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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.

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.

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.

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.

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 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.

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.

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 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.