Other highlights in the October 19 JNCI

A new study has found that a treatment regimen that combines the monoclonal antibody C225 (cetuximab, Erbitux) and a method called photodynamic therapy (PDT) is synergistic and well-tolerated in a mouse model of ovarian cancer.

Because the prognosis for women diagnosed with ovarian cancer is poor--less than a third will survive 5 or more years--new treatment strategies are needed. Combination therapies directed against nonoverlapping molecular targets may be the most likely to succeed. Tayyaba Hasan, Ph.D., of Massachusetts General Hospital in Boston, and colleagues tested C225--which inhibits the epidermal growth factor receptor--and PDT--which involves laser-based activation of a light sensitive chemical--separately and in combination in a mouse model of ovarian cancer.

They found that mice treated with both C225 and PDT had a substantial reduction in mean tumor burden to 9.8% of that of no-treatment control mice, whereas mice treated with C225 only or PDT only had mean tumor burdens of 66.6% and 38.2%, respectively. Mice treated with both C225 and PDT also had a nearly three-fold increase in median survival compared with the control mice. When compared with PDT only or C225 only, C225 plus PDT produced synergistic reductions in mean tumor burden and improvements in survival.

In an editorial, Eli Glatstein, M.D., of the University of Pennsylvania in Philadelphia, and colleagues discuss the theoretical advantages of using C225 and PDT to exploit different aspects of ovarian carcinoma tumor biology.

Contacts:

• Article: Tayyaba Hasan, Massachusetts General Hospital, 617-726-6996, Thasan@partners.org
• Editorial: Pat Johnston, University of Pennsylvania, 215-662-3383, Johnston@xrt.upenn.edu

Combination Chemotherapy Not Clearly Better Than Single Agent for Treatment of Liver Cancer

In a phase III clinical trial, patients with hepatocellular (liver) carcinoma (HCC) treated with the combination of cisplatin, interferon, doxorubicin, and fluorouracil (PIAF) had a similar response and survival rate but higher toxicity than patients treated with doxorubicin alone.

HCC accounts for about 5% of cancer cases worldwide and 10% of cases in some areas of Asia. The disease is highly aggressive, and the median survival for the 80% of patients who cannot be treated with curative surgery is only 4 months. Single-agent doxorubicin has been used to treat HCC patients, but the response rate is low and there is little evidence that it improves survival.

Benny Zee, Ph.D., of the Chinese University of Hong Kong, and colleagues conducted a phase III trial in which 188 HCC patients who could not receive surgery were randomly assigned to be treated with either doxorubicin alone or PIAF. Patients who received PIAF had a higher overall response rate (20.9% versus 10.5% in patients treated with doxorubicin alone) and better survival (8.67 months versus 6.83 months), but these results were not statistically significant. In addition, patients treated with PIAF experienced more treatment-related toxicity than those who received only doxorubicin.

Contact: Benny Zee, Chinese University of Hong Kong, (852)2632-1032, benny@clo.cuhk.edu.hk

Review Examines Potential Use of Compounds in Epigenetic Cancer Therapies

In a review, Frank Lyko, Ph.D., of Deutsches Krebsforschungszentrum in Heidelberg, Germany, and Robert Brown, Ph.D., of Glasgow University in Scotland, examine the literature on DNA methyltransferase inhibitors--compounds that reverse epigenetic changes linked to cancer development--and discuss their effectiveness as antitumor agents in phase I-III clinical trials. The authors point out areas for future research and emphasize the need to develop assays for genome-wide and tumor-specific DNA methylation to maximize the therapeutic efficacy of these compounds.

Contact: Julia Rautenstrauch, Deutsches Krebsforschungszentrum, +49 6221 42 2854, J.Rautenstrauch@dkfz-heidelberg.de

Study Examines Mechanism of Tumor Cell Resistance to Angiogenesis Inhibitor

The synthetic tripeptide GSAO can inhibit angiogenesis and stop the proliferation of and cause apoptosis in dividing cells. However, normal endothelial cells are more sensitive to GSAO than tumor cells. In a new study, Philip J. Hogg, Ph.D., of the University of New South Wales in Sydney, Australia, and colleagues screened yeast deletion strains to identify yeast genes that are necessary for GSAO resistance. They then used knowledge of the function of these yeast genes to investigate the mechanism of tumor cell resistance to GSAO.

Contact: Dan Gaffney, University of New South Wales, +61 411 156 015, dgaffney@science.unsw.edu.au

Also in the October 19 JNCI:

• Study Examines Safety of Radical Prostatectomy for Older Men: http://www.eurekalert.org/emb_releases/2005-10/jotn-ses101305.php
• Study Estimates Melanoma Risk in Gene Mutation Carriers: http://www.eurekalert.org/emb_releases/2005-10/jotn-sem101305.php

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at http://jncicancerspectrum.oxfordjournals.org/.