Pooled Analysis of Elderly Patients with Non-small Cell Lung Cancer Treated with Front Line Docetaxel/Gemcitabine Regimen: The Hellenic Oncology Research Group Experience

IntroductionThirty to 40% of patients with non-small cell lung cancer (NSCLC) are older than 70 years and rarely are enrolled in clinical trials. Moreover, in clinical practice, >75% of patients older than 65 years with metastatic NSCLC never receive any kind of chemotherapy.PurposeTo retrospectively evaluate the impact of age on efficacy and toxicity of chemotherapy regimens in patients with advanced NSCLC treated with the docetaxel-gemcitabine combination.Patients and MethodsPooled data from six clinical trials of the Hellenic Oncology Research Group were analyzed. According to their age, patients were divided into two groups: those with age <70 years and those with ≥70 years.ResultsA total of 858 patients were included in this analysis. Six hundred sixty-six (77.6%) patients were younger than 70 years, whereas 192 (22.4%) patients where ≥70-year-old. Overall response rate was 30.3% and 30.2% for patients <70 years and ≥70 years, respectively (p = 0.974). The median time to tumor progression was 4.1 and 4.5 months for patients <70 years and ≥70 years, respectively (p = 0.948). Median overall survival was 9.9 and 9.2 months for patients <70 and ≥70, respectively (p = 0.117). The multivariate analysis revealed performance status (PS) (p = 0.0001) and stage (p = 0.0001) as independent factors with significant impact on the hazard of death. Chemotherapy was well tolerated, but the incidence of grade III/IV mucositis was significantly higher in elderly patients (0.2% versus 1.5% for patients <70 versus ≥70 years, respectively; p = 0.011).ConclusionThe docetaxel/gemcitabine regimen has a comparable efficacy and tolerance in young (<70 years) and elderly (≥70 years) patients

A randomized phase III study of the docetaxel/carboplatin combination versus docetaxel single-agent as second line treatment for patients with advanced/metastatic Non-Small Cell Lung Cancer

<p>Abstract</p> <p>Background</p> <p>To compare the activity and toxicity of docetaxel/carboplatin (DC) doublet vs single agent docetaxel (D) as second-line treatment in patients with advanced non-small cell lung cancer (NSCLC).</p> <p>Methods</p> <p>Patients pre-treated with front-line platinum-free regimens, were randomized to receive either docetaxel/carboplatin (DC), (docetaxel 50 mg/m²; carboplatin AUC4; both drugs administered on days 1 and 15) or docetaxel single-agent (D), (docetaxel 50 mg/m²on days 1 and 15).</p> <p>Results</p> <p>Response rate was similar between the two arms (DC vs D: 10.4% vs 7.7%; p = 0.764). After a median follow-up time of 28.0 months for DC arm and 34.5 months for D arm, progression free survival (PFS) was significantly higher in the DC arm (DC vs D:3.33 months vs 2.60 months; p-value = 0.012), while no significant difference was observed in terms of overall survival (OS) (DC vs D: 10.3 months vs 7.70 months; p-value = 0.550). Chemotherapy was well-tolerated and grade III/IV toxicities were relatively infrequent. No toxic deaths were observed.</p> <p>Conclusions</p> <p>This study has not achieved its primary objective of significant OS prolongation with docetaxel/carboplatin combination over single-agent docetaxel in patients who had not received front-line docetaxel; however, the docetaxel/carboplatin combination was associated with a significant clinical benefit in terms of PFS.</p

Systematic review of the relationship between family history and lung cancer risk

We performed a systematic review of 28 case–control, 17 cohort and seven twin studies of the relationship between family history and risk of lung cancer and a meta-analysis of risk estimates. Data from both case–control and cohort studies show a significantly increased lung cancer risk associated with having an affected relative. Risk appears to be greater in relatives of cases diagnosed at a young age and in those with multiple affected family members. Increased lung cancer risk was observed in association with an affected spouse and twin studies, while limited, favour shared environmental exposures. The limitations of the currently published epidemiological studies to infer genetic susceptibility are discussed

Protection of Historical Mortars through Treatment with Suspensions of Nanoparticles

Mortars, which are very important elements for the integrity of historic monuments, consist mainly of calcium carbonate and silicates in different proportions. Chemical dissolution due to exposure in open air is very important for the degradation of mortars. Inorganic nanoparticles with chemical and crystallographic affinity with mortar components are expected to be effective structure stabilizers and agents offering resistance to chemical dissolution. In the present work, we have developed and applied suspensions of amorphous calcium carbonate (ACC), silicon oxide (am-SiO2) and composite nanoparticles by the precipitation of ACC on am-SiO2 and vice versa. The application of suspensions of the synthesized nanoparticles on three different historical mortars of Roman times (1st century AD), retarded their dissolution rate in solutions undersaturated with respect to calcite, in acid pH (6.50, 25 °C). All three test historic mortars, treated with suspensions of the nanoparticles prepared, showed high resistance towards dissolution at pH 6.50. The ability of the nanoparticles’ suspension to consolidate the damaged mortar was the key factor in deciding the corresponding effectiveness in the retardation of the rate of dissolution. The combination of ACC with am-SiO2 nanoparticles showed high efficiency for protection from the dissolution of calcite rich mortars

Protection of Historical Mortars through Treatment with Suspensions of Nanoparticles

Mortars, which are very important elements for the integrity of historic monuments, consist mainly of calcium carbonate and silicates in different proportions. Chemical dissolution due to exposure in open air is very important for the degradation of mortars. Inorganic nanoparticles with chemical and crystallographic affinity with mortar components are expected to be effective structure stabilizers and agents offering resistance to chemical dissolution. In the present work, we have developed and applied suspensions of amorphous calcium carbonate (ACC), silicon oxide (am-SiO2) and composite nanoparticles by the precipitation of ACC on am-SiO2 and vice versa. The application of suspensions of the synthesized nanoparticles on three different historical mortars of Roman times (1st century AD), retarded their dissolution rate in solutions undersaturated with respect to calcite, in acid pH (6.50, 25 &deg;C). All three test historic mortars, treated with suspensions of the nanoparticles prepared, showed high resistance towards dissolution at pH 6.50. The ability of the nanoparticles&rsquo; suspension to consolidate the damaged mortar was the key factor in deciding the corresponding effectiveness in the retardation of the rate of dissolution. The combination of ACC with am-SiO2 nanoparticles showed high efficiency for protection from the dissolution of calcite rich mortars

The Protection of Building Materials of Historical Monuments with Nanoparticle Suspensions

Marble and limestone have been extensively used as building materials in historical monuments. Environmental, physical, chemical and biological factors contribute to stone deterioration. The rehabilitation of stone damage and the delay of further deterioration is of utmost importance. Inorganic nanoparticles having chemical and crystallographic affinity with building materials is very important for the formation of protective coatings or overlayers. In the present work, we have tested the possibility of treating calcitic materials with suspensions of amorphous calcium carbonate (am-CaCO3, ACC) and amorphous silica (AmSiO2). Pentelic marble (PM) was selected as the test material to validate the efficiency of the nanoparticle suspension treatment towards dissolution in undersaturated solutions and slightly acidic pH (6.50). Suspensions of ACC and AnSiO2 nanoparticles were prepared by spontaneous precipitation from supersaturated solutions and by tetraethyl orthosilicate (TEOS) hydrolysis, respectively. The suspensions were quite stable (nine days for ACC and months for AmSiO2). ACC and Am SiO2 particles were deposited on the surface of powdered PM. The rates of dissolution of PM were measured in solutions undersaturated with respect to calcite at a constant pH of 6.50. For specimens treated with ACC and AmSiO2 suspensions, the measured dissolution rates were significantly lower. The extent of the rate of dissolution reduction was higher for AmSiO2 particles on PM. Moreover, application of the nanoparticles on the substrate during their precipitation was most efficient method

A multicenter phase II study of the combination of irinotecan and gemcitabine in previously treated patients with small-cell lung cancer

Objective: To evaluate efficacy and toxicity of the combination of irinotecan and gemcitabine in pretreated patients having small-cell lung cancer. Patients and Methods: Thirty-one patients ( median age 60 years, performance status 0-1 in 87% and 2 in 13% of the patients) with limited or extensive-stage disease, refractory or relapsing after at least one prior chemotherapy regimen, received gemcitabine 1,000 mg/m(2) on days 1 and 8 and irinotecan 300 mg/m(2) on day 8, every 21 days. Sixteen (52%) patients had sensitive and 15 (48%) refractory disease. Fifteen patients (48%) had received 62 prior regimens. Results: All patients were evaluable for toxicity and 26 for response analysis. A median of three ( range 1-6) cycles per patient was administered. Three partial responses were documented for an overall response rate of 10% (95% CI 0.73-20.09), and disease stabilization was obtained in 7 patients (22%; intention-to-treat analysis). Two of the responders had refractory, and 1 had sensitive disease. The median time to progression was 4.5 months, the median duration of responses was 2.5 months, and the median survival time was 6 months. Grade 3-4 ( WHO) neutropenia was observed in 9 patients (29%), grade 3-4 thrombocytopenia in 4 (13%), and grade 3-4 diahrrea in 3 patients (10%). Three patients experienced febrile neutropenia. No toxic deaths occurred. Conclusions: The combination showed modest activity in this patient group with a poor prognosis. Thus we believe it merits further investigation in the treatment of patients with small-cell lung cancer who have failed one prior chemotherapy regimen. Copyright (C) 2004 S. Karger AG, Basel

Sequential versus alternating administration of cisplatin/etoposide and topotecan as first-line treatment in extensive-stage small-cell lung cancer: Preliminary results of a phase III trial of the hellenic oncology research group

Background: This trial was designed to compare the efficacy and toxicity of sequential versus alternating administration of cisplatin/etoposide and topotecan in patients with previously untreated extensive-stage small-cell lung cancer (SCLC). Patients and methods: Two hundred eighty-four chemotherapy-naive patients were randomized between the sequential therapy arm (n = 142; 4 cycles of cisplatin 75 mg/m2 intravenously [I.V.] on day 1 with etoposide 100 mg/m2 per day I.V. on days 1-3 followed by 4 cycles of topotecan 1.5 mg/m2 per day I.V. on days 1-5) and the alternating arm (n = 142; same doses of cisplatin/etoposide on cycles 1, 3, 5, and 7 and topotecan on cycles 2, 4, 6, and 8). Treatment cycles for both regimens were administered every 3 weeks. Results: At this preliminary analysis, no statistically significant difference in the overall response rate, duration of response, time to disease progression, or median survival was observed between the 2 arms. A total of 756 cycles of the sequential therapy and 830 cycles of the alternating therapy were administered, with a median numbers of 6 and 7 cycles per patient, respectively. Topotecan was administered in 85 patients on the sequential arm and 132 patients on the alternating arm. Dose reductions for toxicity were similar in both arms. Grade 3/4 toxicities in the sequential and alternating arms, respectively, included neutropenia (51% and 52%; P = NS), anemia (12% and 11%; P = NS), febrile neutropenia (7% and 9%; P = NS), thrombocytopenia (19% and 20%; P = NS), and asthenia (8% and 2%; P = 0.02). There were 4 toxicity-related deaths in the sequential arm versus 3 in the alternating arm. Conclusion: Our preliminary conclusion is that the sequential and alternating regimens resulted in comparable activity and tolerability in previously untreated patients with extensive-stage SCLC