Jean Tredaniel

Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial.

BACKGROUND Platinum-based doublet chemotherapy is recommended to treat advanced non-small-cell lung cancer (NSCLC) in fit, non-elderly adults, but monotherapy is recommended for patients older than 70 years. We compared a carboplatin and paclitaxel doublet chemotherapy regimen with monotherapy in elderly patients with advanced NSCLC. METHODS In this multicentre, open-label, phase 3, randomised trial we recruited patients aged 70-89 years with locally advanced or metastatic NSCLC and WHO performance status scores of 0-2. Patients received either four cycles (3 weeks on treatment, 1 week off treatment) of carboplatin (on day 1) plus paclitaxel (on days 1, 8, and 15) or five cycles (2 weeks on treatment, 1 week off treatment) of vinorelbine or gemcitabine monotherapy. Randomisation was done centrally with the minimisation method. The primary endpoint was overall survival, and analysis was done by intention to treat. This trial is registered, number NCT00298415. FINDINGS 451 patients were enrolled. 226 were randomly assigned monotherapy and 225 doublet chemotherapy. Median age was 77 years and median follow-up was 30.3 months (range 8.6-45.2). Median overall survival was 10.3 months for doublet chemotherapy and 6.2 months for monotherapy (hazard ratio 0.64, 95% CI 0.52-0.78; p<0.0001); 1-year survival was 44.5% (95% CI 37.9-50.9) and 25.4% (19.9-31.3), respectively. Toxic effects were more frequent in the doublet chemotherapy group than in the monotherapy group (most frequent, decreased neutrophil count (108 [48.4%] vs 28 [12.4%]; asthenia 23 [10.3%] vs 13 [5.8%]). INTERPRETATION Despite increased toxic effects, platinum-based doublet chemotherapy was associated with survival benefits compared with vinorelbine or gemcitabine monotherapy in elderly patients with NSCLC. We feel that the current treatment paradigm for these patients should be reconsidered. FUNDING Intergroupe Francophone de Cancérologie Thoracique, Institut National du Cancer.

Tobacco smoking and gastric cancer: Review and meta-analysis

Although declining, gastric cancer (GC) is estimated to be second in frequency worldwide. Major causes appear to be environmental rather than genetic. A relationship has been suggested between tobacco smoking and GC. A number of epidemiological studies have been performed dealing with this question. All the cohort studies showed a significantly increased risk of GC of the order of 1.5–2.5 for cigarette smokers. Evidence from case‐control studies is less consistent. We have carried out a meta‐analysis on the 40 studies providing a quantitative estimate of the association between GC risk and tobacco smoking. Results suggest a risk of stomach cancer among smokers of the order of 1.5–1.6 as compared to non‐smokers. The summary relative risk was higher in men (1.59) than in women (1.11). Several studies examined the dose‐response relationship which existed in 4 cohort studies and 6 case‐control studies. We estimated the number of GC cases attributable to tobacco smoking occurring worldwide: in total, over 80,000 cases of GC (11% of all estimated cases) may be attributed to tobacco smoking each year. This figure is larger than that estimated for other cancers for which association with tobacco smoking is clearly established, such as pancreatic and renal cancers. Int. J. Cancer 72:565–573, 1997.

Bevacizumab in Patients with Nonsquamous Non–Small Cell Lung Cancer and Asymptomatic, Untreated Brain Metastases (BRAIN): A Nonrandomized, Phase II Study

Purpose: The phase II prospective, noncomparative BRAIN study (NCT00800202) investigated efficacy and safety of bevacizumab in chemotherapy-naïve or pretreated patients with non–small cell lung cancer (NSCLC) and asymptomatic untreated brain metastases to provide data in this previously unexplored subgroup. Experimental Design: Patients with stage IV nonsquamous NSCLC, Eastern Cooperative Oncology Group performance status 0–1, and untreated, asymptomatic brain metastases received first-line bevacizumab (15 mg/kg) plus carboplatin (area under the curve ×6) and paclitaxel (200 mg/m2) every 3 weeks (B + CP), or second-line bevacizumab plus erlotinib (150 mg/d; B + E). Six-month progression-free survival (PFS) was the primary endpoint. The trial could be stopped if there were more than three (B + CP) or more than two (B + E) intracranial hemorrhages. Results: In first-line B + CP cohort (n = 67), 6-month PFS rate was 56.5% with a median PFS of 6.7 months [95% confidence interval (CI), 5.7–7.1] and median overall survival (OS) of 16.0 months. Investigator-assessed overall response rate (ORR) was 62.7%: 61.2% in intracranial lesions and 64.2% in extracranial lesions. Because of low enrolment (n = 24), efficacy results for the second-line B + E cohort were exploratory only; 6-month PFS rate was 57.2%, median PFS was 6.3 months (95% CI, 3.0–8.4), median OS was 12.0 months, and ORR was 12.5%. Adverse events were comparable with previous trials of bevacizumab. One grade 1 intracranial hemorrhage occurred and resolved without sequelae. Conclusions: The BRAIN study demonstrates encouraging efficacy and acceptable safety of bevacizumab with first-line paclitaxel and carboplatin in patients with NSCLC and asymptomatic, untreated brain metastases. Clin Cancer Res; 21(8); 1896–903. ©2015 AACR.

Exposure to environmental tobacco smoke and adult non-neoplastic respiratory diseases

Exposure to environmental tobacco smoke (ETS) is widespread in European countries, the most serious exposures occurring at home and in the workplace. Epidemiological studies have, essentially, addressed the association between ETS exposure and respiratory health in children, and increased risk of lung cancer among adult nonsmokers. Relatively few studies have been reported on ETS and adult non-neoplastic respiratory diseases. On the basis of the available data, no definite conclusion (excluding the acute irritating effect of ETS on respiratory mucous membranes) can be drawn. Although biologically plausible, it remains controversial whether ETS exposure is associated with chronic respiratory symptoms and occurrence of chronic obstructive pulmonary disease, including asthma. Most of the studies that have used the most sensitive indicators of pulmonary function have suggested a negative impact of ETS exposure. However, if really present, the physiological significance of such small changes is unclear, and the relationship to long-term changes in lung function is not established. Moreover, the possibility of bias and confounding factors must be taken into account. Thus, there is a need for further epidemiological studies on ETS exposure and adult non-neoplastic respiratory disorders.

Predictive factors for late toxicity after endobronchial brachytherapy: a multivariate analysis

PURPOSE To determine the predictive factors associated with hemoptysis and radiation bronchitis after endobronchial brachytherapy by univariate and multivariate analyses METHODS AND MATERIALS One hundred forty-nine patients underwent endobronchial brachytherapy and were divided into three therapeutic groups: group 1: patients treated with palliative intent (n=47); group 2: patients treated with curative intent (small endobronchial tumors without mediastinal or general dissemination: n=73); group 3: patients also receiving external irradiation (n=29). One hundred twelve patients had previously received external irradiation. Brachytherapy was delivered with a dose per fraction ranging from 4 to 7 Gy and a prescription point between 0.5 and 1.5 cm, usually 1 cm from the source center. Two to six fractions were delivered according to the therapeutic group and clinical situation. The influence of the following variables on the incidence of hemoptysis or radiation bronchitis was studied: age, sex, Karnofsky score, therapeutic group, histologic type, endoscopic tumor length, dose per fraction, total brachytherapy dose, total external beam irradiation dose, total dose (brachytherapy dose plus external irradiation dose), volumes of the 100% and 200% isodoses, and volumes of the 7 and 14 Gy isodoses. RESULTS We observed 11 hemoptyses (7.4%), 10 were lethal. All but one occurred in patients with progressive disease. Two clinical factors were significantly associated with hemoptysis by univariate analysis: palliative group (p=0.009) and endobronchial tumor length (p=0.004). No technical factors seem to be implicated in the occurrence of hemoptysis. Only endobronchial tumor length remained in the multivariate model (p=0.02). Radiation bronchitis was observed in 13 cases (8.7%). By univariate analysis, a good Karnofsky score (p=0.02), curative treatment (p=0.02), and tumor location on trachea and main stem bronchus (p=0.002) were significantly associated with this complication. Two technical factors were also incriminated: the total dose (p=0.04) and the 100% isodose volume (p=0.02). By multivariate analysis, only the tumor location retained statistical significance (p=0.009). CONCLUSION Hemoptysis is most likely due to disease progression, with the bleeding being facilitated by brachytherapy. Some rare cases could be a direct complication of brachytherapy itself, particularly when tumors are located in the upper lobes. In contrast, radiation bronchitis occurred more frequently in patients with controlled disease, and was significantly influenced by tumor location and technical factors (dose and volumes treated). Technical improvements should increase the therapeutic ratio.

Exposure to environmental tobacco smoke and risk of lung cancer: the epidemiological evidence

Exposure of nonsmokers to environmental tobacco smoke (ETS) is widespread in European countries, the most serious exposures occurring at home and in the workplace. Epidemiological studies available up to 1986 have been reviewed by several international and national authorities, which agreed in concluding that ETS exposure is causally related to lung cancer. A number of epidemiological studies have been published since then, and have confirmed this association. The possibility of positive results due to bias has been envisaged; it seems, however, that such bias could not explain the whole excess of lung cancer. Few data are available on confounders, such as diet and previous history of lung disease, that might be responsible for the association; however, there is no evidence that they play an important role. Moreover, the biological plausibility of a causal association is supported by the similarity of the composition of ETS and active smoke. The causal association between ETS exposure and lung cancer now seems well-established; however, its public health impact is still debated. Estimates are available from the United States, Canada, Australia, New Zealand and England.

Prognostic significance of serum p53 antibodies in patients with limited‐stage small cell lung cancer

p53 tumour suppressor gene alterations are one of the most frequent genetic events in lung cancer. A subset of patients with p53 mutation and cancer exhibited circulating serum anti‐p53 self‐antibodies (p53‐Ab). The prevalence of these antibodies in lung cancer is currently being analysed in a multicentric study. In a group of homogeneous SCLC patients, p53‐Ab were detected in 20/97 (20.6%) individuals. In this group of patients, Coxs multivariate analysis identified disease extent (p = 0.022), WHO initial performance status greater than 0 (p = 0.005), and the absence of a complete response after 6 months of treatment (p < 0.0001) as independent prognostic variables, with p53‐Ab being of borderline significance (p = 0.051). In the subset of limited‐stage SCLC patients, Coxs multivariate analysis found p53‐Ab (p = 0.033), WHO initial performance status greater than 0 (p = 0.028), and absence of a complete response (p < 0.001) to be independent prognostic variables. Thus, actuarial analysis showed that patients with limited‐stage SCLC and p53‐Ab had a median survival time of 10 months, whereas limited‐stage SCLC patients without p53‐Ab had a 17‐month median survival time (p = 0.014).Therefore, serum assay of p53‐Ab could help to identify a population of SCLC patients with an especially poor prognosis. This population could represent patients with tumours harboring aggressive p53 mutations. Int. J. Cancer (Pred. Oncol.) 89:81–86, 2000.

Environmental tobacco smoke and the risk of cancer in adults

The apparent effect of environmental tobacco smoke (ETS) exposure on cancer risk has become an important social and political issue. The risk of cancer in non-smokers is often the main reason for prohibiting or restricting smoking in public places. A number of epidemiological studies have shown an association between ETS exposure and lung cancer. However, the strength of this association has still to be estimated. Only a few studies have reported on ETS and cancer from sites other than the lung in adults. No definite conclusions can be drawn at present from a critical review of the epidemiological evidence, but the suggestion of an association is present for sinonasal cancer, while bladder cancer does not seem to be associated to ETS exposure. Positive studies are available for cancers from other sites, including the breast, the uterine cervix and the brain, but these are difficult to interpret.

Protocole IFCT-0302 : essai randomisé de deux schémas de surveillance dans les cancers bronchiques non à petites cellules complètement réséqués

Resume Etats des connaissances Les instances scientifiques preconisent une attitude minimaliste dans la surveillance des cancers bronchiques operes (examen clinique et radiographie thoracique). D’apres une enquete, 70 % des pneumologues francais ont opte pour l’usage du scanner et souvent de l’endoscopie. Les donnees de la litterature sont disparates, souvent issues d’etudes retrospectives. Methodes Le cancer bronchique est un bon modele pour realiser un essai de surveillance postoperatoire. Les recidives surviennent frequemment dans une aire facile a surveiller, peuvent etre decouvertes alors qu’elles sont encore asymptomatiques, sont parfois accessibles a un traitement curatif, ont un siege identique a celui des 2 e cancers observes. L’Intergroupe Francophone de Cancerologie Thoracique (IFCT) a debute un essai comparant une surveillance legere (examen clinique, radiographie thoracique) a une surveillance lourde (scanner, fibroscopie). La surveillance est realisee tous les 6 mois pendant 2 ans puis annuellement jusqu’a 5 ans. Resultats attendus L’objectif principal est de savoir si une surveillance lourde permet d’augmenter la survie des patients. Toute aussi importante est la question inverse. Si une surveillance couteuse et penible n’interfere pas sur les chances de guerison, il est fondamental d’en tirer les consequences sur les pratiques.

Pollution atmosphérique et cancer bronchique : données épidémiologiques

Introduction Une litterature abondante a ete consacree aux effets a court terme de la pollution sur la sante humaine, mais peu de donnees sont disponibles sur les effets a long terme tels que la survenue d’un cancer bronchique. Etat des connaissances Les effets sur la mortalite par cancer du poumon ont ete evalues dans le cadre de 6 etudes prospectives de cohorte, 3 americaines et 3 europeennes. Ces travaux mettent en evidence, de facon coherente, une association entre l’exposition aux polluants ambiants et des taux eleves de mortalite cardio-pulmonaire et par cancer bronchique. Ce sont essentiellement les particules emises par les moteurs diesel qui sont en cause. Perspectives Bien que le risque a l’echelon individuel puisse sembler relativement modere s’il est compare a celui lie a la consommation tabagique, les consequences a l’echelle de la population, dont tous les membres sont plus ou moins exposes a la pollution, ne peuvent etre negligees. Conclusion Ces elements justifient la poursuite des travaux sur ce theme.