B-Receptor Signaling in Cardiomyopathy
We hope to determine the importance of different genes (including B receptors) in anthracycline-induced cardiomyopathy. This has important benefits to patients exposed to anthracyclines, as this could help determine whether certain individuals have increased susceptibility to cardiac injury.
Cholangiocarcinoma of the Extrahepatic Bile Duct
Transitional Cell Carcinoma of Bladder
Bone Marrow Transplant Failure
Cancer of Brain and Nervous System
Carcinoma of the Large Intestine
Gall Bladder Cancer
Gastric (Stomach) Cancer
Gastrointestinal Stromal Tumor (GIST)
Head and Neck Cancers
Kidney (Renal Cell) Cancer
Myelodysplastic Syndromes (MDS)
Soft Tissue Sarcoma
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||B-Receptor Signaling in Cardiomyopathy|
cheek swab or blood drawn for DNA extraction
|Study Start Date:||November 2008|
|Study Completion Date:||October 2010|
|Primary Completion Date:||October 2010 (Final data collection date for primary outcome measure)|
There is a strong correlation between total doxorubicin dose and anti-tumor efficacy, however, the clinical utility of doxorubicin is severely limited by its cardiotoxicity. With improved methods of detecting subtle changes in cardiac function, e.g. alterations in left ventricular wall stress (1), the incidence of doxorubicin cardiotoxicity is now appreciated to be much higher than previously suspected, documented in 65% of long-term survivors of childhood cancer, even at doses as low as 228 mg/m2. This cardiotoxicity is dose-related, and higher doses are related to a higher incidence of clinical heart failure (2). Doxorubicin's cardiotoxicity is thought to be mediated through the generation of free radicals and through mitochondrial and membrane damage.
We wish to determine whether beta-receptor genotype affects anthracycline-induced cardiomyopathy. We will correlate beta-receptor genotype with difference in wall stress post-anthracycline exposure, and with difference in shortening fraction. We plan to recruit 300 patients over a two-year period. Inclusion criteria includes past exposure to anthracycline for cancer treatment and an echocardiogram 6 - 48 months after exposure to anthracyclines.
The mean difference in 1.) wall stress and 2.) shortening fraction between each minor allele subgroup and wild type subgroup, for both beta-1 and beta-2 will be assessed using unpaired t-test analyses . We will assess through multivariate linear regression whether there are interactions between differences in wall stress or fractional shortening and other variables such as age, gender, dose of anthracycline, type of anthracycline given, and time between anthracycline exposure and echocardiogram. Those who receive other cardiotoxic drugs (such as trastuzumab for breast cancer) will be analyzed separately.
|United States, California|
|Stanford University School of Medicine|
|Stanford, California, United States, 94305|
|Principal Investigator:||Daniel Bernstein||Stanford University|