1,721,563 research outputs found

    Safety, efficacy, and patient acceptability of single-dose fosaprepitant regimen for the prevention of chemotherapy-induced nausea and vomiting

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    Control of chemotherapy-induced nausea and vomiting (CINV) is a crucial factor in ensuring that patients undergoing cancer chemotherapy can get the full benefit of therapy. Current antiemetic guidelines recommend that the neurokinin-1 receptor (NK-1R) antagonist aprepitant should be used as part of a combination regimen with dexamethasone and a serotonin receptor antagonist for the prevention of CINV in patients receiving highly emetogenic chemotherapy (HEC). Fosaprepitant is a water-soluble N-phosphoryl derivative of aprepitant that, when infused, is rapidly metabolized back to an active aprepitant. The existing literature in PubMed about fosaprepitant was screened and selected in order to address the emerging data from two randomized clinical trials evaluating the efficacy and safety of a single-dose fosaprepitant regimen. These phase III trials demonstrated that fosaprepitant given as a single intravenous dose of 150 mg was either noninferior to the conventional 3-day aprepitant or significantly superior to placebo for the prevention of acute and delayed CINV in patients receiving high-dose cisplatin. In both trials, fosaprepitant was well tolerated although more frequent infusion-site adverse events were observed with fosaprepitant. The new dosage regimen of fosaprepitant, therefore, would be an option for CINV control in patients receiving cisplatin-based chemotherapy. The clinical efficacy is consistent with the findings from a time-on-target, positron-emission tomography study evaluating the NK-1R occupancy in the central nervous system (CNS) over 5 days after a single-dose infusion of 150 mg fosaprepitant in healthy participants. The single-dose regimen is capable of blocking more than 90% of the NK-1Rs in the CNS for at least 48 hours after infusion, which is sufficient to control delayed CINV for 2 to 5 days after HEC. The new dosage regimen of fosaprepitant can provide a simplified treatment option that maintains high protection while ensuring adherence to scheduled antiemetic medication throughout most of the 5-day period encompassing the major risk for CINV

    Study design and clinical evidence in mRCC : can we save axitinib as a first-line therapy?

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    Tyrosine kinase inhibitors are de facto the most commonly used targeted therapies for upfront treatment of metastatic renal cell carcinoma (mRCC). After the first era in which targeted agents were compared with placebo and interferon-α, a new phase has started in recent years characterized by head-to-head trials comparing targeted agents in superiority or non-inferiority trials. Recently, the results a head-to-head phase III trial comparing axitinib to sorafenib as upfront therapy in patients affected by mRCC have been reported. We discuss several critical aspects of this study and the results of our metaanalysis on the activity of axitinib over sorafenib in a larger population with the intent to confirm the superiority of axitinib. Despite this, the definition of primary endpoint remains a central factor in determining the final results of a trial

    Adjuvant treatment of colorectal cancer in the elderly : where do we come from and where are we going?

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    Objective: Colorectal cancer is the third most commonly reported cancer in the world and about 50% of patients are diagnosed over the age of 70 years. The authors discuss age-related changes in organ function, comorbidities and frailty in the elderly, and their impact on chemotherapy toxicity. Methods: The authors review data from observational studies and subgroup analyses of randomized clinical trials on adjuvant chemotherapy in elderly colorectal cancer patients. Results: Several large population-based studies suggest that adjuvant chemotherapy is offered less frequently to elderly patients, although in recent years the prescription patterns tended to significantly increase. In fact, data from retrospective analyses of randomized trials indicate that elderly stage III colorectal cancer patients may get similar clinical advantage from adjuvant treatment with fluoropyrimidines, although major comorbidities may substantially limit life expectancy and minimize the survival benefits. The use of oxaliplatin-based regimens needs to take into account the individual risk/benefit profile due to lack of unequivocal evidence of positive literature data. Conclusions: Adjuvant chemotherapy of colorectal cancer should be investigated by prospective trials specifically designed for the elderly. Fit elderly patients should be offered standard adjuvant treatments, while modified schedule, attenuated doses or even treatment omission can be offered to more frail patients
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