A Randomized Phase II Study of Metformin plus Paclitaxel/Carboplatin/Bevacizumab in Patients with Chemotherapy-Naïve Advanced or Metastatic Nonsquamous Non-Small Cell Lung Cancer.

Background: In the absence of a targeted oncogenic driver mutation or high programmed death-ligand 1 expression, systemic therapy with platinum-based doublet chemotherapy with or without bevacizumab has been the standard treatment in advanced or metastatic non-small cell lung cancer (NSCLC). Metformin has been shown to have antitumor effects via a variety of insulin-dependent and insulin-independent mechanisms and to be potentially synergistic with chemotherapy.

Materials And Methods: This open-label single-center phase II study (NCT01578551) enrolled patients with chemotherapy-naïve advanced or metastatic nonsquamous NSCLC and randomized them (3:1) to receive carboplatin, paclitaxel, and bevacizumab with (Arm A) or without (Arm B) concurrent metformin for four to six cycles followed by maintenance therapy with bevacizumab ± metformin continued until disease progression, intolerable toxicity, or study withdrawal.

Hepatitis C - Assessment to Treatment Trial (HepCATT) in primary care: study protocol for a cluster randomised controlled trial.

Background: Public Health England (PHE) estimates that there are upwards of 160,000 individuals in England and Wales with chronic hepatitis C virus (HCV) infection, but until now only around 100,000 laboratory diagnoses have been reported to PHE and of these 28,000 have been treated. Targeted case-finding in primary care is estimated to be cost-effective; however, there has been no robust randomised controlled trial evidence available of specific interventions. Therefore, this study aims to develop and conduct a complex intervention within primary care and to evaluate this approach using a cluster randomised controlled trial.

Problem drug use prevalence estimation revisited: heterogeneity in capture-recapture and the role of external evidence.

Background And Aims: Capture-recapture (CRC) analysis is recommended for estimating the prevalence of problem drug use or people who inject drugs (PWID). We aim to demonstrate how naive application of CRC can lead to highly misleading results, and to suggest how the problems might be overcome.

Methods: We present a case study of estimating the prevalence of PWID in Bristol, UK, applying CRC to lists in contact with three services.

Combination epigenetic therapy has efficacy in patients with refractory advanced non-small cell lung cancer.

Unlabelled: Epigenetic alterations are strongly associated with the development of cancer. We conducted a phase I/II trial of combined epigenetic therapy with azacitidine and entinostat, inhibitors of DNA methylation and histone deacetylation, respectively, in extensively pretreated patients with recurrent metastatic non-small cell lung cancer. This therapy is well tolerated, and objective responses were observed, including a complete response and a partial response in a patient who remains alive and without disease progression approximately 2 years after completing protocol therapy.

Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449.

Medulloblastoma is the most common malignant brain tumor in children. Aberrant activation of the hedgehog signaling pathway is strongly implicated in the development of some cases of medulloblastoma. A 26-year-old man with metastatic medulloblastoma that was refractory to multiple therapies was treated with a novel hedgehog pathway inhibitor, GDC-0449; treatment resulted in rapid (although transient) regression of the tumor and reduction of symptoms.

Assessing IDU prevalence and health consequences (HCV, overdose and drug-related mortality) in a primary care trust: implications for public health action.

Background: We report on an exercise to estimate the prevalence of injecting drug use (IDU) and associated harms in a single primary care trust.

Methods: Covariate capture-recapture methods to estimate (i) IDU prevalence; respondent driven sampling to measure (ii) prevalence of HCV and HIV and record linkage to measure (iii) mortality risk.

Results: (i) The overall estimated number of IDU was 5540 (95% confidence interval, CI: 4710-6780) for all cases and 3280 (95% CI: 1940-4610) for cases matched to primary care register, i.

A phase II tolerability study of cisplatin plus docetaxel as adjuvant chemotherapy for resected non-small cell lung cancer.

Introduction: We undertook this phase II study to measure postoperative drug delivery and toxicity of cisplatin plus docetaxel in patients with resected stage I-III non-small cell lung cancer.

Methods: The primary endpoint was amount of cisplatin delivered over a planned four cycles of adjuvant chemotherapy. Statistical design required a cohort to close if the regimen proved unlikely to improve cisplatin delivery compared with published phase III data.

Relative contribution of genetic and nongenetic modifiers to intestinal obstruction in cystic fibrosis.

Background & Aims: Neonatal intestinal obstruction (meconium ileus [MI]) occurs in 15% of patients with cystic fibrosis (CF). Our aim was to determine the relative contribution of genetic and nongenetic modifiers to the development of this major complication of CF.

Methods: A total of 65 monozygous twin pairs, 23 dizygous twin/triplet sets, and 349 sets of siblings with CF were analyzed for MI status, significant covariates, and genome-wide linkage.