Citations

228 Background: Even though gemcitabine monotherapy is commonly used as first-line treatment for metastatic pancreatic cancer, many novel treatment approaches have focused on combination chemotherapy. FOLFIRINOX, a combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin, has recently been shown to improve survival compared to gemcitabine. However, it is unclear whether survival benefits are counterbalanced by a poor quality of life due to the adverse effects. The aim of this study was to review emerging strategies that enhance treatment of patients with metastatic pancreatic cancer. Methods: Two authors independently conducted a comprehensive search of the Cochrane library PUBMED, and published proceedings from major oncologic and gastrointestinal cancer meetings from January 1980 to July 2012. Only published randomized controlled trials were eligible for inclusion. Our primary outcome measures were: progression-free survival (PFS), overall survival (OS) and serious adverse events (grade 3 or 4). Results: Thirty-one studies involving 7,957 patients were included in the analysis. There was an overall statistically significant increase in OS (RR 1.10, 95% CI 1.03-1.30) and PFS (RR 1.27, 95% CI 1.14-1.46) for the gemcitabine-based combination therapy group versus the gemcitabine monotherapy group. Subgroup analysis showed that only patients with fluoropyrimidine and platinum containing regimens showed prolonged survival: RR 1.33, 95% CI 1.04-1.76 and RR 1.38, 95% CI 1.08-1.76, respectively. The most common severe adverse event (neutropenia) was found in 45% of patients treated with FOLFIRINOX. Conclusions: Overall, gemcitabine in combination with fluoropyrimidine or platinum containing regimens can improve overall survival in patients with metastatic pancreatic cancer compared to gemcitabine alone. Even though, FOLFIRINOX therapy is associated with better survival outcomes than gemcitabine, the prolonged survival comes at the cost of poorer quality of life due to a higher incidence of adverse events. More data is needed from studies involving novel combination therapy such as hedgehog pathway inhibitors and radio-immunotherapy.

AbstractBackground & AimsAntiviral drugs are safe and effective in the third trimester to prevent intrauterine transmission of hepatitis B virus, and are recommended for hepatitis B virus (HBV) infected gravid mothers (between weeks 28 and 32) with high viral load, followed by postnatal hepatitis B immunization in the newborn. We estimated the comparative efficacy of antiviral drugs for prevention of vertical transmission of HBV, through a network meta‐analysis of clinical trials.MethodsWe conducted a comprehensive search of MEDLINE, EMBASE and published proceedings from major liver meetings from January 1980 to November 2014. We conducted pair‐wise meta‐analyses and Bayesian framework using Markov chain Monte Carlo methods, combining direct and indirect evidence for any given pair of treatments.ResultsSeventeen clinical trials involving 2764 newborns of hepatitis B surface antigen seropositive mothers were eligible for analysis. There were no clinical trials involving tenofovir or entecavir. On pair‐wise meta‐analyses, telbivudine (hazard ratio, HR 0.12, 95% confidence interval (CI) 0.04–0.37; I2 = 0%), and Lamivudine (HR 0.40, 95% CI 0.24–0.65; I2 = 0%), were more effective than placebo in reducing vertical transmission of HBV in high viremic hepatitis B e antigen (HBeAg)‐positive chronic Hepatitis B Chinese patients. Sensitivity analyses limited to studies with HBeAg seropositive mothers revealed similar results.ConclusionsBased on a Bayesian network meta‐analysis of clinical trials, combining direct and indirect treatment comparisons, telbivudine appears to be more effective than Lamivudine for preventing vertical transmission of HBV infection. Trials assessing the efficacy of tenofovir or entecavir compared to placebo or other antiviral drugs are lacking.

The rise in incidence of hepatocellular carcinoma (HCC) in the United States has been well documented. The purpose of this analysis was to examine temporal trends in HCC incidence, mortality, and survival within the U.S. population. The Surveillance, Epidemiology, and End Results data were used to examine incidence and incidence‐based (IB) mortality in HCC from 1973 to 2011. Secular trends in age‐adjusted incidence and IB mortality by sex and cancer stage were characterized using the Joinpoint Regression program. In 1973, HCC incidence was 1.51 cases per 100,000, whereas in 2011, HCC incidence was 6.20 cases per 100,000. Although HCC incidence continues to increase, a slowing of the rate of increase occurs around 2006. In a sensitivity analysis, there was no significant increase in incidence and IB mortality from 2009 to 2011. There was a significant increase in overall median survival from the 1970s to 2000s (2 vs. 8 months; P < 0.001). On multivariable Cox's regression analysis, age, sex, race, tumor grade, stage at diagnosis, lymph/vascular invasion, number of primary tumors, tumor size, and liver transplant were independently associated with mortality. Conclusion: Our results indicate a deceleration in the incidence of HCC around 2006. Since 2009 and for the first time in four decades, there is no increase in IB mortality and incidence rates for HCC in the U.S. population. The nonsignificant increase in incidence and IB mortality in recent years suggest that the peak of the HCC epidemic may be near. A significant survival improvement in HCC was also noted from 1973 to 2010, which seems to be driven by earlier detection of HCC at a curative stage and greater utilization of curative modalities (especially transplant). (Hepatology 2015;61:191–199)