Antiangiogenic Agents and Vascular Disrupting Agents for the Treatment of Lung Cancer: A Review

AbstractAlthough lung cancer therapy has slowly improved with standard cytotoxic chemotherapy drugs, we have reached an efficacy plateau. The addition of targeted agents, such as those with antiangiogenesis activity, to chemotherapy can improve response and survival outcomes. The first of these agents to gain approval in lung cancer in October 2006 was the antivascular endothelial growth factor antibody, bevacizumab. Small molecule tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptor also have proven activity and are under active investigation. Vascular disrupting agents target existing tumor vasculature leading to tumor necrosis, and are being studied in solid tumors, including lung cancer, both as single agents and in combination with chemotherapy. This article will review these new targeted antiangiogenic and antivascular agents with a focus on their use as lung cancer therapeutics

Quality of life after the initial treatments of non-small cell lung cancer: a persistent predictor for patients' survival.

International audienceBACKGROUND: Health-related quality of life (HRQoL) before treatment may predict survival of patients with non-small-cell lung cancer (NSCLC). We investigated the predictive role of HRQoL after the initial treatments, on the survival of these patients. METHODS: A prospective multi-center study conducted in northeastern France. The SF-36 and European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (QLQ C-30) were mailed to patients 3 months after the end of the diagnostic process. High scores for functioning dimensions on both questionnaires indicated better QoL, and low scores for symptom dimensions on the QLQ C-30 indicated few symptoms. Cox regression modeling was used to identify predictive factors of survival. RESULTS: In total, 230 (63.5%) patients responded to the SF-36 and QLQ C-30. Before completing the questionnaires, almost 60% of patients had undergone some chemotherapy, about 10% underwent radio/chemotherapy or both and more than 30% underwent surgery or surgery plus chemo/radiotherapy.On SF-36, the highest mean score was for social functioning dimension (55.5 ± 28), and the lowest was for the physical role dimension (17.9 ± 32.2).On QLQ C-30, for the functioning dimensions, the highest mean score was for cognitive functioning (74.6 ± 25.9) and the lowest was for role functioning (47.2 ± 34.1). For symptom dimensions, the lowest score was for diarrhoea (11.5 ± 24.2) and the highest was for fatigue (59.7 ± 27.7).On multivariate analysis, high bodily pain, social functioning and general health scores (SF-36) were associated with a lower risk of death (hazard ratio 0.580; 95% confidence interval [0.400-0.840], p = 0.004; HR 0.652 [0.455-0.935], p < 0.02; HR 0.625 [0.437-0.895] respectively). Better general QoL on QLQ C-30 was related to lower risk of death (HR 0.689 [0.501-0.946], p = 0.02). CONCLUSION: Adding to previous knowledge about factors that may influence patients QoL, this study shows a persisting relationship between better perceived health in HRQoL after the initial treatment of NSCLC and better survival

Cancer bronchique et facteurs de risque : Existe-t-il des marqueurs phénotypiques spécifiques ?

Lung cancer is the leading cause of death in the world. Most lung cancer are diagnosed at an advanced stage (IIIB and IV), with a poor prognosis. The main risk factors are well known like active smoking, and occupational exposure (asbestos), but 10 à 20% occur in never smokers. In this population, various studies have been conducted in order to identify possible risk factors, and although many have been identified, none seem to explain more than a small percentage of the cases. According to the histological types, adenocarcinoma is now the more frequent type, and its association with the main risk factors (tobacco exposure, asbestos exposure) is still studied. The tumoral location is associated with the exposure to the risk factors. Finally, the survival seems to be different between gender, and between smokers, and never smokers. All these characteristics are perhaps associated with different pathways of carcinogenesis. In this context, we have analyzed a cohort of 1493 patients with lung cancer in order to identify phenotypic markers, and to understand the mechanisms of the lung carcinogenesis.Le cancer bronchique est la première cause de mortalité par cancer dans le monde, en raison d'un diagnostic à un stade avancé (IIIB et IV) et d'un pronostic sombre. Si les principaux facteurs de risques sont connus depuis de nombreuses décennies comme le tabagisme actif et les expositions professionnelles (amiante), 10 à 20 % de patients sont des non-fumeurs. Dans cette population, les étiologies restent plus controversées. Au niveau histologique, l'adénocarcinome est devenu le type histologique le plus fréquent et son association avec les facteurs de risque (tabagisme, exposition à l'amiante) fait débat. De même, la localisation tumorale est différente selon l'exposition aux différents facteurs de risque. Enfin, la survie du cancer bronchique semble être différente selon le sexe ou le statut tabagique. Suivant les expositions et les populations, les mécanismes de carcinogénèse diffèrent. C'est dans ce contexte, que notre étude a été menée sur une cohorte de 1493 patients atteints de cancer bronchique afin d'identifier des populations à risque et de mieux comprendre les voies de la carcinogénèse bronchique

Benign metastasizing leiomyoma with lung cystic lesions and pneumothoraces: A case report

AbstractBenign metastasizing leiomyoma (BML) affects women of the middle age, and is a rare disease. Typically, in BML, uterine leiomyoma, and lung nodes are found. In the literature, only 3 cases of large cysts have been reported. In our case, we describe a patient with uterine leiomyoma with lung cysts, and several pneumothoraces

Radiothérapie stéréotaxique hypofractionnée des métastases cérébrales : bénéfice de l’irradiation encéphalique totale ?

International audiencePurpose: To study overall survival, risk of neurological death, local recurrence and development of new brain metastasis in patients treated for brain oligometastases with hypofractionated stereotactic radiotherapy with CyberKnife®, according to the association or not with an additional whole brain irradiation.Patients and methods: Institutional retrospective study of 102 patients treated for one to three brain metastasis: 76 with exclusive hypofractionated stereotactic radiotherapy and 26 with hypofractionated stereotactic radiotherapy and whole brain irradiation. Objectives were assessed and compared between these two groups according to the Kaplan–Meier method and Cox model.Results: Median follow-up was 18.8 months. There were no difference between exclusive hypofractionated stereotactic radiotherapy and hypofractionated stereotactic radiotherapy with whole brain irradiation for overall survival (respective median 21.5 and 20.1 months), risk of neurological death (respectively 9.2% and 15.4% at one year). At one year: the risk of cerebral progressive disease was greater in the group receiving exclusive hypofractionated stereotactic radiotherapy (respectively 43.4% vs. 26.2%, P = 0.043), the risk of local recurrence was 25% versus 17.6% (P = 0.28) and the development of new brain metastasis was 23.7% versus 11.5% (P = 0.27). After salvage treatments, crude local control was similar in the two groups, respectively 78.6% and 73.5%. Whole brain irradiation has been avoided for 72.4% of patients in the group receving exclusive hypofractionated stereotactic radiotherapy.Conclusion: Whole brain irradiation improves local control of brain metastatic disease in addition to hypofractionated stereotactic radiotherapy. Sparing whole brain irradiation for salvage treatments only does not affect overall survival or risk of neurological death in selected patients with favourable prognosis.Objectifs: Étude de la survie globale, du risque de décès neurologique, de la progression locale et de l’apparition de nouvelles métastases cérébrales chez des patients pris en charge pour des oligométastases cérébrales par irradiation stéréotaxique hypofractionnée par CyberKnife®, selon l’association ou non à une irradiation encéphalique totale complémentaire.Patients et méthodes: Étude rétrospective institutionnelle sur 102 patients pris en charge pour une à trois métastases cérébrales : 76 par irradiation stéréotaxique hypofractionnée exclusive et 26 par irradiation stéréotaxique hypofractionnée et irradiation encéphalique totale. Les objectifs ont été évalués et comparés entre ces deux groupes selon la méthode de Kaplan–Meier et le modèle de Cox.Résultats: Le suivi médian était de 18,8 mois. Il n’y avait pas de différence entre les groupes traités par irradiation stéréotaxique hypofractionnée exclusive et ceux traités par irradiation stéréotaxique hypofractionnée et irradiation encéphalique totale en termes de survie globale (médianes respectives de 21,5 mois et 20,1 mois), ni de risque de décès neurologique (9,2 % et 15,4 % à un an). Le risque de progression cérébrale à un an était plus important dans le groupe traité par irradiation stéréotaxique hypofractionnée exclusive (43,4 % contre 26,2 %, p = 0,043), avec un risque de progression locale de 25 % contre 17,6 % (p = 0,28) et d’apparition de nouvelles métastases cérébrales de 23,7 % contre 11,5 % (p = 0,28). Après traitements de rattrapage, le taux de contrôle local brut était identique entre les deux groupes, respectivement 78,6 % et 73,5 %. La radiothérapie encéphalique totale a pu être évitée pour 72,4 % des patients du groupe traité par irradiation stéréotaxique hypofractionnée exclusive.Conclusion: L’irradiation encéphalique totale améliore le taux de contrôle local de la maladie métastatique cérébrale en complément de l’irradiation stéréotaxique hypofractionnée. Ne pas la réaliser d’emblée pour la réserver aux seuls traitements de rattrapage n’altère ni la survie globale ni le risque de décès neurologique chez les patients sélectionnés, atteints de cancer de pronostic favorable

Characteristics of never smoker lung cancer including environmental and occupational risk factors.

International audienceINTRODUCTION: Clinical characteristics and risk factors of nonsmoker patients with lung cancer are still debated. AIM AND METHODS: The aim of this work is to describe the characteristics of never smoker patients with lung cancer, focusing on occupational and environmental exposures, Data collected were: age, gender, histological types, methods of diagnosis, TNM staging, smoking, and occupational data. Statistical analysis included descriptive analyses, Pearson's chi-square or nonparametric tests, and logistic regressions. RESULTS: All lung cancers diagnosed between January 1, 1997 and December 31, 2006, representing 1493 cases were included. Lung adenocarcinoma (ADC) [Odds Ratio (OR)=2.5 (1.5-4.3), p<0.0001] as well as clinical stage I cases at diagnosis [OR=2.4 (1.3-4.3)] were most frequent in nonsmokers relative to ever smokers. Comparison of clinical features among male and female nonsmoker patients did not reveal significant differences. Conversely, strong differences appeared when comparing environmental tobacco smoke (ETS) and occupational exposures in nonsmoker women vs men: ETS exposure (78.6% nonsmoker women vs 21.4% nonsmoker men, p<0.0001), occupational exposure (9.4% vs 48.6%, p<0.0005). Noteworthy, a sizeable number of nonsmoker male (40.0%), and nonsmoker female (31.2%) patients had no known exposure to major lung carcinogens. CONCLUSIONS: Main risk factors (ETS and occupational exposure) may only explain some cases

How Accurate Are Physicians in the Prediction of Patient Survival in Advanced Lung Cancer?

The study compared actual with predicted survival estimates in advanced stage non-small cell lung cancer patients. Regardless of years of experience, physicians overestimated the survival duration of these patients

A Phase II First-Line Study of Gemcitabine, Carboplatin, and Bevacizumab in Advanced Stage Nonsquamous Non-small Cell Lung Cancer

Background:Bevacizumab improves responses and progression-free survival when added to first-line paclitaxel/carboplatin or cisplatin/gemcitabine for patients with advanced nonsquamous non-small cell lung cancer. This study was designed to evaluate toxicities and efficacy of gemcitabine/carboplatin/bevacizumab.Methods:Patients with untreated advanced nonsquamous non-small cell lung cancer, with no evidence of brain metastases and not on anticoagulation were eligible. Patients received gemcitabine 1000 mg/m2 on days 1 and 8; carboplatin area under the curve 5 day 1; and bevacizumab 15 mg/kg day 1 every 3 weeks for up to six cycles. Bevacizumab was then continued every 3 weeks until disease progression or unacceptable toxicity.Results:From July 2006 to December 2008, 48 patients were enrolled: 23 (48%) men, 25 (52%) women, and 19 (40%) never smokers. One patient never received therapy and is not included in the analysis. Median cycle number was 8 (1–42) with 37 patients (78.7%) completing ≥4 cycles of three drugs. Dose reductions occurred in 34 (72.3%) patients. Grade 3/4 toxicities included neutropenia (47%/15%), thrombocytopenia (11%/15%), anemia (6%/0%), dyspnea (6%/2%), bacterial pneumonia (4%/0%), and hypertension (4%/2%). No neutropenic fevers occurred. One patient died of hemoptysis. Grade 3 bleeding occurred in three other patients. There were seven (14.9%) partial responses. Median time to first event (progression/death/toxicity requiring discontinuation) was 6.4 months (95% confidence interval: 4.8–7.9 months). The median overall survival (OS) was 12.8 months (95% confidence interval: 10.0–16.5). The OS is 57% at 1 year and 10% at 2 years.Conclusions:Although perhaps skewed by a high proportion of nonsmokers and women, treatment with gemcitabine/carboplatin/bevacizumab has an acceptable toxicity profile with promising median OS despite a low response rate