April 15 Clinical Cancer Research Highlights

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Selected Articles from the April 15, 2007 Issue

The articles referenced in this Highlights section will be available online in HTML and PDF formats to all interested users at no charge until the next issue of Clinical Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the April 15 issue of Clinical Cancer Research.

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Serum Changes Detect Liver Cancer Early

Zhang et al.
Page 2378

Since most hepatocellular carcinomas (HCC) are diagnosed at an advanced and usually fatal stage, the development of screening methods for early detection is critical. Zhang et al. investigated aberrant promoter hypermethylation in serum DNA from both HCC patients who provided repeated blood samples before diagnosis and from controls. Aberrant methylation of p16, p15, and RASSF1A was found in a high frequency of cases one to nine years before clinical HCC diagnosis but rarely in controls. These results suggest that epigenetic changes detectable in serum may be valuable for early detection of HCC in high-risk populations. 

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LAK Cell Infusion Improves ADCC

Berdeja et al.
Page 2392

Antibody-dependent cellular cytotoxicity (ADCC) is an important mechanism of action of rituximab. Berdeja et al. showed that exposure to rituximab leads to a rapid decline in ADCC. To determine whether this drop in ADCC could be prevented, lymphokine-activated killer (LAK) cells were infused in the setting of IL-2 and rituximab in patients with B-cell lymphoma who were considered refractory to rituximab. The infusion of LAK cells not only prevented but also improved ADCC. This study is important in reasserting the importance of ADCC as a mechanism of action of rituximab in vivo and has implications for novel immunomodulatory combinations to exploit and improve monoclonal antibody therapy.

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Aerosolized Liposomal Cisplatin Well Tolerated   

Wittgen et al.
Page 2414

The safety and pharmacokinetics of aerosolized Sustained Release Lipid Inhalation Targeting (SLIT) Cisplatin in patients with carcinoma of the lung was investigated in a Phase I study by Wittgen et al. No dose-limiting toxicity was observed at the maximum delivered dose of 60.0 mg m^–2 given in 20 inhalations divided over three days. Safety data showed no hematological toxicity, nephrotoxicity, ototoxicity, or neurotoxicity. These results indicate that high doses of aerosolized SLIT Cisplatin can be inhaled safely. The therapeutic effect of the formulation should be established in a phase II study. The investigators concluded that the use of aerosolized liposomal cisplatin was found to be feasible and safe.

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Profiling Melanoma Patients with Serum Cytokines

Yurkovetsky et al.
Page 2422

Development of reliable serum assays may contribute to the development of methods for earlier detection of melanoma and the selection of patients who may be most susceptible to currently available interventions. Yurkovetsky et al. presented data that showed significant changes in the concentrations of multiple potential serum biomarkers of melanoma patients compared with healthy controls. The differences observed may allow the identification of a diagnostic profile of prognostic as well as predictive utility. Multiplexed cytokine profiling may potentially have utility in the monitoring of adjuvant therapy of melanoma patients for efficacy and/or for the decision whether alternative therapies would be reasonable to consider.

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