Measuring medicine: How new technologies could help doctors predict patient outcomes

SAN DIEGO – As potential cancer therapies proliferate, researchers and clinicians are striving to measure their effectiveness and to more accurately predict which patients will receive the most benefit. At the American Association for Cancer Research 2008 Annual Meeting, April 12-16, 2008, researchers present data on a new role for MRI in brain cancer, how doctors can more effectively measure response to commonly used cancer drugs, and a unique method for predicting the risk of breast cancer spread.

A phase II study of the efficacy and tolerability of lapatinib in patients with advanced hepatocellular carcinomas: Abstract LB306

Results of a phase II trial suggest that lapatinib, currently approved for breast cancer treatment, shows promise for stabilizing disease in patients with liver cancer.

“Lapatinib is well-tolerated and may have some activity in hepatocellular carcinoma (HCC),” said Joseph Markowitz, M.D., Ph.D., a researcher at The Ohio State University, who works with Tanios Bekaii-Saab, MD, the principal investigator on the study. “More work is needed to understand the underlying molecular mechanisms of this cancer.”

HCC rates are rising in the United States, which correlates with the increase in hepatitis C-related liver disease, a known risk factor for HCC, Markowitz says. “There is also a link to an increased incidence of what we call ‘fatty liver’ as a result of the increasing rates of obesity and diabetes mellitus in the U.S. population.”

Lapatinib blocks the activity of the tyrosine kinase of both epidermal growth factor (EGFR) and HER2/neu, Markowitz says. “A dual inhibitor such as lapatinib should be effective in patients who express one or both receptors. Given the lack of curative or even modestly effective treatment options for patients with advanced hepatocellular carcinomas, new therapies are desperately needed,” he said.

Markowitz, Bekaii-Saab and colleagues assessed the efficacy of lapatinib as an HCC treatment in a phase II trial with 26 participants.

Patients took a 1,500 mg oral lapatinib dose daily throughout a 28-day cycle. The median number of cycles during the trial was two with some patients receiving as few as one cycle and some receiving as many as 12 cycles. The researchers performed radiological assessments every eight weeks.

In this study, where 20 percent of all patients had previous treatment before receiving lapatinib, there were no objective responses. However, 31 percent of all patients receiving lapatinib had stable disease; 8 percent had stable disease lasting longer than six months.

The most common toxicities were diarrhea (69 percent) and nausea (54 percent).Three patients had more severe toxicities including diarrhea, rash and acute renal failure. Researchers found no evidence of cardiac dysfunction. Side effects were considered tolerable.

A single-institution prospective study evaluating the functional diffusion map (fDM) as an early imaging biomarker for overall survival in high-grade glioma: Abstract LB248