Gemcitabine Plus Erlotinib for Advanced Pancreatic Cancer: A Systematic Review With Meta-Analysis.

Gemcitabine plus erlotinib for advanced pancreatic cancer: a systematic review with meta-analysis.

PLoS One. 2013; 8(3): e57528
Yang ZY, Yuan JQ, Di MY, Zheng DY, Chen JZ, Ding H, Wu XY, Huang YF, Mao C, Tang JL

BACKGROUND: This study aims to comprehensively summarize the currently available evidences on the efficacy and safety of gemcitabine plus erlotinib for treating advanced pancreatic cancer. METHODOLOGYPRINCIPAL FINDINGS: PubMed, EMBASE, The Cochrane Library and abstracts of recent major conferences were systematically searched to identify relevant publications. Studies that were conducted in advanced pancreatic cancer patients treated with gemcitabine plus erlotinib (with or without comparison with gemcitabine alone) and reporting objective response rate, disease control rate, progression-free survival, time-to-progression, overall survival, 1-year survival rate and/or adverse events were included. Data on objective response rate, disease control rate, 1-year survival rate and adverse events rate, respectively, were combined mainly by using Meta-Analyst software with a random-effects model. Data on progression-free survival, time-to-progression and overall survival were summarized descriptively. Sixteen studies containing 1,308 advanced pancreatic cancer patients treated with gemcitabine plus erlotinib were included. The reported median progression-free survival (or time-to-progression), median overall survival, 1-year survival rates, objective response rates and disease control rates were 2-9.6 months, 5-12.5 months, 20%-51%, 0%-28.6% and 25.0%-83.3%, respectively. The weighted 1-year survival rate, objective response rate and disease control rate based on studies reporting robust results were 27.9%, 9.1% and 57.0%, respectively. According to the studies with relevant data, the incidences of total and severe adverse events were 96.3% and 62.9%, respectively. The most frequently reported adverse events were leucopenia, rash, diarrhea, vomitting, neutropenia, thrombocytopenia, anaemia, stomatitis, drug-induced liver injury, fatigue and fever. Compared with gemcitabine alone, the progression-free survival and overall survival with gemcitabine plus erlotinib were significantly longer, but there were also more deaths and interstitial lung disease-like syndrome related to this treatment. CONCLUSIONSSIGNIFICANCE: Gemcitabine plus erlotinib represent a new option for the treatment of advanced pancreatic cancer, with mild but clinically meaningful additive efficacy compared with gemcitabine alone. Its safety profile is generally acceptable, although careful management is needed for some specific adverse events. HubMed – drug


Malaria burden and artemisinin resistance in the mobile and migrant population on the thai-myanmar border, 1999-2011: an observational study.

PLoS Med. 2013 Mar; 10(3): e1001398
Carrara VI, Lwin KM, Phyo AP, Ashley E, Wiladphaingern J, Sriprawat K, Rijken M, Boel M, McGready R, Proux S, Chu C, Singhasivanon P, White N, Nosten F

The Shoklo Malaria Research Unit has been working on the Thai-Myanmar border for 25 y providing early diagnosis and treatment (EDT) of malaria. Transmission of has declined, but resistance to artesunate has emerged. We expanded malaria activities through EDT and evaluated the impact over a 12-y period.Between 1 October 1999 and 30 September 2011, the Shoklo Malaria Research Unit increased the number of cross-border (Myanmar side) health facilities from two to 11 and recorded the number of malaria consultations. Changes in malaria incidence were estimated from a cohort of pregnant women, and prevalence from cross-sectional surveys. In vivo and in vitro antimalarial drug efficacy were monitored. Over this period, the number of malaria cases detected increased initially, but then declined rapidly. In children under 5 y, the percentage of consultations due to malaria declined from 78% (95% CI 76-80) (1,048/1,344 consultations) to 7% (95% CI 6.2-7.1) (767/11,542 consultations), 0.001. The ratio of declined from 1.4 (95% CI 1.3-1.4) to 0.7 (95% CI 0.7-0.8). The case fatality rate was low (39/75,126; 0.05% [95% CI 0.04-0.07]). The incidence of malaria declined from 1.1 to 0.1 episodes per pregnant women-year. The cumulative proportion of decreased significantly from 24.3% (95% CI 21.0-28.0) (143/588 pregnant women) to 3.4% (95% CI 2.8-4.3) (76/2,207 pregnant women), 0.001. The in vivo efficacy of mefloquine-artesunate declined steadily, with a sharp drop in 2011 (day-42 PCR-adjusted cure rate 42% [95% CI 20-62]). The proportion of patients still slide positive for malaria at day 3 rose from 0% in 2000 to reach 28% (95% CI 13-45) (8/29 patients) in 2011.Despite the emergence of resistance to artesunate in , the strategy of EDT with artemisinin-based combination treatments has been associated with a reduction in malaria in the migrant population living on the Thai-Myanmar border. Although limited by its observational nature, this study provides useful data on malaria burden in a strategically crucial geographical area. Alternative fixed combination treatments are needed urgently to replace the failing first-line regimen of mefloquine and artesunate. Please see later in the article for the Editors’ Summary. HubMed – drug


Evaluation of drug-resistant Enterobacteriaceae in retail poultry and beef.

Poult Sci. 2013 Apr; 92(4): 1098-107
Kilonzo-Nthenge A, Rotich E, Nahashon SN

There has been increasing concern on the emergence of multidrug-resistant foodborne pathogens from foods of animal origin, including poultry. The current study aimed to evaluate antibiotic-resistant Enterobacteriaceae from raw retail chicken/turkey parts (thigh, wings, breast, and ground) and beef meat (ground and chunks) in Middle Tennessee. Resistance of the collected Enterobacteriaceae to a panel of antibiotics was determined by the Kirby-Bauer disk diffusion test. Retail meats were also assayed for the presence of Salmonella spp. and Escherichia coli O157:H7. Two hundred thirty-seven samples representing 95.2% of the total of 249 samples tested were positive for Enterobacteriaceae. The level of contamination with Enterobacteriaceae in raw meats ranged from 3.26 log cfu/g to 4.94 log cfu/g with significant differences in counts among meat types (P < 0.05). Contamination was significantly greater (P < 0.05) in ground beef, beef chucks, ground chicken, chicken breast, and turkey wings (4.92, 4.58, 4.94, 4.75, 4.13 log cfu/g, respectively) than ground turkey and chicken wings (3.26 and 3.26 log cfu/g, respectively). Klebsiella oxytoca, Serratia spp., E. coli, and Haffnia alvei were most prevalent contaminants at 27.4, 14.3, 12.1, and 11.4%, respectively. Resistance of the Enterobacteriaceae to antimicrobials was most frequent with erythromycin, penicillin, and ampicillin at 100, 89, and 65.8%, respectively. Few (2.7%) of the Enterobacteriaceae were resistant to chloramphenicol. Salmonella spp., E. coli O157:H7, Morganella morganii, Yersinia enterocolitica, and Vibrio parahemolyticus exhibited multiple drug resistance. This investigation demonstrates that raw poultry and beef are potential reservoirs of antibiotic-resistant Enterobacteriaceae. HubMed – drug