B-Receptor Signaling in Cardiomyopathy
|Carcinomas Amyloidosis Anal Cancer Anemia Cholangiocarcinoma of the Extrahepatic Bile Duct Transitional Cell Carcinoma of Bladder Bone Marrow Transplant Failure Bone Cancer Cancer of Brain and Nervous System Breast Cancer Carcinoma of the Large Intestine Endocrine Cancer Esophageal Cancer Eye Cancer Gall Bladder Cancer Gastric (Stomach) Cancer Gastrooesophageal Cancer Gastrointestinal Stromal Tumor (GIST) Gynecologic Cancers Head and Neck Cancers Hepatobiliary Neoplasm Kidney (Renal Cell) Cancer Leukemia Lung Cancer Hodgkin Disease Lymphoma, Non-Hodgkin Mesothelioma Multiple Myeloma Myelodysplastic Syndromes (MDS) Neuroendocrine Tumors Myeloproliferative Disorders Pancreatic Cancer Prostate Cancer Skin Cancer Soft Tissue Sarcoma Testicular Cancer Thymus Cancer Thyroid Cancer|
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||B-Receptor Signaling in Cardiomyopathy|
- Development of cardiomyopathy [ Time Frame: Within 5 years after receiving anthracyclines. ]Decrease in fractional shortening below normal (<28%)
Biospecimen Retention: Samples Without DNA
|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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01135849
|United States, California|
|Stanford University School of Medicine|
|Stanford, California, United States, 94305|
|Principal Investigator:||Daniel Bernstein||Stanford University|