Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: phase III randomized LUX-Lung 5 trial.

BACKGROUND: Afatinib has demonstrated clinical benefit in patients with non-small-cell lung cancer progressing after treatment with erlotinib/gefitinib. This phase III trial prospectively assessed whether continued irreversible ErbB-family blockade with afatinib plus paclitaxel has superior outcomes versus switching to chemotherapy alone in patients acquiring resistance to erlotinib/gefitinib and afatinib monotherapy. PATIENTS AND METHODS: Patients with relapsed/refractory disease following ≥1 line of chemotherapy, and whose tumors had progressed following initial disease control (≥12 weeks) with erlotinib/gefitinib and thereafter afatinib (50 mg/day), were randomized 2:1 to receive afatinib plus paclitaxel (40 mg/day; 80 mg/m(2)/week) or investigator's choice of single-agent chemotherapy. The primary end point was progression-free survival (PFS). Other end points included objective response rate (ORR), overall survival (OS), safety and patient-reported outcomes. RESULTS: Two hundred and two patients with progressive disease following clinical benefit from afatinib were randomized to afatinib plus paclitaxel (n = 134) or single-agent chemotherapy (n = 68). PFS (median 5.6 versus 2.8 months, hazard ratio 0.60, P = 0.003) and ORR (32.1% versus 13.2%, P = 0.005) significantly improved with afatinib plus paclitaxel. There was no difference in OS. Global health status/quality of life was maintained with afatinib plus paclitaxel over the entire treatment period. The median treatment duration was 133 and 51 days with afatinib plus paclitaxel and single-agent chemotherapy, respectively; 48.5% of patients receiving afatinib plus paclitaxel and 30.0% of patients receiving single-agent chemotherapy experienced drug-related grade 3/4 adverse events. Treatment-related adverse events were consistent with those previously reported with each agent. CONCLUSION: Afatinib plus paclitaxel improved PFS and ORR compared with single-agent chemotherapy in patients who acquired resistance to erlotinib/gefitinib and progressed on afatinib after initial benefit. LUX-Lung 5 is the first prospective trial to demonstrate the benefit of continued ErbB targeting post-progression, versus switching to single-agent chemotherapy. TRIAL REGISTRATION NUMBER: NCT01085136 (clinicaltrials.gov).

Dengue fever mimicking acute appendicitis: A case report.

INTRODUCTION: Dengue fever is an acute viral disease, which usually presents as a mild febrile illness. Patients with severe disease present with dengue haemorrhagic fever or dengue toxic shock syndrome. Rarely, it presents with abdominal symptoms mimicking acute appendicitis. We present a case of a male patient presenting with right iliac fossa pain and suspected acute appendicitis that was later diagnosed with dengue fever following a negative appendicectomy. PRESENTATION OF CASE: A 13-year old male patient presented with fever, localized right-sided abdominal pain and vomiting. Abdominal ultrasound was not helpful and appendicectomy was performed due to worsening abdominal signs and an elevated temperature. A normal appendix with enlarged mesenteric nodes was found at surgery. Complete blood count showed thrombocytopenia with leucopenia. Dengue fever was now suspected and confirmed by IgM enzyme-linked immunosorbent assay against dengue virus. DISCUSSION: This unusual presentation of dengue fever mimicking acute appendicitis should be suspected during viral outbreaks and in patients with atypical symptoms and cytopenias on blood evaluation in order to prevent unnecessary surgery. CONCLUSION: This case highlights the occurrence of abdominal symptoms and complications that may accompany dengue fever. Early recognition of dengue fever mimicking acute appendicitis will avoid non-therapeutic operation and the diagnosis may be aided by blood investigations indicating a leucopenia, which is uncommon in patients with suppurative acute appendicitis.

Isolation and characterization of 15 polymorphic microsatellite DNA loci from Argyrosomus japonicus (mulloway), a new aquaculture species in Australia.

Fifteen microsatellite loci were isolated for population genetic studies of mulloway (Argyrosomus japonicus), a commercial/recreational fish species in Southern Australia. A genomic library was screened randomly for di- tri- and tetranucleotide repeats. Fifteen microsatellite marker loci were developed that were highly polymorphic (allele number ranged from four to 18). Observed and expected heterozygosities ranged from 0.17 to 1 and from 0.27 to 0.91, respectively. These markers have proven useful for estimating genetic variation and for evaluating population structure across the species' natural distribution. They also provide powerful tools for optimizing hatchery practices to conserve genetic diversity.