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GSK458 - Tips On How Along with Why You Also Can Gain Advantage Out Of It

10 In this study, median OS and median TTP were prolonged by nearly 3 months in the sorafenib group compared with the placebo group; median OS was 10.7 months versus 7.9 months (P<.001), and median TTP was 5.5 months versus 2.8 months (P<.001). Although sorafenib was shown to <a href="http://www.selleckchem.com/products/gsk2126458.html">www.selleckchem.com be effective, no patient had a CR, only 2% had a PR, and 71% had SD according to RECIST criteria. Recently, despite its effect on survival and TTP, in a draft guidance the National Institute for Health and Clinical Excellence suggested that sorafenib would not be a cost-effective first-line drug to treat advanced HCC.18 Also, the drug is indicated for treatment only in patients with preserved liver function (Child-Pugh A), at least in Italy. Before the evidence of efficacy of sorafenib GBA3 become available, conventional doxorubicin was among the most used and active agents in advanced HCC, with a response rate of approximately 25%.7 In a randomized study,6 free doxorubicin has been shown to be superior to palliative treatment of HCC, although a subsequent meta-analysis showed no efficacy of the drug in terms of survival.17 Conversely, the clinical usefulness of doxorubicin is limited by unacceptable toxicity, such as cardiotoxicity and myelosuppression, which may preclude adequate dosing. To decrease its toxicity, new formulations have been created, including pegylated liposomal doxorubicin. This drug has shown efficacy in advanced HCC, with a response rate of 10% to 17% and a median OS of 6.5 months; in particular, median OS was 12 months in patients responding to treatment. Regarding safety, it showed a well-tolerated profile even in the presence of impaired liver function; hematologic toxicity and PPE were the most frequently reported side effects.19, 20 Another frequently used drug was gemcitabine, which demonstrated activity against human hepatoma cells in vitro21 and as a single agent or in combination chemotherapy regimens for advanced HCC; phase 2 trials have reported a response rate of about 18%,5 with favorable toxicity (finding grade 3-4 hematological toxicity in only about 10% of patients). In light of these observations, the present study aimed at improving the efficacy of systemic chemotherapy with a favorable toxicity by combining 2 relatively active drugs in HCC with different mechanisms of cytotoxic action and potential synergistic activity, lack of cross-resistance, and nonoverlapping toxicity. In this study, we analyzed the association of pegylated liposomal doxorubicin and gemcitabine; in particular, all patients received gemcitabine, a pyrimidine nucleoside analogue, followed by the administration of pegylated liposomal doxorubicin, a type 2 antitopoisomerase.
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