Prevention of CHOP-induced Chronic Cardiotoxicity

Doxorubicin has been one of the most important key drugs in treatment for malignancies. However, its use is limited by dose-dependent cumulative cardiotoxicity. This multi-centers trial was designed to investigate the preventive effect of Valsartan, the angiotensin II type 1 receptor blocker (ARB) on chronic cardiotoxicity due to doxorubicin based chemotherapy. Patients with untreated non-Hodgkin's lymphoma who are scheduled to receive at least 6 courses of the standard CHOP (-R) will be randomized by the minimization methods to the treatment group with Valsartan (80mg once daily by oral during entire 6 courses of CHOP) or control group. Cardiac function will be evaluated in detail before and after 3 and 6 courses of CHOP (-R).

Inclusion criteria

• Clinical diagnosis of non-Hodgkin's lymphoma (NHL)
• Untreated lymphoma
• Performance status from 0 to 1,
• Total serum bilirubin < 2.0 mg/dl
• Serum creatinine level < 2.0 mg/dl
• Ejection fraction of the left ventricle >50 %
• Systolic blood pressure at rest being 90 mmHg or more

Exclusion criteria

• Severe complication including chronic or acute heart failure, angina, old myocardial infarction, liver cirrhosis, and interstitial pneumonia
• Pregnancy, nursing mothers or women of child-bearing potential
• Hypertension under medication
• Diabetes mellitus under medication
• Hyperthyroidism, nephrotic syndrome, Cushing's syndrome
• Atrial arrythmias
• Severe psychopathy
• Cerebrovascular accidents within the past 3 months
• Positive serum HBs antigen or HCV antibody
• A history of renal failure
• A contraindication to A-II antagonists or noncompliance
• Treatment with any of the following drugs within the past 3 months : A-II antagonists, ACE inhibitors, vitamin E, probucol, calcium antagonists, beta-blockers, and steroid pulse therapy.