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A multicentre, single-arm, phase II trial designed to determine the efficacy of single-agent vinflunine in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with a platinum-based regimen. The objectives were to assess efficacy in terms of tumour response rate (primary end point), duration of response, progression-free survival (PFS) and overall survival (OS), and to evaluate the toxicity associated with this treatment. Patients with advanced NSCLC with progressive disease having failed prior platinum-based first-line treatment for advanced disease. Five responses out of the 63 treated patients were documented by WHO criteria and validated by an independent panel review (IRP), yielding a response rate of 7.9% (95% CI: 2.6-17.6) in the intent-to-treat analysis and 8.3% (95% CI: 2.8-18.4) in the evaluable population. Disease control was achieved in 35 out of 60 evaluable patients (58.3%). The median duration of response (complete response+partial response), according to modified WHO criteria was 7.8 months (95% CI: 4.6-NR). Median PFS was 2.6 months (95% CI: 1.4-3.8), and the median survival was 7.0 months (95% CI: 5.8-9.2). Grades 3-4 neutropenia was reported in 50% of patients; febrile neutropenia was observed in two patients (3.2%); grades 3-4 myalgia and grade 3 constipation were experienced by 10 (15.9%) and six (9.5%) of patients, respectively. Constipation was manageable, non-cumulative and could be prevented with laxative prophylaxis. The encouraging results from this phase II study with vinflunine warrant further investigations in phase III trials as second- or first-line treatment of advanced non-small-cell lung carcinoma, as a single agent or in combination with other active drugs.

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 Taxotere® (docetaxel) at the dose of 75 mg/m2 every 3 weeks is a standard therapy for pretreated non-small-cell lung cancer (NSCLC). The aim of this study was to evaluate the safety profile of two schedules of docetaxel administration (every 3 weeks versus weekly) in patients with pretreated NSCLC. Patients and methods From February 2000 to February 2001, 125 patients with locally advanced or metastatic NSCLC were randomised after failure of a previous platinum-based regimen to receive either docetaxel 75 mg/m2 administered every 3 weeks (Dq3w) or docetaxel 40 mg/m2 given weekly for 6 weeks followed by 2 weeks of rest (Dqw). Safety evaluations focused on grade 3–4 neutropenia, febrile neutropenia, nausea-vomiting and asthenia. Results Patients' characteristics were well balanced between arms. The most common National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3–4 toxicity was neutropenia, which occurred in 48.4% of Dq3w patients versus 15.9% of Dqw patients (P = 0.001). In addition, febrile neutropenia were observed in 6.5% of patients in Dq3w versus 0% in Dqw. Grade 3–4 asthenia was more frequent in Dqw. Other non-haematological toxicities were very rare. Regarding efficacy, there was a trend towards a better disease control rate in Dq3w: 32.2% versus 25.4% in Dqw. Median time to progression and survival were rather similar in both arms, respectively: 2.1 months (range 2–3.2) and 5.8 months (range 4.0–7.0) in Dq3w and 1.8 months (range 1.6–2.3) and 5.5 months (range 3.7–6.6) in Dqw. Conclusions While both schedules had a favourable safety profile, a significant lower rate of severe neutropenia was observed in the weekly arm. Both regimens had similar efficacy. The weekly regimen could be considered as a good alternative for patients at risk of severe neutropenia.

Resume Introduction Les donnees sur le cancer bronchique primitif (CBP) du sujet âge sont rares en France. Nous rapportons ici les resultats de l’etude KBP-2000-CHPG, ou 1 868 patients etaient âges de 70 ans et plus et 338 de 80 ans et plus. Methodes Nous avons compare les moins de 70 ans (groupe I) avec les 70 ans et plus (groupe II), ainsi que les specificites des 80 ans et plus. Resultats Le groupe II comprenait significativement plus de femmes (17,4 % vs 15,2 % ; p = 0,04), de non-fumeurs (11,2 % vs 5,3 % ; p Conclusions L’âge n’est donc pas a lui seul un facteur limitant du choix du traitement.

Resume La chimiotherapie des cancers bronchiques non a petites cellules au stade avance est fondee sur le cisplatine. Elle permet de prolonger la survie. Cependant, la toxicite elevee des associations de type doublets incluant le cisplatine impose la recherche d’alternatives. Les nouveaux cytotoxiques anti-cancereux ont un meilleur rapport efficacite : toxicite. Les doublets sans cisplatine, fondes sur de nouvelles molecules, constituent un espoir d’ameliorer la survie des malades sans deteriorer leur qualite de vie. Plusieurs etudes randomisees, a ce jour publiees ou presentees dans la maturite de leurs resultats, suggerent que certains doublets de nouveaux cytostatiques soient une alternative aux classiques doublets fondes sur le cisplatine. Les modifications recentes des recommandations de l’ American Association of Clinical Oncology tiennent comptent de ces recents resultats en admettant que “les chimiotherapies ne contenant pas de platine puissent etre utilisees comme une alternative aux chimiotherapies fondees sur le platine, en premiere ligne”. Cette breve revue de la litterature aborde les questions methodologiques soulevees par les publications des etudes randomisees evaluant essentiellement les doublets gemcitabine-vinorelbine ou gemcitabine-taxane, en les confrontant soit a des mono-chimiotherapies, soit a des chimiotherapies de reference fondees sur le cisplatine. Les criteres de jugement choisis dans de telles etudes sont discutes.

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.

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.

Contexte. - La Federation nationale des centres de lutte contre le cancer (FNCLCC) et les Centres regionaux de lutte contre le cancer (CRLCC), en collaboration avec des partenaires des secteurs public (CHU, CHG), prive et certaines societes savantes ont entrepris depuis 1993 d'elaborer des recommandations pour la pratique clinique en cancerologie: les « Standards, Options et Recommandations » (SOR). L'objectif de l'operation SOR est d'ameliorer la qualite et l'efficience des soins aux patients atteints de cancer en fournissant aux praticiens une aide a la decision facilement utilisable. La methodologie d'elaboration des SOR repose sur une revue et une analyse critique des donnees de la litterature scientifique par un groupe d'experts pluridisciplinaire, permettant de definir, sur la base du niveau de preuve scientifique et du jugement argumente des experts, des « Standards », des « Options » et des « Recommandations ». Avant publication, les SOR sont revus par des experts independants. Objectifs. - Definir, sur la base d'une revue de la litterature et de l'accord d'experts, des Standards, Options et Recommandations pour la prise en charge des patients atteints de cancer broncho-pulmonaire primitif de stade I ou Il traites par irradiation exclusive. Methodes. - Un groupe de travail multidisciplinaire mis en place par la Federation nationale des centres de lutte contre le cancer (FNCLCC) a revu les donnees scientifiques disponibles concernant la prise en charge des patients atteints de cancer broncho-pulmonaire primitif non a petites cellules de stade I et Il traites par irradiation exclusive. Apres selection des articles, synthese des resultats et redaction des SOR, le document a ete soumis pour relecture et approbation a des relecteurs. Resultats.- Les principales recommandations sont: 1) l'irradiation externe exclusive continue a visee curative, avec un fractionnement conventionnel, n'est une alternative a la chirurgie d'exerese qu'en cas de contre-indications a un acte chirurgical liees au terrain medical ou de refus du malade de tout acte chirurgical; 2) l'irradiation externe du volume tumoral primitif seul, sans le mediastin, peut etre proposee dans les formes classees stade IA, de topographie peripherique. Dans les formes classees stade IA proximal et IB, elle ne peut se concevoir que dans le cadre d'un essai therapeutique prospectif randomise et controle comparant une irradiation localisee au volume tumoral et une irradiation large mediastino-tumorale. Le volume traite doit inclure le volume tumoral macroscopique avec ou sans le volume tumoral microscopique, avec une marge de securite de 1,5 a 2 cm; 3) il y a un benefice a delivrer une dose totale dans le volume tumoral superieure a 60 Gy dans la mesure ou la technique d'irradiation proposee tenant compte de la fonction respiratoire du malade, n'augmente pas la probabilite de risque de complications severes radio-induites; 4) les modifications du fractionnement, l'association radiochimiotherapie concomitante, la curietherapie endoluminale a haut debit de dose seule ou en association a une irradiation externe, ne peuvent etre proposees que dans le cadre d'essais prospectifs controles pour des formes classees de stade IB ou II.

Purpose: To determine if the timing of whole brain radiotherapy (WBRT) with respect to chemotherapy with cisplatin and vinorelbine would influence survival in patients with non-small-cell lung cancer (NSCLC) and concurrent brain metastasis. Patients and methods; One hundred seventy-six patients with brain metastasis from NSCLC were included in the study between July 1995 and October 1997. All patients received chemotherapy with cisplatin 100 mg/m 2 on day 1 and vinorelbine 30 mg/m 2 on days 1, 8, 15, 22. Cycles were repeated every four weeks. Evaluation of response was performed after two, four or six cycles. After two cycles, chemotherapy was administered to the responders to a maximum of six cycles. Patients were randomised to receive WBRT 30 Gy/10 fx/12 days and delayed corticosteroids, (arm A) for the intracranial nonresponders, or early on day 1 to 12 during the first cycle of chemotherapy (arm B). Results: One hundred seventy-one patients were eligible: eighty-six in arm A and eighty-five in arm B; none had received prior chemotherapy; seventy-six and seventy-three, respectively, were assessable for response. There was a 21% overall objective response rate (OR) (with I complete response and 17 partial responses) after two cycles of chemotherapy alone (arm A) and a 20% OR (with 17 partial responses) to chemotherapy and early WBRT (arm B). The intracranial OR was 27% and 33%, respectively (P = 0.12). The six months survival rate (46% and 40%) and the median survival duration (24 and 21 weeks, respectively) were not significantly different between the two arms (P = 0.83, log-rank test). The major toxicity was severe or life-threatening neutropenia (grade 4), which occurred in 35% of arm A patients and 36% of arm B patients. There were thirteen treatment-related deaths (six in arm A and seven in arm B). There was no difference between the arms for haematological and neuro-toxicities. Conclusions: These results confirm the efficacy of chemotherapy in brain metastases of NSCLC and suggest that the timing (early or delayed) of WBRT did not influence survival of NSCLC with brain metastasis treated with concurrent chemotherapy.

This is an important contribution to the growing debate about the close links of polities to language, which is the innermost component of a nation and its culture, and the main support of the latter. Thus the book will be highly attractive to anyone interested in sociolinguistics and nation-building. It contains four parts: a general reflection on how language policy and linguistic culture have been perceived by scholars up to now, followed by studies of three national situations where these problems have been faced – France, India, and the US – with emphasis in each country on an important regional case (Alsace, Tamil Nadu, and California). Schiffman is able to speak about each case through personal experience of living and working on the spot.

We report the observation of a 55-year-old man in subtotal remission of a bronchial T2 N2 M1 adenocarcinoma. He consulted for left ocular redness, attributed to a foreign body. The patient presented a left iridal metastasis of bronchial carcinoma, a left frontal cerebral metastasis, and mediastinal evolutionary recovery. External radiotherapy of 30 Gy in ten fractions was immediately begun, followed by second-line chemotherapy. Local anatomical and functional recovery was fast. The patient then required two external radiotherapy courses on new extraocular lesions. The patient died 10 months after the ocular metastasis diagnosis. In the event of iridal metastasis, it is necessary to carry out a complete examination of both eyes, to question the patient, to search for a primary tumor and other metastases, and to rapidly implement radiotherapy of the entire ocular sphere (30 Gy in ten fractions).

The purpose of this epidemiologic survey was to describe the management of second-line therapy for patients with stage IIIB-IV non-small cell lung carcinoma (NSCLC) following docetaxel-cisplatin as first-line therapy.Between June 2003 and December 2004, 265 patients were enrolled. The data registered were the choice of cytotoxics, the safety profile, the efficacy and the clinical benefit.Two hundred and sixty one patients were treated with docetaxel-cisplatin as a first-line regimen and 181 received a second line. This second line was a single agent regimen in 58% of cases and a gemcitabine based treatment in 60.8%. The main criterion for the choice of second-line therapy was the safety profile in 34.3% of cases. The overall response rate was 16.6% after the second line and clinical benefit was reported in 43.6% of patients.In more than 2/3 of patients with NSCLC the docetaxel-cisplatin combination leaves the opportunity to give a second-line treatment, providing satisfying results in terms of clinical benefit. In this study gemcitabine was the most widely prescribed second-line treatment, mainly as a single agent.

There are few data on primary bronchial carcinoma in France. We report here the results of the study KBP 2000-CPHG in which there were 1868 patients aged 70 or more and 338 aged 80 or more.We compared the patients under 70 (Group I) with those aged 70 or more (Group II) as well as with the details of the over 80's.Group II included significantly more women (17.4% vs 15.2%; p = 0.04), non-smokers (11.2% vs 5.3%; p0.0001), patients of poor performance status (24.2% vs 14.5%; p0.0001) and squamous carcinomas (44.5% vs 37.8%; p0.001) than Group I, but fewer adenocarcinomas (27.2% vs 31.5%; p = 0.009) and as many small cell carcinomas (15.9% vs 16.9%; p = 0.32). In Group II there were less stage III and IV tumours (75.1% vs 78.1%; p = 0.0005) more symptomatic treatment (23.2% vs 6.1%) and radiotherapy alone (12.8% vs 3.8%; p0.0001). The results were similar beyond 80 years. On multivariate analysis age, performance status and stage appeared to be independent variables in the choice of curative or symptomatic treatment.Age alone is not therefore a limiting factor in the choice of treatment.

Chemotherapy of advanced non-small cell lung cancers is based on cisplatin, which prolongs survival. However, the high toxicity of double-type combinations including cisplatin warrants the search for alternatives. New anti-cancer cytotoxic agents exhibit improved efficacy-toxicity ratio. Bitherapy, without cisplatin and with new molecules, provides hope of improvement in survival without deterioration in quality of life. Several randomised trials, already published or presented with mature results, suggest that certain bitherapies with new cytostatic agents are an alternative to the classical cisplatin-based bitherapies. The recent modifications in the guidelines of the American Association of Clinical Oncology take into account these recent results by admitting that "chemotherapy without cisplatin can be used as an alternative to the first-line platin-based chemotherapies". This brief review of the literature underlines the methodological questions raised by the publication of randomised studies essentially assessing gemcitabine-vinorelbine or gemcitabine-taxane combinations, by confronting them with either mono-chemotherapies or reference chemotherapy based on cisplatin. The assessment criteria selected in such studies are discussed.

There are few data on primary bronchial carcinoma in France. We report here the results of the study KBP 2000-CPHG in which there were 1868 patients aged 70 or more and 338 aged 80 or more.We compared the patients under 70 (Group I) with those aged 70 or more (Group II) as well as with the details of the over 80's.Group II included significantly more women (17.4% vs 15.2%; p=0.04), non-smokers (11.2% vs 5.3%; p0.0001), patients of poor performance status (24.2% vs 14.5%; p0.0001) and squamous carcinomas (44.5% vs 37.8%; p0.001) than Group I, but fewer adenocarcinomas (27.2% vs 31.5%; p=0.009) and as many small cell carcinomas (15.9% vs 16.9%; p=0.32). In Group II there were less stage III and IV tumours (75.1% vs 78.1%; p=0.0005) more symptomatic treatment (23.2% vs 6.1%) and radiotherapy alone (12.8% vs 3.8%; p0.0001). The results were similar beyond 80 years. On multivariate analysis age, performance status and stage appeared to be independent variables in the choice of curative or symptomatic treatment.Age alone is not therefore a limiting factor in the choice of treatment.

Background A phase II trial of alternating i.v. and oral vinorelbine in combination with cisplatin was designed to determine the response rate, safety profile, progression-free survival, overall survival and quality of life (QoL) in advanced non-small-cell lung cancer (NSCLC). Patients and methods Fifty-six chemotherapy-naive patients received cisplatin 100 mg/m2 and i.v. vinorelbine 25 mg/m2 on day 1, followed by oral vinorelbine 60 mg/m2 on days 8, 15 and 22, every 28 days. Results After an independent review, the response rate was 33% [95% confidence interval (CI) 20% to 46%]. Median progression-free and overall survival were 5.5 months (95% CI 3.7–6.4) and 8.9 months (95% CI 8.8–11.7), respectively. The most frequent hematological toxicities were neutropenia (grade 3–4 in 73% of patients) and anemia (grade 3–4 in 11% of patients). Grade 3–4 infections and non-hematological toxicities occurred occasionally. QoL for lung cancer related symptoms was stable or improved. Conclusions The efficacy and safety of the alternating vinorelbine schedule (i.v. on day 1, oral on days 8, 15 and 22) in combination with cisplatin in advanced NSCLC are similar to those of the standard regimen using exclusively i.v. vinorelbine, whereas ease of administration and patient comfort may favor the novel approach.

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.

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.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.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.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.

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.

Breton Roland J.L. Berdichevsky N., The German-Danish Border: A Successful Resolution of an Age Old Conflict or its Redifinition?. In: Annales de Geographie, t. 110, n°619, 2001. p. 324.

Desulfovibrio africanus ferredoxin III (Da FdIII) contains one [4Fe-4S](2+/1+) cluster and one [3Fe-4S](1+/0) cluster, bound by seven Cys residues, in which the [3Fe-4S] cluster is co-ordinated by the unusual sequence, Cys(11)-Xaa-Xaa-Asp(14)-Xaa-Xaa-Cys(17)-Xaa(n)-Cys(51)-Glu. The [3Fe-4S] core of this ferredoxin is so far unique in showing rapid bi-directional [3Fe-4S][4Fe-4S] cluster interconversion with a wide range of metal ions. In order to obtain protein for mutagenesis studies Da FdIII has been cloned, sequenced, and expressed as a hexa-histidine tagged (ht) polypeptide in Escherichia coli strain BL21(DE3) pLysS. Expression of ht Da FdIII, whether translated from a synthetic gene (pJB10) or from the native nucleotide sequence (pJB11), occurred at similar levels (approx. 6 mg.l(-1)), but without incorporation of metal clusters. The nucleotide sequence confirms the protein sequence reported previously [Bovier-Lapierre, Bruschi, Bonicel and Hatchikian (1987) Biochim. Biophys. Acta 913, 20-26]. Cluster incorporation was achieved using FeCl(3) together with cysteine sulphur transferase, NifS, plus cysteine to generate low levels of sulphide ions. Absorption and EPR spectroscopy show that both [3Fe-4S] and [4Fe-4S] clusters are correctly inserted. Thin-film electrochemistry provides evidence that the [3Fe-4S] cluster undergoes reversible cluster transformation in the presence of Fe(II) and Zn(II) ions with properties identical to the native protein. Nevertheless the protein has lower stability than native Da FdIII during chromatography. The one-dimensional 600 MHz NMR spectrum of the apoprotein indicates an unstructured protein with random coil chemical shifts whereas spectra of the reconstituted ht protein show secondary structural elements and 18 peaks shifted downfield of 9.6 p.p.m. The spectra are unique but have similarities with the shift patterns seen with 7Fe Desulfurolobus ambivalens Fd. The ht does not affect iron-sulphur cluster incorporation, but NMR evidence suggests that excess Fe binds to the tag. This may account for the lower stability of the ht compared with the native protein.

The authors report a new case of bronchio-alveolar carcinoma which developed on a background of iatrogenic exogenous lipid pneumonia; this association is extremely rare (less than 20 cases in the literature) and poses the problem of possible cancer developing in the centre of the lipid pneumonia.

Nocardia farcinica, isolated by Nocard in 1888, has recently been redefined as a separate species to asteroides and has been recognised as human pathogen since 1975. Following airborne contamination, lung infection is most usual with frequent dissemination especially to central nervous system. Usually drug resistance makes treatment difficult. The authors describe the first case of Nocardia farcinica disseminated infection in France with lung primarily affection, empyema and encephalitis.

In a 62-year old man who consulted for dyspnoea, clinical, radiological and functional examinations led to the diagnosis of immunoallergic lung disease caused by gold salt therapy. Regression of the symptoms when gold salt therapy was withdrawn supported this diagnosis. Contrary to previously published cases concerning treatment with gold salts, the study of bronchoalveolar lavage (BAL) fluid yielded a lymphocytic alveolitis with a very high CD4/CD8 ratio, as already reported with methotrexate, cyclothiazide and nitrofurantoin. This case can be added to the list of drugs that may induce CD4 alveolitis; it also reminds the existence of gold salt pneumonia and permits to discuss the value of a lymphocyte subpopulation study in the BAL fluid in patients with drug-induced immunoallergic lung diseases.

The advent of fibroscopy, between 1865 and 1970, has made it possible to extend endoscopic exploration to high risk subjects, irrespective of their radiological image. We studied the initial radiological images observed on the standard film of 250 consecutive patients and compared these images with those observed and published by Emerson, Bariety and the Mayo Clinic 1970. The frequency of hilar mass (38%), peripheral tumours more than 4 cm in diameter (16%) and such pulmonary alterations as atelectasis or non-specific pneumonia (23.6%) has remained unchanged during the last decades. Similarly, the frequency of lung carcinomas discovered before they produced a radiological image is still low (2.8%).

The authors report a new case of menstrual pneumothorax and pelvic endometriosis which was discovered at this time. In this case (because of the presence of lesions suggesting the condition on thoracotomy) the probable mechanism thought to cause this pneumothorax would be the cyclical shedding of pleural endometriotic lesions. The authors review the characteristics of this unusual syndrome and base their review on an analysis of the hundred cases reported in the literature. They show that there are two theories of pathogenicity classically held. The first is the existence of congenital gaps in the diaphragm which allow air to pass into the pleura during the periods, the other is the possibility of endometriotic pleural lesions damaging the cortex of the lung as they shed their cells during the period.

7139 Background: Pts with NSCLC who progress on or after 1st line therapy but continue to have a good performance status (PS) may be offered 2nd line chemotherapy. VFL (Javlor) is a novel fluorinated vinca-alkaloid derivative synthesised using superacidic chemistry which has shown high activity in experimental tumour models. Methods: The aim of this trial was to determine the response rate and safety of VFL (320 mg/m2 q 3 weeks) as a single agent in pts with advanced NSCLC, who failed to a previous platinum-based regimen. Results: Sixty-three pts have been treated, 47 males, 16 females, median (m) age 60 years; Karnofsky PS 100 %: 14 pts, 90 %: 21 pts and 80 %: 28 pts. Prior platinum combinations included taxanes (31 % pts), vincas (31 % pts) and other (38 % pts). The total number of cycles administered was 221 (m: 5 [1 - 9]). Of the 62 evaluable pts, 38 (61 %, [95 % CI: 49–73 %]) achieved disease control: 5 pts (8 %, [95 % CI: 1–15 %]) partial response (independent radiological review) lasting 5.8 months...

Neo-adjuvant chemotherapy is a promising new concept in the treatment of resemble NSCLC. In 1991, a randomized study was initiated to compare two treatment strategies for patients (pts) with operable stages I (except T1N0), II or IIIa NSCLC. Pts are randomized into two arms. Surgery is performed first in group I. In group 2, pts start with two cycles of chemotherapy; following surgery, two more cycles are administered in responder pts. Chemotherapy is the MIP protocol: mitomycin 6 mg/m 2 day 1, ifosfamide 1.5 g/m 2 days 1 to 3, cisplatin 30 mg/m 2 days 1 to 3. In both groups, if the surgical staging is N2 or T3, a radiotherapy is performed. From June 1991 until Jan. 1995, 256 pts have been randomized; 35% are stage I, 16% are stage II. 205 pts have completed the treatment. In group 1, 105 out of 106 and in group 2, 91 out of 99 pts underwent thoracotomy. Surgery was complete in 85% of group 1, 83% of group 2, incomplete in 10% of group 1, 5% of group 2. The chemotherapy response rate assessed by surgical evaluation was as follow: complete and subcomplete response. 27%, 18%, partial response 31% (overall: 58%). The study is still ongoing as a total number of 350 patients should be included to reach the required power.

Breton Roland. — Religion and demographic change in India. This study of demographic change in India over a century of detailed censuses, shows characteristic behaviour in each socio-religious community, although within the context of its own traditions, and susceptible to more or less rapid change. For example, the highest growth rates at the time of the British Raj, were recorded among Christians, but since independence, birth rates among them have clearly begun to fall, much as in the West. Other communities have tended, each in its own fashion, towards slower growth, but much more gradually, notably the Moslems. The transition of India towards a regime of increasively controlled fertility has occurred at very different rates in different religious groups and provinces., Breton Roland. — Religion et évolution démographique en Inde. L'étude, à travers un siècle de recensements détaillés, de l'évolution des populations de l'Inde montre que chaque communauté socio-confessionnelle a eu, dans le cadre de ses traditions propres, un comportement démographique particulier, mais susceptible de changements plus ou moins rapides. Ainsi les Chrétiens, après avoir à l'époque britannique connu les accroissements les plus forts, ont, depuis l'indépendance, manifesté, au contraire, la tendance la plus nette et la plus brusque au ralentissement, à l'image des sociétés occidentales. Les autres communautés témoignent, chacune à sa façon, d'un ralentissement de leur croissance, mais beaucoup plus graduel, notamment chez les Musulmans. Ainsi s'esquisse, avec de considérables différences de rythme, suivant les groupes religieux et les provinces le passage de l'Inde à un régime général de natalité de plus en plus contrôlée., Breton Roland. — Religion y evolución demográfica en India. El estudio, a travès de un siglo de censos detallados, de la evolución de las poblaciones de la India muestra que cada comunidad socio-confesional ha tenido, en el marco de sus propias tradiciones, un comportamiento demográfico particular, pero susceptible de cambios más o menos rápidos. Asi los cristianos, tras haber conocido en el periodo británico el más fuerte crecimiento, desde la independencia han manifestado, рог el contrario, la más clara y brusca tendencia a la disminución, a imagen de las sociedades occidentales. Las otřas comunidades muestran, cada una a su manera, una disminución de su crecimiento, pero mucho más gradual, sobre todo entre los musulmanes. Asi se présenta el panorama, con considerables diferencias de ritmo, segûn los grupos religiosos y las provincias, de la evolución de la India hacia pautas de natalidad cada vez más controlada., Breton Roland. Religion et évolution démographique en Inde. In: Population, 43ᵉ année, n°6, 1988. pp. 1089-1122.

We report on the construction of a 10-mm bore 60-W continuous wave argon ion laser operated at a discharge power of about 64 kW, which provides a continuous current of 200 A. Specially designed high-current-density anodes and cathodes are described. Experimental results on the effects of an axial magnetic field (0–875 G) on discharge parameters are also presented.

Breton Roland. — Ethnic Groups in the Soviet Union. Soviet statistics record the nationality of each citizen, as well as his or her mother tongue and the second language spoken. These statistics are published in the Census of Population and provide a better picture of the division of the Soviet population into nationalities and of the vitality of these nationalities than do the statistics of population classified by constituent Republics. Differences between European and Asian ethnic groups are becoming more pronounced. Except in Europe, the populations of ethnic Russians are everywhere diminishing in importance. Knowledge of the vernacular languages, which has been encouraged since the time that the constituent Republics were founded, is widespread, except among some smaller nationalities and some populations of foreign origin (Germans, Poles, Koreans). Knowledge of the Russian language which is an important unifying factor is also rapidly increasing. In many of the constituent Republics, the Russian language is already understood by more than half of the population., Breton Roland. — L'évolution des ethnies soviétiques. Les statistiques soviétiques recensent chaque citoyen selon sa nationalité, sa langue maternelle, et la seconde langue parlée. Ces données sont publiées lors des recensements et permettent de se faire une idée de la répartition des nationalités et de leur dynamisme, idée plus exacte que pour les données classées par République. La différence entre ethnies européennes et asiatiques est plus nette encore. Partout sauf en Europe, les populations russes voient leur représentation diminuer. Les langues maternelles encouragées dès les débuts de la République sont en pleine vitalité à l'exception de petites nationalités ou de nationalités étrangères (allemands, polonais, coréens). Seul facteur d'unification, la langue russe se répand assez rapidement comme deuxième langue. Elle est déjà comprise par plus de la moitié de la population dans de nombreuses républiques., Breton Roland. — Evolución de la población soviética según características étnicas. Los censos soviéticos recopilan la nacionalidad, lengua materna y secunda lengua hablada рог cada ciudadano. Sobre la base de estos datos puede estudiarse la evolución de la población según nacionalidades de una manera más satisfacto- ria que a partir de la repartición de la población рог Repúblicas. Se nota mejor la diferencia entre étnias europeas y asiáticas. La proporción de poblaciones rusas disminuyen en todas las regiones, salvo en Europa. Las lenguas maternas, que fueron estimuladas desde el comienzo de la República, se mantienen en plena vitalidad con la exception de las correspOndientes a las nacionalidades más pequefias о a las nacionalidades extranjeras (alemana, polaca, coreana). La lengua rusa se extiende rapidamente como una segunda lengua y constituye un factor único de unification. Actualmente es comprendida por más de la mitad de la población de numerosas repúblicas., Breton Roland. L'évolution des ethnies soviétiques. In: Population, 38ᵉ année, n°1, 1983. pp. 61-76.

We report on a novel technique for generating large area flowing sheets of viscous fluids for use in dye lasers. The proposed technique allows one to control the shape, size and thickness of the fluid sheets of excellent optical quality. Rhodamine 6G/ethylene glycol jet streams have been investigated. Application to other dye/solvents, to saturable absorbers or to other fluids is straightforward.

The authors present a case of Abrikossoff's tumor located in the segmental bronchus and detected on a systematic chest radiography, diagnosed during an endoscopy is reported. The CT study specified the tumoral extension. Bronchial distal affections is very rare. A confrontation with the anatomopathological data allowed a better understanding scanographic aspect.

The authors report a case of Wegener's granulomatosis, whose initial manifestation was an isolated endobronchial stenosis. In connection with this observation, it calls to mind, within the scope of the pulmonary granulomas (in view of such a rare clinical presentation) the difficulties of differential diagnosis, in particular with bronchocentric granulomatosis, and stresses the need for pulmonary histological examination to open lung biopsy.

The authors report two new cases of menstrual pneumothorax. In both cases the lesions of endometriosis seemed to dominate the pathogenesis. After a rapid review of the literature to elucidate the main clinical characteristics of this curious syndrome, the authors stress the advantage of a pleuroscopic examination in women with the syndrome.

The authors report three cases of endothoracic tumour recurrence in patients who have been operated on for primary lung cancer revealed by CT scanning, carried out systematically in the respiratory unit to a pre-established protocol. There were no other clinical, fibre-optic, or radiological signs of these recurrences before their discovery using CT scanning. The authors discuss the value of thoracic scanning in the systematic follow up of operated cases of bronchial cancer.