Second-line therapy in elderly patients with advanced nonsmall cell lung cancer.

There is no dedicated study on second-line treatment for elderly patients with advanced nonsmall cell lung cancer (NSCLC). We report the results on second-line erlotinib therapy from our previously published phase III study comparing single-agent therapy with platinum-based doublet (carboplatin plus paclitaxel) therapy in 451 elderly patients. Erlotinib was given to patients exhibiting disease progression or experiencing excessive toxicity during first-line therapy, until further progression or unacceptable toxicity. In total, 292 (64.7%) patients received erlotinib as second-line therapy. Initial performance status 0-1, stage IV NSCLC and an Activities of Daily Living score of 6 were independent factors for receiving erlotinib. Median (95% CI) overall survival was 4 (3.2-6.7) versus 6.8 (5.0-8.3) months in the single-agent and doublet arms, respectively (p=0.089). Performance status 0-1, never having smoked, adenocarcinoma and weight loss ≤5% were favourable independent prognostic factors of survival, whereas the randomisation arm had no significant impact. Among the 292 patients who received erlotinib, 60 (20.5%) experienced grade 3-4 toxic effects, the most frequent being rash. Erlotinib as second-line therapy is feasible, leading to efficacy results similar to those obtained in a previous randomised study that was not dedicated to elderly patients, with acceptable toxicity.

Cost-utility analysis of maintenance therapy with gemcitabine or erlotinib vs observation with predefined second-line treatment after cisplatin-gemcitabine induction chemotherapy for advanced NSCLC: IFCT-GFPC 0502-Eco phase III study.

BACKGROUND: The IFCT-GFPC 0502 phase III study reported prolongation of progression-free survival with gemcitabine or erlotinib maintenance vs. observation after cisplatin-gemcitabine induction chemotherapy for advanced non-small-cell lung cancer (NSCLC). This analysis was undertaken to assess the incremental cost-effectiveness ratio (ICER) of these strategies for the global population and pre-specified subgroups. METHODS: A cost-utility analysis evaluated the ICER of gemcitabine or erlotinib maintenance therapy vs. observation, from randomization until the end of follow-up. Direct medical costs (including drugs, hospitalization, follow-up examinations, second-line treatments and palliative care) were prospectively collected per patient during the trial, until death, from the primary health-insurance provider's perspective. Utility data were extracted from literature. Sensitivity analyses were conducted. RESULTS: The ICERs for gemcitabine or erlotinib maintenance therapy were respectively 76,625 and 184,733 euros per quality-adjusted life year (QALY). Gemcitabine continuation maintenance therapy had a favourable ICER in patients with PS = 0 (52,213 €/QALY), in responders to induction chemotherapy (64,296 €/QALY), regardless of histology (adenocarcinoma, 62,292 €/QALY, non adenocarcinoma, 83,291 €/QALY). Erlotinib maintenance showed a favourable ICER in patients with PS = 0 (94,908 €/QALY), in patients with adenocarcinoma (97,160 €/QALY) and in patient with objective response to induction (101,186 €/QALY), but it is not cost-effective in patients with PS =1, in patients with non-adenocarcinoma or with stable disease after induction chemotherapy. CONCLUSION: Gemcitabine- or erlotinib-maintenance therapy had ICERs that varied as a function of histology, PS and response to first-line chemotherapy.

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.

[The non-surgical treatment of lung cancer]. / Le traitement non chirurgical du cancer du poumon.

Advances in the treatment of lung cancer concern mainly non-small cell cancers. Surgery, radiotherapy or drugs are offered alone or in combination depending on the patient and the extent of the disease. Involved in their implementation, the oncology nurse supports the patient throughout his or her treatment pathway.

Isolation of Nocardia beijingensis from a pulmonary abscess reveals human immunodeficiency virus infection.

A strain of Nocardia was isolated from a pulmonary abscess of a human immunodeficiency virus-infected patient in France. Comparative 16S rRNA gene sequence analysis revealed that the isolate represented a strain of Nocardia beijingensis. Antimicrobial susceptibility testing was essential to guide the clinicians to successfully treat this infection.

Prognostic value of health-related quality of life for overall survival in elderly non-small-cell lung cancer patients.

BACKGROUND: We investigated whether the health-related quality of life (HRQoL) score is a prognostic factor for overall survival (OS) in elderly patients with advanced non-small-cell lung cancer (NSCLC). METHODS: We included 451 NSCLC patients aged 70-89 years enrolled in the Intergroupe Francophone de Cancérologie Thoracique 0501 trial, using scores of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 at baseline to investigate the prognostic value of HRQoL for OS, in addition to conventional factors. Cox regression model was used for both univariate and multivariate analyses of OS. RESULTS: Global health status (GH) dimension score at baseline was associated with favourable OS when adjusted for clinical, functional, and histological factors (hazard ratio [HR]: 0.986; 95% confidence interval [CI]: 0.980-0.992). We distinguished three groups according to GH score: high (GH <46), intermediate (46 ≤ GH ≤ 67), and low (GH >67) mortality risk. The median OS values were 14.5, 8.2, and 5.3 months in the low-, intermediate-, and high-risk categories, respectively (log-rank P <0.0001). In the high-risk group, doublet chemotherapy was not associated with favourable OS (HR: 0.70; 95% CI: 0.49-1.003; P=0.052), whereas in the intermediate- and low-risk groups, doublet chemotherapy was associated with favourable OS (HR: 0.72; 95% CI: 0.54-0.96; P=0.023 and HR: 0.50; 95% CI: 0.30-0.84; P=0.0089, respectively). CONCLUSION: This study supports the additional prognostic value of HRQoL data at diagnosis to identify vulnerable subpopulations in elderly NSCLC patients. HRQoL could thus be valuable in selecting patients who will benefit from doublet chemotherapy.

Similar survival rates with first-line gefitinib, gemcitabine, or docetaxel in a randomized phase II trial in elderly patients with advanced non-small cell lung cancer and a poor performance status (IFCT-0301).

OBJECTIVES: We evaluated the impact of age in a randomized phase II trial that compared three first-line drugs in elderly patients with advanced non-small cell lung cancer (NSCLC) and a poor performance status (PS). MATERIALS AND METHODS: Patients with advanced NSCLC with a PS of 2 or 3 were enrolled into a multicenter randomized trial: arm A, gefitinib; arm B, gemcitabine; and arm C, docetaxel. We performed subgroup analyses according to age. RESULTS: Between December 2004 and June 2007, 127 patients were enrolled. Analyses were performed between the two subgroups aged <70years (younger, n=56) and ≥70years (older, n=71). Patients mainly had adenocarcinoma (46% young vs. 51%: elderly), of which 62% vs. 75% had a PS of 2, respectively. Significantly more elderly patients were women and non-smokers, and there was a non-significant trend towards more PS-2 among the elderly. Progression-free survival (PFS) was 1.4months (95% CI: 1.1-1.9) for younger compared to 2.3months (95% CI: 2.1-2.9) for elderly patients. Overall survival (OS) was 2.0months (95% CI: 1.5-2.4) and 3.7months (95% CI: 2.4-4.8), respectively. Toxicity did not differ between younger and older patients. NSCLC was better controlled in elderly patients after three cycles of monotherapy compared to younger patients (p=0.034). When adjusted for stratification criteria, age was the main prognostic factor for PFS. Adjusted HRs for PFS was 0.57 (95% CI: 0.38-0.85) for the elderly compared to patients aged <70years (p=0.004). CONCLUSIONS: Older patients had a decreased risk of progression/death compared to younger patients. Single-agent chemotherapy can be considered for patients aged ≥70years with a PS of 2.

[Standards, Options and Recommendations for the management of non-small cell lung carcinoma patients]. / Standards, Options et Recommandations 2000 pour la prise en charge des patients atteints d'un cancer bronchopulmonaire non á petites cellules (rapport abrégé).

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French cancer centers and specialists from French public university and general hospitals and private clinics. Its 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, according to the definitions of the Standards, Options and Recommendations, clinical practice guidelines for the management of non small cell lung carcinoma patients. METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups, then submitted for review to independent reviewers. This is a short version of the SOR guideline covering diagnosis, treatment and follow-up and includes the algorithms for the management of patients with non-small cell lung cancer.

[Results and lessons of an innovating chemotherapy-induced nauseas and vomiting management strategy]. / Résultats et enseignements d'une stratégie innovante de prise en charge des nausées et vomissements chimio-induits.

Current chemotherapy-induced nausea and vomiting management guidelines recommend taking into account the emetogenic potential of the chemotherapy employed as well as individual risk factors to such effects. We performed an interventional prospective study to assess the impact of an innovating therapeutic optimization strategy. The latter combines current guidelines application to a specific consultation in order to individualize the treatment. This study included 170 patients and covered a total of 1,746 days of various chemotherapies. Among these patients, 86.5% never vomited and 53.8% never had any nausea or vomiting. These results seem generally better than the ones found in the literature with all kinds of chemotherapies. Regarding them, we have attempted to highlight the determining criteria for a successful antiemetic treatment.

Efficacy of pemetrexed as second-line therapy in advanced NSCLC after either treatment-free interval or maintenance therapy with gemcitabine or erlotinib in IFCT-GFPC 05-02 phase III study.

INTRODUCTION: Maintenance therapy in advanced non-small-cell lung cancer (NSCLC) might lead to resistance to subsequent treatments. IFCT-GFPC 0502 study showed a progression-free survival (PFS) benefit with gemcitabine or erlotinib maintenance compared with observation after cisplatin-gemcitabine chemotherapy. The trial included a pre-defined pemetrexed second-line therapy, allowing post-hoc assessment of its efficacy according to previous maintenance treatment or treatment-free interval. METHODS: Stage IIIB/IV NSCLC patients were randomized after four cycles of cisplatin-gemcitabine chemotherapy to either observation or to receive maintenance therapy with gemcitabine or erlotinib. Pemetrexed was given as second-line treatment on disease progression in all arms. PFS and overall survival (OS) were assessed from the beginning of pemetrexed therapy according to randomization arm. RESULTS: Of the 464 randomized patients, 360 (78 %) received second-line pemetrexed (130 [84%], 114 [74%], and 116 [75%] in observation, gemcitabine, and erlotinib arm, respectively). Median number of pemetrexed cycles was 3 (1-40) in all arms. Median PFS did not differ between gemcitabine and observation arms (4.2 versus 3.9 months, hazard ratio [HR] [95% confidence interval [CI] 0.81 [0.62-1.06]) or between erlotinib and observation arms (4.2 versus 3.9 months, HR 0.83 [0.64-1.09]). OS data showed a non-significant improvement with gemcitabine arm versus observation arm (8.3 versus 7.5 months, HR 0.81 [0.61-1.07]) or erlotinib arm versus observation arm (9.1 versus 7.5 months, HR 0.80 [0.61-1.05]). Results were similar for non-squamous patients. Grade 3 to 4 treatment-related adverse events (AEs) were comparable in all arms. CONCLUSIONS: Maintenance therapy with gemcitabine continuation or erlotinib does not seem to impair efficacy of second-line pemetrexed comparatively to administration after a treatment-free interval.

A comparative and integrative approach identifies ATPase family, AAA domain containing 2 as a likely driver of cell proliferation in lung adenocarcinoma.

PURPOSE: To identify genetic changes that could drive cancer pathogenesis in never and ever smokers with lung adenocarcinoma. EXPERIMENTAL DESIGN: We analyzed the copy number and gene expression profiles of lung adenocarcinomas in 165 patients and related the alterations to smoking status. Having found differences in the tumor profiles, we integrated copy number and gene expression data from 80 paired samples. RESULTS: Amplifications at 8q24.12 overlapping MYC and ATAD2 were more frequent in ever smokers. Unsupervised analysis of gene expression revealed two groups: in the group with mainly never smokers, the tumors expressed genes common to normal lung; in the group with more ever smokers, the tumors expressed "proliferative" and "invasive" gene clusters. Integration of copy number and gene expression data identified one module enriched in mitotic genes and MYC targets. Its main associated modulator was ATAD2, a cofactor of MYC. A strong dose-response relationship between ATAD2 and proliferation-related gene expression was noted in both never and ever smokers, which was verified in two independent cohorts. Both ATAD2 and MYC expression correlated with 8q24.12 amplification and were higher in ever smokers. However, only ATAD2, and not MYC, overexpression explained the behavior of proliferation-related genes and predicted a worse prognosis independently of disease stage in a large validation cohort. CONCLUSIONS: The likely driving force behind MYC contribution to uncontrolled cell proliferation in lung adenocarcinoma is ATAD2. Deregulation of ATAD2 is mainly related to gene amplification and is more frequent in ever smokers.

Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer.

PURPOSE: This phase III study investigated whether continuation maintenance with gemcitabine or switch maintenance with erlotinib improves clinical outcome compared with observation in patients with advanced non-small-cell lung cancer (NSCLC) whose disease was controlled after cisplatin-gemcitabine induction chemotherapy. PATIENTS AND METHODS: Four hundred sixty-four patients with stage IIIB/IV NSCLC without tumor progression after four cycles of cisplatin-gemcitabine were randomly assigned to observation or to gemcitabine (1,250 mg/m(2) days 1 and 8 of a 3-week cycle) or daily erlotinib (150 mg/day) study arms. On disease progression, patients in all three arms received pemetrexed (500 mg/m(2) once every 21 days) as predefined second-line therapy. The primary end point was progression-free survival (PFS). RESULTS: PFS was significantly prolonged by gemcitabine (median, 3.8 v 1.9 months; hazard ratio [HR], 0.56; 95% CI, 0.44 to 0.72; log-rank P < .001) and erlotinib (median, 2.9 v 1.9 months; HR, 0.69; 95% CI, 0.54 to 0.88; log-rank P = .003) versus observation; this benefit was consistent across all clinical subgroups. Both maintenance strategies resulted in a nonsignificant improvement in overall survival (OS); patients who received second-line pemetrexed or with a performance status of 0 appeared to derive greater benefit. Exploratory analysis showed that magnitude of response to induction chemotherapy may affect the OS benefit as a result of gemcitabine maintenance. Maintenance gemcitabine and erlotinib were well tolerated with no unexpected adverse events. CONCLUSION: Gemcitabine continuation maintenance or erlotinib switch maintenance significantly reduces disease progression in patients with advanced NSCLC treated with cisplatin-gemcitabine as first-line chemotherapy. Response to induction chemotherapy may affect OS only for continuation maintenance.

Randomized phase II trial of gefitinib or gemcitabine or docetaxel chemotherapy in patients with advanced non-small-cell lung cancer and a performance status of 2 or 3 (IFCT-0301 study).

BACKGROUND: To compare 3 treatment strategies in chemotherapy naive patients with advanced NSCLC and a PS 2-3. PATIENTS AND METHODS: Patients were assigned to gefitinib 250mg daily (n=43) or to gemcitabine (1250mg/m(2) d 1, 8 q 21d) (n=42) or docetaxel (75mg/m(2) d 1 q 21d) (n=42). Treatments were taken until progression or toxicity. The primary endpoint was progression-free survival. Secondary end points were response and overall survival. RESULTS: Disease control rates were 20.9%, 33.4% and 38.1%, respectively. Median PFS was 1.9 months in the gefitinib arm, 2.0 months in the gemcitabine arm and 2.0 months in the docetaxel arm (HR gemcitabine versus gefitinib: 0.74, 95%CI: [0.48; 1.16], HR docetaxel versus gefitinib: 0.67, 95%CI: [0.43; 1.05]). Median survival times were 2.2, 2.4 and 3.5 months, respectively (HR gemcitabine versus gefitinib: 0.76, 95%CI: [0.48; 1.20], HR docetaxel versus gefitinib: 0.69, 95%CI: [0.44; 1.09]). There were more grade 3-4 adverse events in the docetaxel arm when compared with either the gefitinib arm or the gemcitabine arm. CONCLUSION: In unselected NSCLC patients with PS 2-3, gefitinib, gemcitabine and docetaxel achieved similar results. Docetaxel was associated with higher rates of adverse events.

Bronchoscopy with the Vision Sciences BF100 disposable-sheath device: French experience after 328 procedures.

BACKGROUND: In spite of adhesion to recommended disinfection procedures, the transmission of infections by bronchoscopes is a permanent problem. OBJECTIVE: The new device may prevent nosocomial infections because it consists of two parts: a specific bronchoscope Vision Sciences BF100 and a single-use protective sheath for each procedure. The aim of this paper is to report our practice and the difficulties encountered when using this system. METHODS: We report our experience from 1997 to 2002 after 328 elective and emergency endoscopic procedures with the BF100 device. In a retrospective study, we describe the population and the incidents during procedure. We discuss the impact of the use of BF100 on the cost of bronchoscopies. RESULTS: The major constraint is the care required in assembling the optical device and disposable sheath. The intrinsic qualities of the optics are confirmed; any sample may be taken although image quality and suction capacity are inferior to videoscopes. Maneuverability is inferior to videoscopes, but improves with a short experience. In addition, this device is expensive. CONCLUSIONS: The technical performances of the BF100 device are inferior to those of videoscopes but the concept of sterile single-use sheaths is able to prevent the nosocomial infections related to bronchoscopes. Because of the cost, examination with the BF100 should be reserved to patients with proved or suspected infection (multiresistant bacteria, tuberculosis, hepatitis C and B virus, HIV, prions) and immunosuppression (hematologic diseases).