New research presented at the 2008 Annual Meeting of the American Association for Cancer Research (AACR), held April 12–16, brought more than 17,000 participants from 60 countries to San Diego. Among nearly 6,000 abstracts presented on basic, clinical, and translational cancer investigations, the following findings represent a few of the highlights, as announced by AACR.
DFMO Reduces Colon Cancer Risk: A combination of the targeted agent difluoromethylornithine (DFMO) at a low dose and sulindac, a nonsteroidal anti-inflammatory drug, reduces the risk of recurrent colorectal adenomas, an early sign of colon cancer, by up to 95%, with less toxicity than with chemotherapy, researchers reported (abstract LB-142).
"There is a great hope that we will be able to prevent colon cancer effectively using this method. We had not been able to do this before due to the high toxicity of available therapies. [DFMO] is a targeted agent that represents a new treatment paradigm," said Frank Meyskens, MD, of the University of California at Irvine.
For this phase III study, researchers enrolled 375 patients with a history of at least one colorectal polyp within the previous 5 years. Patients were randomized to either a combination of 500 mg of daily DFMO and 150 mg of sulindac, or placebo. After 3 years, the combination treatment reduced the risk of a recurrent adenoma from 41.1% in the placebo group to 12.3% with treatment, a 70% reduction. An analysis of toxicity found no difference between the treatment and placebo groups.
Sunitinib and Liver Cancer: Treatment with sunitinib (Sutent) slows tumor growth and reduces the risk of metastasis in patients with hepatocellular carcinoma, researchers reported (abstract LB-139). They enrolled 34 patients with advanced liver cancer in a phase II trial of sunitinib, 37.5 mg/d, on a 4-weeks-on, 2-weeks-off regimen. By 12 weeks, 1 patient had a partial response and 17 had stable disease. The median progression-free survival was 4 months, and the median overall survival was 10 months.
"Patients with this type of liver cancer have a very poor prognosis and the only currently available therapy is sorafenib [Nexavar]," said Andrew X. Zhu, MD, PHD, of Massachusetts General Hospital Cancer Center. "Giving these patients more options would have a significant impact."
Neoadjuvant Bevacizumab Plus Chemoradiation in Rectal Cancer: Adding bevacizumab (Avastin) to standard chemotherapy and radiation in patients with rectal cancer fully prevented tumor spread and "normalized" tumor blood vessels enough to enable effective therapy, researchers reported (abstract LB-304).
Researchers enrolled 24 patients with late-stage rectal cancer in this phase I/II trial. All patients completed four cycles of therapy including bevacizumab, additional standard chemotherapy, radiation, and surgery. At 4 years, local control, or the absence of cancer spread beyond the original tumor site, was observed in 100% of patients and disease-free survival in 88%.
"Although this needs to be confirmed in a randomized trial against a placebo group, these are very impressive numbers," said Rakesh Jain, phd, of Harvard Medical School.
Cediranib in Glioblastoma: The investigational drug AZD2171 (cediranib) may help shrink tumors and prolong survival of glioblastoma patients, according to a trial conducted by Boston researchers (abstract LB-247).
In a phase II study of 31 patients with recurrent glioblastoma, researchers found that daily cediranib decreased tumor volume by more than half in 56% of patients. Nearly 26% of patients were alive and their cancer had not progressed 6 months into treatment. Patients experienced a mean progression-free survival of 117 days and overall survival of 221 days. In addition, cediranib was found to alleviate brain swelling—a major cause of morbidity among these patients.
Cervical Cancer Vaccine: Phase I/ II results have shown that the live Listeria cancer vaccine, Lovaxin C, is safe for humans and may reduce tumor size in cervical cancer patients (abstract 225).
"We are using Listeria to deliver tumor-specific antigens to the immune system in a manner that results in maximal immune and tumor-clearing response," said John Rothman, PHD, of Advaxis, which is developing Lovaxin C. The trial included 15 women with progressive, recurrent, or advanced cervical cancer, divided into three groups of five; each group received two doses of Listeria at 3-week intervals.
The researchers used RECIST criteria to assess the tumors in 13 patients. At the end of the study, five patients had disease progression, seven were stable, and one showed a partial response to therapy. Three of the stable patients had tumor reductions of about 20%.