[Management and outcome of French elderly patients with lung cancer: an IFCT survey]. / IFCT 02-02 : la prise en charge du cancer bronchique chez les patients âgés de 70 ans et plus en France.

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.

[IFCT-0302 trial: randomised study comparing two follow-up schedules in completely resected non-small cell lung cancer]. / Protocole IFCT-0302: essai randomisé de deux schémas de surveillance dans les cancers bronchiques non à petites cellules complètement réséqués.

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.

[Treatment of localised lung cancer]. / Traitement des cancers du poumon localisés au thorax.

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.

[Preoperative chemotherapy in non-small cell lung cancer: advantages, disadvantages, level of evidence]. / La chimiothérapie préopératoire dans les cancers bronchiques non à petites cellules : avantages, inconvénients, niveau de preuve.

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.

Long-duration, weekly treatment with gemcitabine plus vinorelbine for non-small cell lung cancer: a multicenter phase II study.

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.

[Early stages of non small cell lung cancer (I. II. IIIA). Role of preoperative treatments]. / CBNPC de stades précoces (I. II. IIIA). Place des traitements préopératoires.

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.

[Pain management in bone metastasis of pulmonary origin: new interventional and metabolic techniques]. / Nouvelles techniques interventionnelles et métaboliques dans la prise en charge des métastases osseuses.

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.

[Pre-operative chemotherapy in non-small cell lung cancer]. / La chimiothérapie préopératoire des cancers bronchiques non à petites cellules localisés.

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.

Gemcitabine-docetaxel versus cisplatin-vinorelbine in advanced or metastatic non-small-cell lung cancer: a phase III study addressing the case for cisplatin.

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.

[Pre- and peri-surgical chemotherapy of stage I and II resectable non-small cell lung cancers]. / La chimiothérapie préopératoire et périopératoire des cancers bronchiques non à petites cellules résécables de stades I et II.

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.

Multivariate analysis of factors predictive of brain metastases in localised non-small cell lung carcinoma.

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.

Randomised, multicentre phase II study assessing two doses of docetaxel (75 or 100 mg/m2) as second-line monotherapy for non-small-cell lung cancer.

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.

Respiratory status in dairy farmers in France; cross sectional and longitudinal analyses.

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.

Overview of the role of neoadjuvant chemotherapy for early stage non-small cell lung cancer.

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.

[Standards, Options and Recommendations for the management of stage I or II primary bronchial cancers treated exclusively with radiotherapy]. / Standards, Options et Recommandations pour la prise en charge des patients atteints d'un cancer bronchique primitif de stade I ou II traités par irradiation exclusive.

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.