphatase level, high serum LDH level and serum sodium level below 132 mmol l(-1). In the Cox's model, the following variables were independent determinants of a poor outcome: male gender: hazard ratio (95% confidence interval): 2.29 (1.26-4.16), poor performance status: 1.73 (1.15-2.62), age: 1.02 (1.003-1.043), a high serum NSE level: 1.72 (1.11-2.68), neurological symptoms: 1.63 (1.05-2.54), and a low serum sodium level: 2.99 (1.17-7.62). Apart from 4 prognostic factors shared in common with other stage IV NSCLC patients, whatever the metastatic site (namely sex, age, gender, performance status and serum sodium level) this study discloses 2 determinants specifically resulting from brain metastasis: i.e. the presence of neurological symptoms and a high serum NSE level. The latter factor could be in relationship with the extent of normal brain tissue damage caused by the tumour as has been demonstrated after strokes. Additionally, the observation of a high NSE level as a prognostic determinant in NSCLC might reflect tumour heterogeneity and understimated neuroendocrine differentiation., (Copyright 2001 Cancer Research Campaign.)

Surgery has been considered the standard of care in patients with early-stage non-small cell lung cancer (NSCLC), as well as in some cases of stage III, for a long time. Poor survival after complete resection has led to the search for new therapeutic strategies such as combining anticancer treatments. However, at the present time, attempts to combine chemotherapy and radiotherapy after surgery have failed to show any significant impact on survival among patients with completely resected NSCLC., (Copyright 2001 Harcourt Publishers Ltd.)

Context: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery., Objectives: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the management of locally advanced non small cell lung carcinoma., Methods: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers and to the medical committees of the 20 French Cancer Centres., Results: The main recommendations are: 1) The management of the locally advanced non small cell lung carcinoma has two main goals: firstly to obtain local control of the disease (or to at least delay local progression in order to improve the survival or relapse free survival), and secondly to prevent the development of metastases. 2) There is a consensus that locally advanced non small cell lung carcinoma should be irradiated. External beam radiotherapy should be of optimal quality and delivered at a minimal dose of 60 Gy by standard fractionation. For patients with a poor life expectancy, this can be delivered as a split-course or hypofractionated scheme. 3) Treatment for patients with a performance status of 0-1 should consist of short duration induction chemotherapy (with a least two drugs one of which must be cisplatin), combined sequentially with conventional radiotherapy. 4) Surgery is contraindicated in extensive N3 disease. Combined radio-chemotherapy (adjuvant or neoadjuvant) is not indicated outside clinical trials. Surgery is justified in stage N2 disease as good local control can be achieved. T4-N0 disease should be treated surgically with curative intent.

A dose escalation study of paclitaxel in combination with vinorelbine was conducted in 21 patients with previously untreated stage IIIb or IV non-small cell lung cancer (NSCLC). All three patients treated with the initial dose of paclitaxel 135 mg/m(2) administered as a 1-h intravenous infusion and vinorelbine 25 mg/m(2) experienced dose-limiting toxicity (febrile neutropenia). After modification of the dosing schedule, the MTD of paclitaxel was found to be 115 mg/m(2) when combined with vinorelbine 20 mg/m(2) on day 1, followed by vinorelbine 20 mg/m(2) on day 5. Partial responses were achieved in 24% of patients, with a median duration of response of 126 days (range from 84 to 484 days) and a 1-year survival rate of 42%. In conclusion, haematologic toxicity (febrile neutropenia/neutropenia) severely restricts the dosing schedule of combined paclitaxel and vinorelbine, and possibly limits anti-tumour efficacy.

Objective: To assess the lung cancer patient's prognosis in the intensive care unit with early predictive factors of death., Design: Retrospective study from July 1986 to February 1996., Setting: Medical intensive care unit at a university hospital., Patients: Fifty-seven patients with primary lung cancer admitted to our medical intensive care unit (MICU)., Measurements and Results: Data collection included demographic data (age, sex, underlying diseases, MICU admitting diagnosis) and evaluation of tumor (pathologic subtypes, metastases, lung cancer staging, treatment options). Three indexes were calculated for each patient: Karnofsky performance status, Simplified Acute Physiology Score (SAPS) II, and multisystem organ failure score (ODIN score). Mortality was high in the MICU: 66% of patients died during their MICU stay, and hospital mortality reached 75%. In multivariate analysis, acute pulmonary disease and Karnofsky performance status < 70 were associated with a poor MICU and post-MICU prognosis. For the survivors, long-term survival after MICU discharge depended exclusively on the severity of the lung cancer., Conclusions: We confirmed the high mortality rate of lung cancer patients admitted to the MICU. Two predictive factors of death in MICU were identified: performance status < 70 and acute pulmonary disease.

An impairment of respiratory function has been demonstrated in dairy farmers. The objective of this study was to evaluate the relationship of allergy to respiratory function in dairy farmers in a longitudinal study conducted in the Doubs (France). A cohort of male dairy farmers constituted in 1990 was re-evalued in 1995. Subjects completed a medical and occupational questionnaire, and a spirometry test in both 1990 and 1995, in 1995 they were also subjected to immunological tests. Relationships between immunological variables and respiratory function were studied by a multiple linear regression model adjusted for age, smoking status, respiratory symptoms, altitude and occupational exposure. Amongst the 394 subjects of the initial cohort, 330 were included in the longitudinal study and 320 had immunological tests. Log immunoglobulin (Ig) E was negatively correlated with the 1995 respiratory function parameters (p<0.05 for forced expiratory volume in one second (FEV1) and FEV1/vital capacity (VC). Immunoglobulin (Ig) G response to Aspergillus fumigatus detected by enzyme-linked immunosorbent assay (ELISA) was negatively correlated to 1995 respiratory function parameters (VC: p<0.01; FEV1: p<0.001; FEV1/VC: p<0.01). There was a positive relationship between IgG antibodies against Aspergillus fumigatus and the mean annual decline in FEV1 (p<0.01) and FEV1/VC (p<0.01). To conclude, allergy may play a role in the impairment of respiratory function in dairy farmers of the Doubs and sensitization to Aspergillus fumigatus seems to constitute an independent risk factor for the development of airflow obstruction in this occupational setting.

A 47-year-old woman, without significant past medical history, presented an acute dyspnea with hypoxia, marked pulmonary arterial hypertension (PAH) and signs of right heart failure. Chest x-ray showed a moderate dilatation of the right heart cavities. Pulmonary embolism was suggested. After detailed questioning and complete explorations, a bird hypersensitivity pneumonitis (HP) was demonstrated. This case illustrates a misleading presentation of an acute form of HP consisting of apparently isolated PAH.