Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used medication in several countries, including Thailand. NSAIDs have been associated with hepatic side effects; however, the frequency of these side effects is uncertain. Aim of the Review To systematically review published literature on randomized, controlled trials that assessed the risk of clinically significant hepatotoxicity associated with NSAIDs. Methods Searches of bibliographic databases EMBASE, PubMed, and the Cochrane Library were conducted up to July 30, 2016, to identify randomized controlled trials of ibuprofen, naproxen, diclofenac, piroxicam, meloxicam, mefenamic acid, indomethacin, celecoxib, and etoricoxib in adults with any disease that provide information on hepatotoxicity outcomes. Results Among the 698 studies, 18 studies met the selection criteria. However, only 8 studies regarding three NSAIDs (celecoxib, etoricoxib, and diclofenac) demonstrated clinically significant hepatotoxic evidence based on hepatotoxicity justification criteria. Of all the hepatotoxicity events found from the above-mentioned three NSAIDs, diclofenac had the highest proportion, which ranged from 0.015 to 4.3 (×10−2), followed by celecoxib, which ranged from 0.13 to 0.38 (×10−2), and etoricoxib, which ranged from 0.005 to 0.930 (×10−2). Conclusion Diclofenac had higher rates of hepatotoxic evidence compared to other NSAIDs. Hepatotoxic evidence is mostly demonstrated as aminotransferase elevation, while liver-related hospitalization or discontinuation was very low.

Cisplatin-based chemotherapy frequently resulted in acquired resistance of cancer cells. The underlying mechanism of such resistance is not fully understood especially the involvement of autophagy and autophagic cell death. This study thus investigated whether an alteration in autophagy could be responsible for cisplatin resistance in the long-term exposure lung carcinoma cells. The cisplatin resistant clone (H460/cis) of H460 cells was established by exposing the cells with gradually increasing concentrations of cisplatin until chemoresistance acquisition was elucidated by MTT, Hoechst 33342 staining and comet assays. Degree of autophagosome formation and level of LC3 marker were evaluated by acridine orange and western blot analysis, respectively. H460/cis cells exhibited irregular shape with ~3-fold resistant to cisplatin-induced apoptosis compared with H460 cells. Proteins analysis for LC3 indicated that the levels of LC3 in resistant cells were significantly lower than those in H460 cells. Moreover, autophagosome formation detected by acridine orange staining was dramatically reduced in the resistant cells, suggesting the role of autophagy in attenuating of cisplatin-induced cell death. Further, co-treatment of cisplatin with autophagy inducer, trifluorperazine, could resensitize H460/cis cells to cisplatin-induced cell death. Our findings reveal the novel mechanisms causing cisplatin resistance in lung carcinoma cells after long-term drug exposure regarding autophagy.

Objective: To assess the cost-effectiveness of first-line chemotherapy regimens for non-small cell lung cancer patients in Thailand.Methods: A Markov model comprising 3 health states (progression-free survival, progression, death) was used to estimate the long-term costs and health outcomes under a societal perspective with a lifetime horizon. Intervention was the combination of pemetrexed and cisplatin, AND the comparators were gemcitabine plus cisplatin and carboplatin plus paclitaxel. The efficacy and toxicity were obtained from landmark clinical trials, and the costs were based on a local Thai database. All costs and outcomes were discounted at 3%. The findings were reported as incremental cost-effectiveness ratios (ICERs) in both Thai baht (THB) and USD per quality-adjusted life year (QALY) gained. A series of sensitivity analyses, including 1way and probabilistic sensitivity analyses, were performed. A cost-effectiveness acceptability curve was generated with a threshold of 160 000 THB/QALY or 4987 USD/QALY.Results: Under the base-case analysis, pemetrexed plus cisplatin had the greatest total cost among 3 regimens, yielding an ICER of 64 369.97 USD/QALY (2 064 989 THB/QALY) compared with gemcitabine plus cisplatin, and ICER of 8649.16 USD/ QALY (277 465 THB/QALY) compared with carboplatin plus paclitaxel. The probabilistic sensitivity analysis results indicated that at the local Thai threshold, gemcitabine plus cisplatin was likely to be the most cost-effective regimen.Conclusions: At the current price of pemetrexed, the combination of pemetrexed plus cisplatin was not found to be a costeffective first-line regimen for patients with non-small cell lung cancer at the local Thai threshold compared with the gemcitabine plus cisplatin and carboplatin plus paclitaxel regimens.