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Selected Articles from the August 1, 2006 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 August 1 issue of Clinical Cancer Research.
Gollob et al.
Page 4619
The silencing of gene expression through DNA methylation contributes to defects in antigen presentation and apoptosis in cancer. To determine how a hypomethylating agent would modulate the toxicity and antitumor activity of immunotherapy, Gollob et al. initiated a phase I trial of decitabine plus high-dose IL-2. Twenty-one patients were treated, and while decitabine caused grade 4 neutropenia in most patients, it did not alter the tolerability of IL-2. Objective responses were seen in 31% of melanoma patients, and decitabine altered DNA methylation and gene expression in a dose-independent manner that overlapped with the administration of IL-2. This demonstrates that decitabine can be administered safely to patients with solid tumors and shows promise for improving the response of melanoma to immunotherapy.
Simon et al.
Page 4645
CI-1033 is a pan erbB tyrosine kinase inhibitor with dose-limiting gastrointestinal toxicities when administered orally. In a study by Simon et al., CI-1033 was safely given intravenously (IV) to 53 patients with advanced non-hematologic malignancies, at levels of up to 225 mg/dose on a thrice-weekly schedule, with evidence of anti-tumor activity. At equivalent doses, bioavailability of IV CI-1033 is thrice that of the oral formulation. Treatment with IV CI-1033 is feasible and may be warranted when increased drug exposures are desired.
Hanley et al.
Page 4569
The DNA Integrity Assay (DIA) was assessed as a plasma-based screening tool for the detection of prostate cancer. Hanley et al. report that DIA detected 69.9% of prostate cancer patients and maintained a specificity of 68.2%-92%. The ROC curve demonstrated that DIA distinguishes the tumor group from the combined control groups where the area under the curve was 0.788. They have also shown that 63% of prostate cancer patients with normal, age-adjusted PSA values were identified as cancer positive using the DIA. In this way, DIA can complement PSA in screening for prostate cancer.
Ginestier et al.
Page 4533
Amplification of chromosomal region 20q13 occurs in 5-10% of breast cancers but remains poorly characterized. To isolate and analyze 20q13 -amplified tumors, Ginestier et al. used FISH for three 20q13 loci (MYBL2, STK6, ZNF217) on sections of tissue microarrays, and DNA microarrays analysis. Two amplified tumor types with opposite features were characterized. Type 1 tumors showed ZNF217 amplification without 20q13 gene overexpression and lymph node-negative status with poor prognosis. Type 2 tumors showed amplification for at least two loci with overexpression of several 20q13 genes and lymph node-positive status with good prognosis.