Biologics in combination with chemotherapy for gastric cancer: is this the answer?

Gastric cancer (GC) continues to be a significant problem worldwide and is the third leading cause of cancer death. Armamentarium to treat GC whether it is potentially curable or metastatic (incurable) has changed little over the last decades with only two new agents being approved (trastuzumab and ramucirumab). Many relatively healthy patients after second-line therapy have limited and generally ineffective options. The recent The Cancer Genome Atlas analysis has uncovered four genotypes of GC; however, it is not sufficient to change our treatment strategies and more work needs to be done. The popular front-line regimen containing a platinum compound and a fluoropyrimidine is widely used for drug development and has worked well globally. Thus, this combination appears suitable for adding a biologic agent. The search for new classes of cytotoxics has almost stopped, but it is clear that cytotoxic therapy continues to contribute and it is here to stay. Biologic agents that modulate the immune system of the host appear promising along with many other biologics that can potentially inhibit signaling pathways that are often employed by GC cells. We will briefly describe the efforts that have targeted EGFR, mTOR, angiogenesis and MET pathways.     

Hypoproteinemia in the second trimester among patients with preeclampsia prior to the onset of clinical symptoms

Objective: To find a risk factor for “uncomplicated” preeclampsia (PE) comparing blood biochemical parameters between women with uncomplicated PE and healthy pregnant women in each trimester of pregnancy. Methods: A retrospective study was performed on 83 cases of uncomplicated PE, selected from 434 patients with PE, disregarding subjects with other complications relevant to hypertension during pregnancy. The study was limited to women with PE occurring in the third trimester, and records of blood biochemical parameters were evaluated. Controls were recruited from 108 healthy volunteers with normal singleton pregnancies. Results: A significant decrease in total protein was observed in the uncomplicated PE group in the second trimester prior to the onset of clinical symptoms. Conclusion: Hypoproteinemia during pregnancy may be a risk factor for this pathophysiology, and the maintenance of sufficient protein in early pregnancy could contribute to prophylaxis for women with uncomplicated PE.     

Analysis of regulatory review times of new drugs in Japan: association with characteristics of new drug applications,regulatory agency,and pharmaceutical companies

What is known and Objective: Various factors have been reported to be associated with the duration of regulatory review of new drug applications (NDAs). We investigated potential links between the review times in Japan and the attributes of NDAs, the regulatory agency and pharmaceutical companies. Methods: We analysed new drugs approved in 2000–2009 in Japan using a proprietary database collected through annual surveys to pharmaceutical companies. Regression models in which individual firms were treated as either a fixed effect or a random effect were applied to examine factors associated with the overall review time and the duration of each step of the review. Results and Discussion: The fixed effect model analysis using variations within each firm indicated that new molecular entities that were submitted to the Pharmaceuticals and Medical Devices Agency (PMDA), priority reviews and pre‐NDA consultations were associated with a shorter overall review time, whereas additional studies during the review resulted in a longer review. In the random effect model analysis using both within‐ and between‐firm variations, use of end‐of‐phase 2 consultations and foreign clinical data also had negative coefficients, suggesting the effect of these two vary among firms. Analysis of each step of the review process revealed NDAs reviewed by the Committee on Drugs under the Ministry of Health, Labour and Welfare, and the number of NDAs assigned to a review team were significantly linked with their duration, whereas consultation services and the number of reviewers had no relation. What is new and Conclusion: Factors associated with each step of the review process as well as the differences in attributes and strategies among pharmaceutical companies should be considered to further improve the speed, quality and efficiency of the regulatory review.