Prevalence of EGFR mutations in newly diagnosed locally advanced or metastatic non-small cell lung cancer Spanish patients and its association with histological subtypes and clinical features: The Spanish REASON study.

BACKGROUND AND OBJECTIVES: The aim of the REASON study is to determine the frequency of EGFR mutation in advanced non-small cell lung cancer (aNSCLC) patients in Spain (all histologies), and to better understand the clinical factors (gender, smoking habits and histological subtypes) that may be associated with EGFR mutations, in an unselected sample of aNSCLC patients. METHODS: All newly diagnosed aNSCLC patients from 40 selected centers in Spain were prospectively included for a 6-month period. Patient characteristics were obtained from clinical records. Mutation testing was performed on available tumor samples. Exploratory analyses were performed to characterize the clinico-pathological factors associated with presence of EGFR mutations. RESULTS: From March 2010 to March 2011, 1113 patients were included in the study, of which 1009 patients provided sample for EGFR mutation analysis (90.7%). Mutation analysis was not feasible in 146/1113 patients (13.1%) due to either sample unavailability (79/1113; 7.1%) or sample inadequacy (67/1113; 6.0%). Twenty-five out of 1113 patients (2.3%) were excluded due to unavailable information. Most patients (99.5%) were Caucasian, 74.5% were male, and predominantly were current (38.1%) or former smokers (44.0%). Median age was 66 years (range 25-90) and 70.7% of patients had non-squamous histology (57.8% adenocarcinoma, 1.8% bronchoalveolar, 11.1% large-cell carcinoma). Exon 19 deletions and the exon 21 L858R point mutation were analyzed in 942/1009 (93.4%) samples. Mutation rate was 11.6% (82.6% exon 19 dels and 17.4% L858R). To be never smoker (38.1%), female (25.4%), with bronchioloalveolar carcinoma (22.2%) or adenocarcinoma (15.4%) histology was associated with a higher prevalence of EGFR mutations. Exons 18, 20 and 21 (excluding L858R) were analyzed in 505/942 samples, and EGFR mutations were found in 22/505 samples (4.4%). CONCLUSION: The estimated prevalence of sensitizing EGFR mutations (exon 19 del, exon 21 L858R) in an unselected samples of newly diagnosed aNSCLC patients in Spain (all histologies) is consistent with previous published data in Caucasian patients. When a sample is available, EGFR mutation testing is feasible in over 90% of cases, and may therefore be suitable for routine clinical practice. CLINICALTRIALS. GOV IDENTIFIER: NCT01081496.

Phase II clinical trial with gemcitabine and paclitaxel sequential monotherapy as first-line treatment for advanced non-small-cell lung cancer (SLCG 01-04)

BACKGROUND: In advanced-stage (IIIB or IV) non-small-cell lung cancer (NSCLC), combination chemotherapy has demonstrated response rates of 20% and a 1-year survival rate of 30%. We conducted a multicentre, open-label, nonrandomised phase II trial to determine the efficacy and tolerability of sequential monotherapy with gemcitabine followed by paclitaxel in chemotherapy-naïve patients with advanced NSCLC. MATERIALS AND METHODS: Between December 2002 and July 2004, the Spanish Lung Cancer Group (SLCG) conducted a study in which 34 patients with advanced (stage IIIB or IV) NSCLC received 1200 mg/m(2) of i.v. gemcitabine on days 1, 8 and 15 of each 28-day cycle for a total of 3 cycles followed by 100 mg/m(2) of weekly i.v. paclitaxel for a maximum of 8 weeks. If objective response or stable disease was achieved, 70 mg/m(2) of weekly i.v. paclitaxel was maintained until disease progression was evident or toxic effects were intolerable. Lung Cancer Symptom Scale (LCSS) analysis was performed. Baseline levels of serum VEGF, EGFR, telomerase reverse transcriptase (hTERT) and K-ras mutations were analysed. The primary endpoint was the objective response rate. RESULTS: The median age of the 34 patients who were enrolled was 67 years (range 46-77), but later 8 patients were excluded; 78.8% were men, 81.8% had performance status 1 and also 81.8% had metastatic disease at diagnosis. The objective response rate was 28% (95% CI, 14.2-47.8); the median overall survival was 7.2 months (95% CI, 2.1-12.3) and the median time to progression (TTP) was 3.1 months (95% CI, 2.5-5.3). Grade 3 or 4 drug-related haematological toxicities were observed in 6 patients. Patients with lower baseline serum VEGF levels had significantly longer survival. CONCLUSIONS: Sequential therapy with gemcitabine followed by paclitaxel was well tolerated with a low proportion of grade 3 or 4 adverse events, the absence of unexpected toxicity and with an improvement in quality of life. Unfortunately, the response rate did not meet the minimally required rate of 20% and the study was prematurely closed. VEGF was identified as a poor prognostic factor for TTP and survival (AU)

Assessment of functional status, symptoms and comorbidity in elderly patients with advanced non-small-cell lung cancer (NSCLC) treated with gemcitabine and vinorelbine.

BACKGROUND: The incidence and prevalence of comorbid conditions in lung cancer patients increase with age. The aim of the study was to determine response and tolerability with the biweekly combination gemcitabine-vinorelbine in elderly non-small-cell lung cancer (NSCLC) patients. In order to characterise the population included in the study well and assess the results achieved properly, an evaluation of the functional status, comorbidity and survival was performed. PATIENTS AND METHOD: Between June 2001, and December 2003, 59 untreated advanced NSCLC patients over the age of 70 years entered the study. Treatment consisted of gemcitabine 1750 mg/m(2) and vinorelbine 30 mg/m(2) on day 1 every two weeks. The response was evaluated every f ive cycles (RECIST guidelines). Comorbidity was evaluated according to the Charlson and Kaplan Feinstein scales. To measure functional status, activities of daily living (ADL) and instrumental ADL (IADL) were considered. RESULTS: Median age was 74; ECOG performance status was >2 in 59.3%; no dependence in ADL or IADL was found in 24.8% and 42.4% of patients, respectively. A total of 381 courses were administered. Grade 3-4 neutropenia was present in 6.8% of these courses and correlated with IADL. Objective response was 22% (95% CI 12-32). Mean global survival and cause-specific survival were 29 weeks (95% CI 19.9-38.1) and 32 weeks (95% CI 23.4-40.8) respectively. Comorbidity displayed no close correlation with functional status, but comorbidity according to the Kaplan Feinstein index correlated with IADL. Performance status, ADL, IADL and weight loss were significantly related to survival in multivariate analysis. CONCLUSIONS: This biweekly combination is feasible in elderly lung cancer patients with a high burden of comorbidity and dependence. Toxicity is acceptable, whereas response rate and survival fall in the range of active regimens. ADL and IADL indices allow the identification of elderly patients with a worse prognosis.

Assessment of functional status, symptoms and comorbidity in elderly patients with advanced non-small-cell lung cancer (NSCLC) treated with gemcitabine and vinorelbine

BACKGROUND: The incidence and prevalence of comorbid conditions in lung cancer patients increase with age. The aim of the study was to determine response and tolerability with the biweekly combination gemcitabine-vinorelbine in elderly non-small-cell lung cancer (NSCLC) patients. In order to characterise the population included in the study well and assess the results achieved properly, an evaluation of the functional status, comorbidity and survival was performed. PATIENTS AND METHOD: Between June 2001, and December 2003, 59 untreated advanced NSCLC patients over the age of 70 years entered the study. Treatment consisted of gemcitabine 1750 mg/m(2) and vinorelbine 30 mg/m(2) on day 1 every two weeks. The response was evaluated every f ive cycles (RECIST guidelines). Comorbidity was evaluated according to the Charlson and Kaplan Feinstein scales. To measure functional status, activities of daily living (ADL) and instrumental ADL (IADL) were considered. RESULTS: Median age was 74; ECOG performance status was >2 in 59.3%; no dependence in ADL or IADL was found in 24.8% and 42.4% of patients, respectively. A total of 381 courses were administered. Grade 3-4 neutropenia was present in 6.8% of these courses and correlated with IADL. Objective response was 22% (95% CI 12-32). Mean global survival and cause-specific survival were 29 weeks (95% CI 19.9-38.1) and 32 weeks (95% CI 23.4-40.8) respectively. Comorbidity displayed no close correlation with functional status, but comorbidity according to the Kaplan Feinstein index correlated with IADL. Performance status, ADL, IADL and weight loss were significantly related to survival in multivariate analysis. CONCLUSIONS: This biweekly combination is feasible in elderly lung cancer patients with a high burden of comorbidity and dependence. Toxicity is acceptable, whereas response rate and survival fall in the range of active regimens. ADL and IADL indices allow the identification of elderly patients with a worse prognosis (AU)

Gemcitabine and low dose carboplatin in the treatment of elderly patients with advanced non-small cell lung cancer.

BACKGROUND: Fifty percent of lung cancers arise in patients over 65 years old and 30% in those over 70. The aim of this study was to evaluate response, survival and tolerability of the combination carboplatin-gemcitabine in elderly patients with advanced non-small cell lung cancer (NSCLC). METHODS: Between May 1998 and December 2000, 88 patients were included. Median age was 74 (range 65-83). Treatment consisted of gemcitabine 1250 mg/m(2) (1000 mg/m(2) in the first six patients) on days 1 and 8, and carboplatin AUC=4 on day 1, every 21 days. Prognostic factors for survival were analysed. Performance status (PS) and symptoms were evaluated before and after three and six courses. RESULTS: A total of 400 cycles were administered (median of four per patient). WHO grades 3-4 toxicities were: neutropenia in 13% of the cycles, thrombocytopenia and anaemia in 4.5 and 14.7% of patients in any cycle. There was one treatment-related death. According to the intent-to-treat analysis, 33 patients achieved objective response, 33 had stable disease, and 22 had treatment failure (progression in 18 patients). Median and 1 year survival were 9 months and 34%, respectively. Median time to progression was 8 months. Only disease stage and PS showed independent prognostic value. Comorbidity and PS displayed no close correlation. Symptom improvement was seen as follows: pain (61.7%), dyspnea (50%), haemoptysis (80%), anorexia (62.5%) and asthenia (61.5%). CONCLUSIONS: The combination carboplatin-gemcitabine at these doses is feasible in elderly patients with advanced non-small cell lung cancer. Tolerability and toxicity are acceptable. Response rate and survival stand in the range of the most active regimens. Comorbidity and PS showed prognostic independence.

Extragonadal nongestational choriocarcinoma involving the lung: a report of three cases.

Primary choriocarcinoma of the lung is an extremely rare tumour, with about 20 cases reported in the literature. The case records of 3 female patients with nongestational, extragonadal choriocarcinoma apparently arising in the lung are presented to illustrate its clinical spectrum, the utility of serum beta human chorionic gonadotropin, and responsiveness to chemotherapy. Most plausible origins of these malignancies and differential diagnosis are briefly discussed.