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1.
Eur Respir J ; 43(1): 240-9, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24114964

ABSTRACT

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.


Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , ErbB Receptors/antagonists & inhibitors , Lung Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Quinazolines/therapeutic use , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/pathology , Cohort Studies , Disease Progression , Erlotinib Hydrochloride , Female , Humans , Lung Neoplasms/pathology , Male , Treatment Failure , Treatment Outcome
2.
J Thorac Oncol ; 7(9): 1423-31, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22767177

ABSTRACT

HYPOTHESIS: This study explored whether chemotherapy after first-line gefitinib was effective in patients with advanced lepidic predominant adenocarcinoma (LPA), formerly advanced bronchioloalveolar carcinoma, who were enrolled in the Intergroupe Francophone de Cancérologie Thoracique (IFCT)-0401 trial. METHODS: Overall, 88 patients presenting advanced LPA were enrolled in the IFCT-0401 trial, receiving gefitinib as first-line therapy. No predefined second-line treatment was mandatory in the case of progression or limiting toxicity under gefitinib. However, the carboplatin plus paclitaxel regimen was recommended for patients with a performance status (PS) 0 or 1 and gemcitabine monotherapy for those with a PS 2. For these patients, data concerning treatment efficacy was collected from the IFCT-0401 trial database. RESULTS: In total, 47 patients (53%) received second-line treatment after the failure of gefitinib, with 43 having PS 0 or 1. Regarding treatment, 43 were treated with chemotherapy, with 38 receiving a platinum-doublet regimen (taxane-based, n = 29; gemcitabine-based, n = 9) and five receiving monotherapy (gemcitabine, n = 3; pemetrexed, n = 2). The overall response rate (ORR) to chemotherapy was 21% (95% confidence interval [CI]: 10-36), disease control rate 56% (95% CI: 40-71), and median progression-free survival (PFS) 3.0 months (95% CI: 2.4-4.9). For patients receiving a platinum doublet (n = 38), ORR was 21% (95% CI: 10-37), with disease control rate being 55% (95% CI: 38-71), and median PFS 2.9 months (95% CI: 2.4-4.4). For patients receiving taxane-based regimen (n = 29) and gemcitabine-based regimen (n = 12), ORR was 28% and 0%, respectively, with a median PFS of 3.3 and 2.0 months, respectively, (p = 0.0243). The two patients receiving pemetrexed experienced a prolonged response. Multivariate Cox model analysis revealed that only the use of taxane-based chemotherapy or pemetrexed was related to PFS. CONCLUSION: Platinum-doublet chemotherapy showed some effectiveness in treating advanced LPA patients after first-line gefitinib. Our findings also suggest that taxane-based chemotherapy and pemetrexed should be investigated further in future clinical trials.


Subject(s)
Adenocarcinoma, Bronchiolo-Alveolar/drug therapy , Adenocarcinoma, Mucinous/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Salvage Therapy , Adenocarcinoma, Bronchiolo-Alveolar/mortality , Adenocarcinoma, Bronchiolo-Alveolar/secondary , Adenocarcinoma, Mucinous/mortality , Adenocarcinoma, Mucinous/secondary , Aged , Carboplatin/administration & dosage , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/secondary , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Female , Follow-Up Studies , Gefitinib , Glutamates/administration & dosage , Guanine/administration & dosage , Guanine/analogs & derivatives , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Neoplasm Staging , Paclitaxel/administration & dosage , Pemetrexed , Prognosis , Prospective Studies , Quinazolines/administration & dosage , Survival Rate , Gemcitabine
3.
Bull Cancer ; 99(4): E43-8, 2012 Apr 01.
Article in English | MEDLINE | ID: mdl-22450449

ABSTRACT

BACKGROUND: Cisplatin is a pivotal drug in combined chemotherapy for non-small cell and small-cell lung cancers (NSCLC or SCLC), but its renal toxicity limits its use. Current guidelines recommend 24 h hydration: thus hospitalization is required. The aim of this retrospective study was to confirm the safety of short hydration before giving an intermediate-to-high dose of cisplatin in an outpatient clinic. PATIENTS AND METHODS: Patients eligible had NSCLC or SCLC and were being treated with a chemotherapy regimen that included cisplatin ≥ 75 mg/m(2). They were given the same short hydration protocol for 1 day. Nephrotoxicity was defined as ≥ grade 1 according to NCIC common toxicity criteria. Predictive factors for nephrotoxicity were analyzed. RESULTS: Three hundred and fifty-seven consecutive patients (median age 58 years, range: 25-81) were reviewed. Twenty-one patients (6%) had ≥ grade 1 nephrotoxicity and all except one had grade 1 toxicity according to NCIC criteria for common toxicity (SC < 1,5 N). Predictive factors independently associated with nephrotoxicity included associated co-morbid conditions (hypertension, diabetes, heart disease) (OR = 4.97 CI 95% [1.8-13.7] P = 0.002), initial serum creatinine ≥ 100 µmol/L (OR = 8.3 CI 95% [2.55-27.4] P = 0.0005), and dose cycle of cisplatin ≥ 100 mg/m(2) (OR = 10.8 CI 95% [3.6-32.5] P < 0.0001). CONCLUSION: Rapid outpatient administration of a single dose of cisplatin at ≥ 75 mg/m(2) is feasible without a high risk of nephrotoxicity.


Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Cisplatin/administration & dosage , Fluid Therapy/methods , Kidney Diseases/chemically induced , Lung Neoplasms/drug therapy , Small Cell Lung Carcinoma/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin/adverse effects , Creatinine/metabolism , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Docetaxel , Etoposide/administration & dosage , Female , Humans , Kidney/drug effects , Male , Middle Aged , Retrospective Studies , Taxoids/administration & dosage , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , Vinorelbine , Gemcitabine
4.
Lancet ; 378(9796): 1079-88, 2011 Sep 17.
Article in English | MEDLINE | ID: mdl-21831418

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adenocarcinoma/drug therapy , Adenocarcinoma/mortality , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/administration & dosage , Carboplatin/adverse effects , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/mortality , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Drug Administration Schedule , Female , Humans , Lung Neoplasms/mortality , Male , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Survival Rate , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , Vinorelbine , Gemcitabine
5.
Lung Cancer ; 70(3): 301-7, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20400201

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/physiopathology , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Docetaxel , Female , Gefitinib , Humans , Karnofsky Performance Status , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lung Neoplasms/physiopathology , Male , Middle Aged , Neoplasm Staging , Quinazolines/administration & dosage , Quinazolines/adverse effects , Survival Analysis , Taxoids/administration & dosage , Taxoids/adverse effects , Gemcitabine
6.
Lung Cancer ; 68(2): 185-91, 2010 May.
Article in English | MEDLINE | ID: mdl-19581016

ABSTRACT

There is no optimal established therapy for treating advanced or recurrent adenocarcinoma with bronchioloalveolar carcinoma features (ADC-BAC), and it remains unclear whether chemotherapy achieves therapeutic results comparable to those seen in the more common non-small lung carcinoma subtypes. In order to improve the decisions made during the treatment of advanced ADC-BAC, we attempted to better characterize the mucinous and non-mucinous ADC-BAC subtypes. Fifty pathological samples were obtained from 62 patients included in a multicenter prospective phase II trial (IFCT0401) conducted to evaluate gefitinib as a first-line therapy for non-resectable ADC-BAC. These samples were centrally reviewed and re-classified as non-mucinous (n=25) or mucinous (n=25) subtypes. We demonstrated that demographic data, clinical characteristics and stage at presentation (extrathoracic versus lung metastasis, as well as TNM staging) did not distinguish between the two subtypes. In contrast, three biological markers (PAS staining, TTF-1 expression and EGFR genomic gain combined with mutation analysis) enabled us to independently segregate all but 2 of the 50 patients into the mucinous and non-mucinous ADC-BAC subtypes. Finally, only mucinous tumors appeared to be resistant to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Additional prospective studies are required to better approach therapeutic strategy in mucinous tumors, which are a distinct entity from non-mucinous tumors.


Subject(s)
Adenocarcinoma, Bronchiolo-Alveolar/diagnosis , Adenocarcinoma, Mucinous/diagnosis , DNA-Binding Proteins/metabolism , ErbB Receptors/genetics , Lung Neoplasms/diagnosis , Adenocarcinoma, Bronchiolo-Alveolar/drug therapy , Adenocarcinoma, Bronchiolo-Alveolar/pathology , Adenocarcinoma, Bronchiolo-Alveolar/physiopathology , Adenocarcinoma, Mucinous/drug therapy , Adenocarcinoma, Mucinous/pathology , Adenocarcinoma, Mucinous/physiopathology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/analysis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , DNA Mutational Analysis , DNA-Binding Proteins/genetics , Disease Progression , Drug Resistance, Neoplasm , ErbB Receptors/antagonists & inhibitors , Female , Gefitinib , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/physiopathology , Male , Middle Aged , Quinazolines/therapeutic use , Transcription Factors
7.
J Thorac Oncol ; 4(9): 1126-35, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19574932

ABSTRACT

PURPOSE: Intergroupe Francophone de Cancérologie Thoracique-0401 phase II trial aimed to evaluate the efficacy and safety of gefitinib as a first-line treatment for patients with adenocarcinoma with bronchioloalveolar carcinoma subtype (ADC-BAC). METHODS: Chemotherapy-naive patients (n = 88) with advanced ADC-BAC were treated with 250 mg/d of gefitinib. The primary objective was assessment of disease control rate (DCR [objective response + stable disease]) at 3 months using World Health Organization criteria. A disease control rate of 25% or greater would be of interest in this patient population. Progression-free survival (PFS), overall survival (OS), and toxicity were the secondary criteria. Clinical and disease characteristics that conferred a favorable prognosis under gefitinib were also analyzed. RESULTS: Disease control was achieved in 25 patients (29.4%); 11 patients (12.9%) had partial response and 14 (16.4%) had stable disease. Median PFS was 2.9 months (95% confidence interval [CI], 2.3-3.2) and median OS was 13.2 months (95% CI, 10.2-17.3). Never smokers, patients with low respiratory symptoms score, occurrence of cutaneous rash, and nonmucinous ADC-BAC subtype were associated with increased probability of disease control. Nonmucinous ADC-BAC was associated with increased PFS and OS at 3 years. Patients with nonmucinous BAC had longer OS and PFS compared with patients with other ADC-BAC variants; median PFS for nonmucinous BAC was 11.3 months (95% CI, 3.2-14.7), whereas it was 2.6 months (95% CI, 2.1-3) for mucinous BAC. As expected, toxicity was low, with dermatological problems, diarrhea, and nausea being the most common adverse events. CONCLUSION: Results from the Intergroupe Francophone de Cancérologie Thoracique-0401 trial demonstrate that gefitinib combines efficacy with low toxicity and is, therefore, suitable as a first-line treatment of advanced ADC-BAC, particularly in patients with nonmucinous BAC subtype.


Subject(s)
Adenocarcinoma, Bronchiolo-Alveolar/drug therapy , Adenocarcinoma/drug therapy , Antineoplastic Agents/therapeutic use , ErbB Receptors/antagonists & inhibitors , Lung Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Quinazolines/therapeutic use , Adenocarcinoma/mortality , Adenocarcinoma, Bronchiolo-Alveolar/mortality , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Gefitinib , Humans , Lung Neoplasms/mortality , Male , Middle Aged , Quinazolines/adverse effects
8.
Lung Cancer ; 65(3): 345-50, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19135758

ABSTRACT

OBJECTIVE: To evaluate the impact of highly active antiretroviral therapy (HAART) on survival in HIV infected patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: All consecutive HIV infected patients with NSCLC diagnosed between 06/1996 and 03/2007 at two University hospitals in Paris (France) were prospectively followed until death. The association between survival and clinical and biological factors was analyzed by univariate and multivariate models. Survival analysis was performed by Kaplan-Meier estimates and the Cox proportional hazards regression model. RESULTS: During the study period, NSCLC was diagnosed in 49 consecutive HIV infected patients (median age 46 years); 84% had advanced disease. Median survival was 8.1 months (range 5-10 months). In multivariate analysis, baseline parameters with significant positive impact on survival included performance status (PS) < or =1 (HR=0.2, 95%CI [0.09, 0.46], p=0.0001), stage I-II disease (HR=0.15, 95%CI [0.04, 0.53], p=0.003), and use of HAART (HR=0.4, 95%CI [0.2, 0.9], p=0.027). CONCLUSION: HAART is a good prognostic factor for survival in HIV infected patients with NSCLC. Stage of disease and PS are two other valid survival prognostic factors.


Subject(s)
Antiretroviral Therapy, Highly Active , Carcinoma, Non-Small-Cell Lung/drug therapy , HIV Infections/drug therapy , HIV-1/physiology , Lung Neoplasms/drug therapy , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Disease Progression , Female , HIV Infections/complications , HIV Infections/diagnosis , HIV Infections/mortality , Humans , Lung Neoplasms/complications , Lung Neoplasms/diagnosis , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Prognosis , Survival Analysis , Virus Replication/drug effects
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