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PURPOSE Gemcitabine monotherapy is the standard palliative chemotherapy for pancreatic adenocarcinoma. Gemcitabine requires plasma membrane nucleoside transporter proteins to efficiently enter cells and exert it cytotoxicity. In vitro studies have demonstrated that deficiency of human equilibrative nucleoside transporter 1 (hENT1), the most widely abundant(More)
BACKGROUND Dacomitinib is an irreversible pan-HER tyrosine-kinase inhibitor with preclinical and clinical evidence of activity in non-small-cell lung cancer. We designed BR.26 to assess whether dacomitinib improved overall survival in heavily pretreated patients with this disease. METHODS In this double-blind, randomised, placebo-controlled, phase 3(More)
MUC1 is a mucinous glycoprotein which is overexpressed and under or aberrantly glycosylated in many human malignancies. MUC1 is associated with cellular transformation and can confer resistance to genotoxic agents. L-BLP25 is a peptide vaccine strategy that targets the exposed core peptide of MUC1. In preclinical studies, L-BLP25 induced a cellular immune(More)
PURPOSE OF REVIEW Integrating targeted therapies against the epidermal growth factor receptor (EGFR) and angiogenesis pathways into standard treatment paradigms for advanced nonsmall cell lung cancer (NSCLC) have been successful, but not yet curative. Two treatment strategies, in development, seem particularly appealing for further study: insulin-like(More)
BACKGROUND Erlotinib is a key therapy for advanced NSCLC. Concurrent AS therapy with TKIs might reduce TKI plasma levels. Because of gastroesophageal reflux disease prevalence, this retrospective analysis was undertaken to determine if coadministering erlotinib with AS therapy affected NSCLC outcomes. PATIENTS AND METHODS Records of advanced NSCLC(More)
BACKGROUND Patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL) have an unfavourable prognosis with few treatment options. Polatuzumab vedotin is an antibody-drug conjugate containing an anti-CD79B monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin E. We aimed to assess the safety and clinical activity(More)
INTRODUCTION Epidermal growth factor receptor tyrosine kinase inhibitors given concurrently with chemotherapy do not improve patient outcomes compared with chemotherapy alone in advanced non-small cell lung cancer (NSCLC). On the basis of preclinical models, we hypothesized pharmacodynamic separation, achieved by intermittent delivery of epidermal growth(More)
INTRODUCTION Afatinib, an irreversible ErbB family blocker, demonstrated synergistic inhibition of epidermal growth factor receptor-mutant cell growth with pemetrexed. This phase I study investigated the maximum tolerated dose (MTD), safety, pharmacokinetics, and antitumor activity of afatinib plus pemetrexed in patients with advanced solid tumors. (More)
PURPOSE Activating mutations in the epidermal growth factor receptor (EGFR) are associated with enhanced response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC), whereas KRAS mutations translate into poor patient outcomes. We hypothesized that analysis of plasma for EGFR and KRAS mutations from shed tumor DNA would have clinical(More)
The cornerstone of treatment for early-stage non-small cell lung cancer (NSCLC) has long been surgical resection. Over the past few years, there has been a paradigm shift to provide adjuvant platinum-based chemotherapy for patients with completely resected stage II-IIIA NSCLC founded on large randomized clinical trials demonstrating longer overall survival(More)