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Gastric cancer is one of the most common types of cancer in the world, usually diagnosed at an advanced stage. Despite the advances in specific anticancer agents' development, the survival rates remain modest, even in early stages. HER2 overexpression was identified on 15% - 20% of gastric cancer patients. Trastuzumab-based chemotherapy provides obvious efficacy improving outcomes of HER2 positive gastric cancer patients. We performed a meta-analysis to estimate the efficacy of the addition of trastuzumab over chemotherapy. We identified randomized controlled trials (RCTs) which compare the addition of trastuzumab therapy to chemotherapy alone reporting progression-free survival (PFS), time to progression (TTP), overall survival (OS), and/or response rates as our eligible trials. Night trials including 1101 patients were eligible for analysis. Trastuzumab therapeutic partners were cisplatin (9 RCTs), 5-fluorouracil (8 RCTs), capecitabine (6 RCTs), irinotecan (1 RCTs), docetaxel (1 RCTs), oxaliplatin (1 RCTs), and leucovorin (1 RCTs). The addition of trastuzumab agents improved OS (HR = 0.80; 95% CI = 0.72 - 0.89), PFS (HR = 0.70; 95% CI = 0.59 - 0.83), TTP (HR = 0.69; 95% CI = 0.57 - 0.83), and overall response rate (RR = 1.22; 95% CI = 0.94 - 1.59), DCR (RR = 1.19; 95% CI = 1.10 - 1.28). Our meta-analysis affirmed the efficacy of adding trastuzumab agent to chemotherapy in HER2 positive gastric cancer.
Background: Skin is one the most important sites for administration of drugs to obtain desired pharmacological effects either locally or through systemic bioavailability; and this has placed the transdermal route of drug delivery as an attractive and as one of the most innovative areas for conducting drug delivery research. However the stratum corneum in skin creates hurdles and acts as significant barrier for the permeation of drugs through skin. Penetration enhancers play a pivotal role to overcome such barriers and help enhance the permeation of drug through skin. However, penetration enhancement technology is challenging development and needs to be properly and skillfully addressed. Objective: The present investigation aimed to study the penetration enhancing effect of a newly synthesized alcohol derivative of an acyclic monoterpene (Tetrahydrogeraniol-THG). Methodology: The new derivative, 5,9-Dimethyl-1-Decanol (DIMDOL), has been synthesized by a chemical reaction of the THG with Grignard reagent and ethylene oxide. Permeation enhancing effect of the synthesized derivative was explored for better transdermal penetration of the two model drugs viz. tramadol hydrochloride and 5-fluorouracil (5-FU) through the excised rat skin by conducting in-vitro permeation experiments employing Franz diffusion cells apparatus. The standard enhancers Azone and THG were used to compare penetration enhancing effect of the enhancers. Results: It was revealed that DIMDOL could effectively enhance the permeability of both the drugs by 18.60 and 73.19 folds across the skin used with a lag time of 3.35 and 1.20 h, respectively. The newly synthesized derivative was found to significantly increase the partition coefficient and diffusion coefficient values. Conclusion: The results obtained suggest that DIMDOL can more effectively enhance the permeation of these model drugs, expectedly by affecting the stratum corneum and interacting with both lipid-rich layers and keratin-rich layers of the excised rat skin.