Oral vinorelbine and cisplatin with concomitant radiotherapy in stage III non-small cell lung cancer (NSCLC): A feasibility study

Background: Concurrent chemoradiotherapy has improved survival in inoperable stage III non-small cell lung cancer (NSCLC). This phase I trial was performed in order to establish a dose recommendation for oral vinorelbine in combination with cisplatin and simultaneous radiotherapy. Patients and Methods: Previously untreated patients with stage IIIB NSCLC received concurrent chemoradiotherapy with 66 Gy and 2 cycles of cisplatin and oral vinorelbine which was administered at 3 different levels (40, 50 and 60 mg/m(2)). This was to be followed by 2 cycles of cisplatin/vinorelbine oral consolidation chemotherapy. The study goal was to determine the maximal recommended dose of oral vinorelbine during concurrent treatment. Results: 11 stage IIIB patients were entered into the study. The median radiotherapy dose was 66 Gy. Grade 3-4 toxicity included neutropenia, esophagitis, gastritis and febrile neutropenia. The dose-limiting toxicity for concurrent chemoradiotherapy was esophagitis. 9 patients received consolidation chemotherapy, with neutropenia and anemia/thrombocytopenia grade 3 being the only toxicities. The overall response was 73%. Conclusion: Oral vinorelbine 50 mg/m(2) (days 1, 8, 15 over 4 weeks) in combination with cisplatin 20 mg/m2 (days 1-4) is the recommended dose in combination with radiotherapy (66 Gy) and will be used for concurrent chemoradiotherapy in a forthcoming phase III trial testing the efficacy of consolidation chemotherapy in patients not progressing after chemoradiotherapy

Safety and feasibility of switching from phenytoin to levetiracetam monotherapy for glioma-related seizure control following craniotomy: a randomized phase II pilot study

Seizures are common in patients with gliomas, and phenytoin (PHT) is frequently used to control tumor-related seizures. PHT, however, has many undesirable side effects (SEs) and drug interactions with glioma chemotherapy. Levetiracetam (LEV) is a newer antiepileptic drug (AED) with fewer SEs and essentially no drug interactions. We performed a pilot study testing the safety and feasibility of switching patients from PHT to LEV monotherapy for postoperative control of glioma-related seizures. Over a 13-month period, 29 patients were randomized in a 2:1 ratio to initiate LEV therapy within 24 h of surgery or to continue PHT therapy. 6 month follow-up data were available for 15 patients taking LEV and for 8 patients taking PHT. In the LEV group, 13 patients (87%) were seizure-free. In the PHT group, 6 patients (75%) were seizure-free. Reported SEs at 6 months was as follows (%LEV/%PHT group): dizziness (0/14), difficulty with coordination (0/29), depression (7/14) lack of energy or strength (20/43), insomnia (40/43), mood instability (7/0). The pilot data presented here suggest that it is safe to switch patients from PHT to LEV monotherapy following craniotomy for supratentorial glioma. A large-scale, double-blinded, randomized control trial of LEV versus PHT is required to determine seizure control equivalence and better assess differences in SEs

Increased level of chromosomal damage after irradiation of lymphocytes from BRCA1 mutation carriers

Deleterious mutations in the BRCA1 gene predispose women to an increased risk of breast and ovarian cancer. Many functional studies have suggested that BRCA1 has a role in DNA damage repair and failure in the DNA damage response pathway often leads to the accumulation of chromosomal aberrations. Here, we have compared normal lymphocytes with those heterozygous for a BRCA1 mutation. Short-term cultures were irradiated (8Gy) using a high dose rate and subsequently metaphases were analysed by 24-colour chromosome painting (M-FISH). We scored the chromosomal rearrangements in the metaphases from five BRCA1 mutation carriers and from five noncarrier control samples 6 days after irradiation. A significantly higher level of chromosomal damage was detected in the lymphocytes heterozygous for BRCA1 mutations compared with normal controls; the average number of aberrations per mitosis was 3.48 compared with 1.62 in controls (P=0.0001). This provides new evidence that heterozygous mutation carriers have a different response to DNA damage compared with noncarriers and that BRCA1 has a role in DNA damage surveillance. Our finding has implications for treatment and screening of BRCA1 mutation carriers using modalities that involve irradiation

Prophylactic cranial irradiation in locally advanced non-small cell lung cancer: outcome of recursive partitioning analysis group 1 patients

<p>Abstract</p> <p>Background</p> <p>Prophylactic cranial irradiation (PCI) has been demonstrated to reduce or delay the incidence of brain metastases (BM) in locally advanced non-small cell lung carcinoma (LA-NSCLC) patients with various prognostic groups. With this current cohort we planned to evaluate the potential usefulness of prophylactic cranial irradiation (PCI) specifically in recursive partitioning analysis (RPA) Group 1, which is the most favorable group of LA-NSCLC patients.</p> <p>Methods</p> <p>Between March 2007 and February 2008, 62 patients in RPA group 1 were treated with sequential chemoradiotherapy and PCI for stage IIIB NSCLC. The induction chemotherapy consisted of 3 courses of cisplatin (80 mg/m²) and docetaxel (80 mg/m²); each course was given every 21 days. Thoracic radiotherapy (TRT) was given at a dose of 60 Gy using 3-D conformal planning. All patients received a total dose of 30 Gy PCI (2 Gy/fr, 5 days a week), beginning on the first day of the TRT. Then, all patients received 3 further courses of the same chemotherapy protocol.</p> <p>Results</p> <p>Six (9.7%) patients developed brain metastases during their clinical course. Only one (2%) patient developed brain metastasis as the site of first treatment failure. Median brain metastasis-free survival, overall survival, and progression free survival were 16.6, 16.7, and 13.0 months, respectively. By univariate analysis, rates of BM were significantly higher in patients younger than 60 years of age (p = 0.03). Multivariate analysis showed no significant difference in BM-free survival according to gender, age, histology, and initial T- and N-stage.</p> <p>Conclusion</p> <p>The current finding of almost equal bone metastasis free survival and overall survival in patients with LA-NSCLC in RPA group 1 suggests a longer survival for patients who receive PCI, and thereby have a reduced risk of BM.</p

A review of elliptical and disc galaxy structure, and modern scaling laws

A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their models to describe the radial distribution of stars in `nebulae'. This article reviews the progress since then, providing both an historical perspective and a contemporary review of the stellar structure of bulges, discs and elliptical galaxies. The quantification of galaxy nuclei, such as central mass deficits and excess nuclear light, plus the structure of dark matter halos and cD galaxy envelopes, are discussed. Issues pertaining to spiral galaxies including dust, bulge-to-disc ratios, bulgeless galaxies, bars and the identification of pseudobulges are also reviewed. An array of modern scaling relations involving sizes, luminosities, surface brightnesses and stellar concentrations are presented, many of which are shown to be curved. These 'redshift zero' relations not only quantify the behavior and nature of galaxies in the Universe today, but are the modern benchmark for evolutionary studies of galaxies, whether based on observations, N-body-simulations or semi-analytical modelling. For example, it is shown that some of the recently discovered compact elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to appear in "Planets, Stars and Stellar Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references incl. many somewhat forgotten, pioneer papers. Original submission to Springer: 07-June-201

Prognostic factors affecting long-term outcomes in patients with resected stage IIIA pN2 non-small-cell lung cancer: 5-year follow-up of a phase II study

The aim was to investigate the efficacy of neoadjuvant docetaxel–cisplatin and identify prognostic factors for outcome in locally advanced stage IIIA (pN2 by mediastinoscopy) non-small-cell lung cancer (NSCLC) patients. In all, 75 patients (from 90 enrolled) underwent tumour resection after three 3-week cycles of docetaxel 85 mg m−2 (day 1) plus cisplatin 40 or 50 mg m−2 (days 1 and 2). Therapy was well tolerated (overall grade 3 toxicity occurred in 48% patients; no grade 4 nonhaematological toxicity was reported), with no observed late toxicities. Median overall survival (OS) and event-free survival (EFS) times were 35 and 15 months, respectively, in the 75 patients who underwent surgery; corresponding figures for all 90 patients enrolled were 28 and 12 months. At 3 years after initiating trial therapy, 27 out of 75 patients (36%) were alive and tumour free. At 5-year follow-up, 60 and 65% of patients had local relapse and distant metastases, respectively. The most common sites of distant metastases were the lung (24%) and brain (17%). Factors associated with OS, EFS and risk of local relapse and distant metastases were complete tumour resection and chemotherapy activity (clinical response, pathologic response, mediastinal downstaging). Neoadjuvant docetaxel–cisplatin was effective and tolerable in stage IIIA pN2 NSCLC, with chemotherapy contributing significantly to outcomes