A Phase II Study Of The Efficacy And Tolerability Of Lapatinib In Patients With Advanced Hepatocellular Carcinomas
"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
Researchers have found that functional diffusion mapping (fDM), which assesses early changes in tumors by diffusion MRI, can provide an earlier assessment of response for patients with glioma, a notoriously hard-to-treat cancer of the central nervous system.
"Diffusion MRI does not necessarily make a better picture of the tumor, but it may be able to assess the response of the tumor to therapy much faster than traditional MRI images," said Brian D. Ross, Ph.D., co-director for the Center for Molecular Imaging at the University of Michigan. "In addition, by combining diffusion MRI and conventional MRI, one can get a better measurement of results than could be achieved with either test alone."
Diffusion MRI is a type of magnetic resonance imaging scan that can be performed on any MRI system and which allows for the measurement of the movement of water within body tissue. It is commonly used to evaluate brain injury in stroke patients, and is gaining clinical popularity as a method for distinguishing different types of tissues or tumors.
In this study, researchers assessed brain tumor response by diffusion MRI in 60 patients with high grade glioma who were undergoing radiation therapy. The patients were assessed at one, three and 10 weeks after the start of radiation treatment. Researchers found measurable changes in diffusion MRI as assessed by fDM as early as the first week of treatment. Assessment at week three of therapy was a strong predictor of survival at one year. The strongest predictor was a combination of diffusion MRI and conventional MRI at week 10.
Ross says diffusion MRI is a better predictor of outcome at early stages of disease because it measures changes in cellular density. Researchers believe that a tumor responding to treatment will show decreased cell density, and, as a result, surrounding water will move more freely. Diffusion MRI enables physicians to see this water movement almost immediately instead of waiting the eight to 10 weeks traditionally needed to see if a particular treatment, such as radiation therapy, has shrunk a tumor, or if the tumor has grown.
This is a more accurate measure of tumor response than simply measuring the size of the tumor. "Tumors may appear to get larger or have more contrast enhancement as a response to therapy even if the tumor is not actually growing," said Ross. "Diffusion MRI may help differentiate which patients are doing well even if the tumor grows."
A phase II study of the efficacy and tolerability of lapatinib in patients with advanced hepatocellular carcinomas
Abstract LB306
This was presented at the 2008 Annual Meeting of the American Association for Cancer Research.
The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 27,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication and its sixth major journal, Cancer Prevention Research, is the only journal worldwide dedicated exclusively to cancer prevention, from preclinical research to clinical trials. The AACR also publishes CR, a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.
American Association for Cancer Research
Un studiu de faza II studiu cu privire la eficacitatea ºi tolerabilitãþii Lapatinib la pacienþii cu carcinoame Hepatocellular avansatã - A Phase II Study Of The Efficacy And Tolerability Of Lapatinib In Patients With Advanced Hepatocellular Carcinomas - articole medicale engleza - startsanatate