A single 7.5-mg intravenous dose of rasburicase appeared to have effects similar to those of a single 0.15-mg/kg intravenous dose for the treatment or prevention of hyperuricemia associated with tumor lysis syndrome. This low fixed dose also has the potential to reduce costs.

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PurposeTo review the treatment of metastatic renal cell carcinoma (RCC), including the use of new targeted therapies. MethodsA search of MEDLINE (1966 to August 2008 and American Society of Clinical Oncology Meeting abstracts (2005 to May 2008) was preformed using the search terms bevacizumab, everolimus, interferonalfa (IFN-α), interleukin-2 (IL-2), sorafenib, sunitinib, temsirolimus, and RCC. Articles most pertinent to the treatment of metastatic RCC are reviewed. ResultsThe treatment of metastatic RCC has undergone a paradigm shift over the past 5 years from biologic response modifiers to new targeted therapies. Historically, response rates for the biological response modifiers, aldesleukin (IL-2), and IFN-α were approximately 15%. Recently, three targeted agents, sorafenib, sunitinib, and temsirolimus have been approved for the treatment of RCC. Additionally, bevacizumab has been investigated and shown to increase progression free survival in RCC. IL-2 remains the only agent to induce complete, durable remissions; however, many patients are not eligible for this therapy. Newer agents (sorafenib, sunitinib, and temsirolimus) have shown to be superior to IFN-α or placebo and bevacizumab combined with IFN-α has shown activity when compared to IFN-α alone. Unlike IL-2, the greatest benefit obtained with targeted therapies is in achieving stable disease (SD). Despite their benefit, targeted therapies have never been compared with each other in clinical trials and choosing the most appropriate agent remains challenging. To date, the optimal sequence or combination of treatments has not been defined; however, everolimus has recently demonstrated activity in patients progressing on targeted therapy. ConclusionsIL-2 remains the most active regimen in inducing complete responses; however, its use is accompanied by substantial morbidity and is limited to those with a good performance status. Targeted therapies are also efficacious in the treatment of RCC, with the major benefit being induction of SD. Future research will better define the sequencing of therapies, as well as, explore the activity of novel combination regimens.

AIMSThe aim was to assess potential interaction between methotrexate (MTX) and proton pump inhibitors (PPIs) in patients receiving high-dose MTX. METHODSRecords of 56 adults receiving 201 cycles of MTX were reviewed to determine effects of PPI administration on MTX elimination. Repeated-measures logistic regressions and Cox regressions were performed to evaluate the possible drug interaction. RESULTSDespite a significant difference between those receiving a PPI and not receiving a PPI in median MTX levels at 24 (8.0 vs. 3.9 μmol l −1 , respectively, P = 0.013) and 72 h after MTX administration (0.08 vs. 0.05 μmol l −1 , respectively, P = 0.037), there was no difference between those receiving a PPI and not receiving a PPI in the proportion of patients experiencing delayed elimination at 24 (19.2% vs. 20.2%, respectively, P = 1.000) and 72 h (36.2% vs. 33.7%, respectively, P = 0.765). When data were analysed using Cox regression, controlling for multiple cycles of MTX per patient, PPI use was not a significant predictor of time to MTX < 0.1 μmol l −1. When the clustering effect of multiple cycles of MTX per patient was controlled for, co-administration of PPIs was not a significant predictor of MTX level (P = 0.969). A comparison of patients with delayed elimination at any time point and those without delayed elimination indicated that PPI use was not a significant predictor of delayed elimination (P = 0.607). CONCLUSIONSThis study does not support previous findings of a significant interaction between PPIs and MTX. Based on these results, the clinical significance of any potential interaction is likely to be small.