The purpose of this study is to determine whether the drug mesna is able to block a series of chemical changes that occur in the blood of patients who receive the chemotherapy medicine doxorubicin. The researchers believe these blood chemical changes may the cause of "cloudy thinking" or "chemobrain" that are reported by some patients receiving chemotherapy.
Patients with lymphoma and breast cancer receiving chemotherapy regimens that include anthracycline drugs, such as doxorubicin, are at risk for developing cognitive and cardiac impairment. This potential cognitive impairment is refered to as "chemobrain" by some patients. We have demonstrated in mice that the drug mesna, which is used to prevent other complications of other chemotherapy drugs, prevents certain types of doxorubicin-induced damage of blood proteins. Blocking doxorubicin's damage of these blood proteins has blunted or prevented the subsequent markers of neurologic and cardiac injury in mice. This clinical trial will determine if mesna prevents doxorubicin-induced damage of blood proteins in cancer patients, and may establish if blood protein injury is the first step in anthracycline-induced cognitive and cardiac dysfunction and if using the drug mesna can blunt or prevent these changes in blood markers of injury for patients with cancer.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
32
Mesna: 360 mg/m2 in 50 mL normal saline (NS) either on cycle 2 or cycle 1, day 1. Infused over 15 minutes
Saline (used as a placebo) infused over the same time as mesna intervention
60mg/m2 given IV over 15 minutes after receiving mesna or saline. Can allow for premedications of Ondansetron 8 mg orally, dexamethasone 12 mg orally, Aprepitant 125 mg orally.
University of Kentucky Markey Cancer Center
Lexington, Kentucky, United States
TNF-alpha Levels in Patients Receiving Doxorubicin Containing Chemotherapy
Continuous Measure of TNF-alpha at the 4 time points outlined in the protocol for each group.
Time frame: prior to and 3 hours post doxorubicin and between cycles 1 and 2
Protein Carbonyl Percent Changes From Baseline in Patients Receiving Doxorubicin Containing Chemotherapy
Continuous Measure of percent changes from baseline of Protein Carbonyl at the 4 time points outlined in the protocol for each group. All measurements after naive baseline were adjusted as percent change from each individual's baseline measure.
Time frame: prior to and 3 hours post doxorubicin and between cycles 1 and 2
Plasma HNE Percent Changes From Baseline in Patients Receiving Doxorubicin Containing Chemotherapy
Continuous Measure of the percent change from baseline of Plasma HNE at the 4 time points outlined in the protocol for each group. All measurements after naive baseline were adjusted as percent change from each individual's baseline measure.
Time frame: prior to and 3 hours post doxorubicin and between cycles 1 and 2
Troponin Levels in Patients Receiving Doxorubicin Containing Chemotherapy
Continuous Measure of troponin at the 4 time points outlined in the protocol for each group.
Time frame: prior to and 3 hours post doxorubicin and between cycles 1 and 2
B-type Natriuretic Peptide (BNP) Blood Levels in Patients Receiving Doxorubicin Containing Chemotherapy
Continuous Measure of BNP at the 4 time points outlined in protocol for each of the groups. This is a 32-amino acid polypeptide secreted by heart ventricles in response to excessive stretching of cardiomyocytes.
Time frame: prior to and 3 hours post doxorubicin and between cycles 1 and 2
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600 mg/m2 IV over 30 minutes. Start 6 hours after doxorubicin started.