Phase II study of continuous daily sunitinib dosing in patients with previously treated advanced non-small cell lung cancer.

BACKGROUND: Sunitinib malate (SUTENT) has promising single-agent activity given on Schedule 4/2 (4 weeks on treatment followed by 2 weeks off treatment) in advanced non-small cell lung cancer (NSCLC). METHODS: We examined the activity of sunitinib on a continuous daily dosing (CDD) schedule in an open-label, multicentre phase II study in patients with previously treated, advanced NSCLC. Patients > or =18 years with stage IIIB/IV NSCLC after failure with platinum-based chemotherapy, received sunitinib 37.5 mg per day. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), overall survival (OS), 1-year survival rate, and safety. RESULTS: Of 47 patients receiving sunitinib, one patient achieved a confirmed partial response (ORR 2.1% (95% confidence interval (CI) 0.1, 11.3)) and 11 (23.4%) had stable disease (SD) > or =8 weeks. Five patients had SD>6 months. Median PFS was 11.9 weeks (95% CI 8.6, 14.1) and median OS was 37.1 weeks (95% CI 31.1, 69.7). The 1-year survival probability was 38.4% (95% CI 24.2, 52.5). Treatment was generally well tolerated. CONCLUSIONS: The safety profile and time-to-event analyses, albeit relatively low response rate of 2%, suggest single-agent sunitinib on a CDD schedule may be a potential therapeutic agent for patients with advanced, refractory NSCLC.

Induction chemotherapy with paclitaxel plus carboplatin followed by paclitaxel with concurrent radiotherapy in stage IIIB non-small-cell lung cancer (NSCLC) patients: a phase II trial.

PURPOSE: We conducted a prospective phase II trial to evaluate the efficacy and toxicity of induction chemotherapy with paclitaxel plus carboplatin followed by concurrent radiotherapy with weekly paclitaxel in stage IIIB non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Patients with stage IIIB NSCLC received two 3-week cycles of paclitaxel 200mg/m(2) combined with carboplatin (target area under the plasma concentration curve (AUC) of 6 mg/ml) followed by weekly paclitaxel 50mg/m(2) concurrently with radiotherapy consisted of 2 Gy daily, 5 days per week (60 Gy total dose in 6 weeks). The median follow-up period was 5 years. RESULTS: Between March 1999 and January 2002, 21 patients were enrolled and analyzed. Ninety percent of patients completed the planned treatment schedule. The overall response rate was 76% (24% complete response and 52% partial response). The median overall survival time was 15 months and the 1-year, 2-year and 5-year overall survival rates were 57, 33 and 24%, respectively. The disease progression rate at 1 year was 43% and the median progression-free survival was 8 months. During the chemoradiation period, grade 3-4 oesophagitis and pneumonitis were observed in 24 and 14% of patients, respectively. CONCLUSIONS: Induction chemotherapy with carboplatin and paclitaxel followed by weekly paclitaxel with concurrent radiotherapy was found to be active and tolerable in selected stage IIIB NSCLC patients. Further studies are needed to improve the safety profile and outcome in this setting.

[Clinical utility of attenuation correction with X-rays in myocardial perfusion SPECT studies]. / Utilidad clínica de la corrección de atenuación con rayos X en los estudios SPECT de perfusión miocárdica.

OBJECTIVE: We have compared the uncorrected images of SPECT myocardial perfusion plus gated data with corrected images with X-rays in the management of coronary artery disease. METHODS: In 60 patients (p) a stress/rest-gated myocardial perfusion SPECT was performed with attenuation correction with a hybrid gammacamera. All patients underwent cardiac catheterization. 3 types of images were qualitatively evaluated: uncorrected stress/rest (NC), uncorrected stress/rest plus gated (NCG) and stress/rest corrected for attenuation with scatter correction (AC). McNemar's test was used to analyze the statistical differences in assessing the diagnostic accuracy of each type of images; p < 0.05 was considered statistically significant. RESULTS: Fourteen p did not have significant lesions in the coronary arteries (NSL), 46 p showed lesions in coronary arteries: 29 in anterior descending, 26 in right coronary and 18 in circumflex. In right coronary territory, diagnostic accuracy was significantly higher on AC than on NC images (p < 0.001) and on AC than on NCG images (p < 0.01). In NSL group there are significant differences between NC and AC (p < 0.02) and between NCG and AC (p < 0.05). CONCLUSIONS: Attenuation correction with X-rays significantly improves diagnostic accuracy of uncorrected images and uncorrected images plus gated.

Vegetable and fruit intake and the risk of lung cancer in women in Barcelona, Spain.

A case-control study on women was carried out in Barcelona, Spain, to investigate the relationship of lung cancer with the intake of vegetables, fruits and some foods of animal origin. The study included 103 cases and 206 controls matched by age and residence. Diet intake was assessed by means of a food frequency questionnaire. A reduction in risk, adjusted for smoking habit, was found for the intake of yellow/orange vegetables (mainly carrots) and tomatoes. The odds ratio (OR) and 95% confidence interval (CI) for the highest versus lowest tertile of intake were 0.37 (0.19-0.74) for yellow/orange vegetables and 0.45 (0.22-0.91) for tomatoes; both had a significant inverse trend. A tendency to a reduction in risk of lung cancer with increased intake was observed for all vegetables, leafy green vegetables, dark green vegetables and cruciferous, but these associations did not reach statistical significance. No association with lung cancer was found for the intake of fruits or foods of animal origin rich in retinol. Similar patterns were observed for women who never smoked and when the analysis was restricted to adenocarcinoma.

Synthesis of aryl 3-O-beta-cellobiosyl-beta-D-glucopyranosides for reactivity studies of 1,3-1,4-beta-glucanases.

A series of substituted aryl beta-glycosides derived from 3-O-beta-cellobiosyl-D-glucopyranose with different phenol-leaving group abilities as measured by the pKa of the free phenol group upon enzymatic hydrolysis has been synthesised. Aryl beta-glycosides with a pKa of the free phenol leaving group > 5 were prepared by phase-transfer glycosidation of the per-O-acetylated alpha-glycosyl bromide with the corresponding phenol, whereas the 2,4-dinitrophenyl beta-glycoside was obtained by condensation of 1-fluoro-2,4-dinitrobenzene with the partially acetylated trisaccharide followed by acid de-O-acetylation. The aryl beta-glycosides have been used for reactivity studies of the wild-type Bacillus licheniformis 1,3-1,4-beta-D-glucan 4-glucanohydrolase. The Hammett plot log kcat versus pKa is biphasic with an upward curvature at low pKa values suggesting a change in transition-state structure depending on the aglycon.

[Impact of thrombolytic therapy on short and long-term survival of a cohort of patients with acute myocardial infarction consecutively admitted to all the hospitals of a health care area. GESIR-5 study]. / Impacto de la trombólisis sobre la supervivencia a corto y largo plazo de una cohorte de pacientes con infarto agudo de miocardio atendidos de forma consecutiva en todos los hospitales de una región sanitaria. Estudio GESIR-5.

AIM: This study aims to assess the application of thrombolysis in patients with acute myocardial infarction admitted to all the hospitals of a health care area in Catalonia (Spain), and to estimate the effect of thrombolysis on short and long-term survival. METHODS: From May 1992 to May 1993, all the patients with myocardial infarction admitted to the hospitals of the Costa de Ponent area in the first 72 hours after the initial symptoms were consecutively included in this prospective study. Information on pre-hospital phase, emergency room management and hospitalization was collected. All the patients discharged alive from hospital were followed up by telephone one and four years after hospital admission. RESULTS: 521 patients aged 74 years or less were included. Thrombolytic therapy was applied in 35.3%. There were no statistically significant differences in the proportion of thrombolysis between hospitals with or without intensive care or coronary units. Ten patients died in the emergency room; in the remaining cases, the 28-day case fatality was 10.0%. The effect of thrombolytic treatment on 28-day case fatality was estimated in a logistic regression model, after controlling for age, gender, Killip, ventricular arrhythmia and location of infarction (OR: 0.36; CI 95%: 0.15-0.88). In 28-day survivors, the 4-year cumulated probability of survival was 88.4%, being significantly higher in the group who had received thrombolytic therapy. CONCLUSIONS: In the population studied, 28-day case mortality of acute myocardial infarction is similar to that reported in other Mediterranean regions. The benefits of thrombolysis in the acute phase are found to persist after 4 years.

[Malignant pleural mesothelioma: clinical characteristics, prognostic factors and treatment]. / Mesotelioma maligno pleural. Características clínicas, factores pronósticos y tratamiento.

Malignant pleural mesothelioma soon leads to death no matter what type of treatment is provided. We discuss the clinical signs, prognostic factors and treatment given in 41 cases managed over the past 13 years in our oncology department. 32% had been exposed to asbestos, 61% were 60 years old or younger, 71% had a Karnofsky's index > or = 80% and 63% were stage I (Butchart). The first symptom leading to diagnosis was pain in 66% and mean time between first symptom and diagnosis was 3 months. Thirty patients never experienced full remission of disease: 15 were treated with palliative chemotherapy (CHT), 1 with palliative radiotherapy (RT), 5 with partial pleurectomy (PP) plus RT and/or CHT. Nine were given symptomatic treatment only. Only 11 (27%) patients experienced full remission after treatment: 7 had had extrapleural pneumonectomy, 2 had been given CHT and RT series and 4 had undergone PP with or without RT and/or CHT follow-up. Only 3 of these patients were still alive with no relapse more than 1 year later. Mean survival was 8 months. Univariate analysis revealed that the prognostic factors influencing survival were age and Karnofsky's index. Patients initially treated with surgery had a higher rate of survival. In conclusion, only Karnofsky's index and age were prognostic factors in our series. The better survival of patients initially treated surgically is probably related to prior screening.

The role of anxiety and adaptation to illness in the intensity of postchemotherapy nausea in cancer patients.

The aim of this work was to assess whether cancer patients presenting high anxiety levels or poor adaptation to cancer experience higher levels of postchemotherapy nausea, regardless of the emetogenicity of the chemotherapy schedule. Sixty-three patients were interviewed before receiving their chemotherapy schedule and some psychological variables were assessed. Nausea intensity was also assessed after treatment. The results showed that patients with relatively higher levels of nausea reported higher levels of anxiety prior to chemotherapy and lower levels of adaptation to cancer. Thus, evidence for a modulating effect of psychological factors in postchemotherapy emesis is suggested.

An update on molecularly targeted therapies in second- and third-line treatment in non-small cell lung cancer: focus on EGFR inhibitors and anti-angiogenic agents.

Docetaxel, pemetrexed and epidermal growth factor receptor tyrosine kinase inhibitors (gefitinib and erlotinib) are recommended second-line therapy for advanced non-small cell lung cancer (NSCLC) patients with disease progression. Although erlotinib is the only recommended third-line therapy, several drugs are being used in the clinic. Recent studies have focused on combining targeted agents with approved therapies, including broad-spectrum multikinase inhibitors targeting multiple ErbB Family receptors and multitargeted anti-angiogenic agents targeting the vascular endothelial growth factor receptor, platelet-derived growth factor receptor and fibroblast growth factor receptor pathways. Here, we review targeted therapies that are being evaluated in second- and third-line settings in NSCLC, including the ErbB Family Blocker afatinib (BIBW 2992), multityrosine kinase inhibitors (pelitinib [EKB-56]), neratinib [HKI-272], canertinib [CI-1033], lapatinib [GW-572016], dacomitinib [PF-299804]) and multitargeted anti-angiogenic agents (vandetanib [ZD6474], sunitinib [SU11248], sorafenib [BAY43-9006], nintedanib [BIBF1120], axitinib [AG-013736], cediranib [AZD2171], motesanib [AMG 706], linifanib [ABT869] and pazopanib [GW786034]).