Effects Of Carvedilol And Zinc Sulfate On Doxorubicin Induced Cardiotoxicity In Females With Breast Cancer

Doxorubicin based regimen ( DBR ) is the most common treatment of breast cancer that is highly complicated by cardiotoxicity. The risk of cardiotoxicity is the most serious drawback to the clinical usefulness of doxorubicin . Nevertheless, doxorubicin remains among the most widely used anticancer drugs. Aim : To assess the value of carvedilol in different doses and zinc sulfate on some clinical and biochemical parameters of cardiotoxicity. Patients and Methods : A total of 32 females with breast cancer were enrolled in this study. The patients were randomized into 4 groups , (8 patients / group). Group I included patients were treated with DBR for 6 cycles with 21 day interval . Group II included patients were received the same regimen plus carvedilol 3.125 mg , orally , twice daily for 5 days , for 6 cycles. Group III consisted of patients were treated with the same regimen plus carvedilol 6.25 mg, orally, twice daily for 5 days , for 6 cycles. Group IV comprised patients were received the same regimen plus zinc sulfate 220 mg , orally , twice daily for 5 days , for 6 cycles. Each patient underwent electrocardiography (ECG) , chest X-Ray (CXR), Echocardiography to measure ejection fraction and fraction shortening at zero time and 3 days after 2nd , 4th and 6th cycles. The blood samples were taken at zero time and after 12 hr and 3 days after 2nd , 4th and 6th cycles to measure the following parameters: Creatine kinase ( CK- MB ), troponin I ( TRP I ), C-reactive protein ( CRP) , Myoglobin and malondialdhyde (MDA). Results: The following results were obtained: 1- Treatment with DBR , DBR + carvedilol 3.125mg , DBR + carvedilol 6.25 mg or DBR + zinc Sulfate 220 mg caused no significant ECG or CXR findings after 2nd , 4th and 6th cycles ( P > 0.05 ).
2- Treatment with DBR in group I caused highly significant decrease in echocardiographic ejection fraction and fraction shortening and highly significant increase in serum levels of CK-MB , TRP I , C-RP , myoglobin and MDA after 2nd , 4th and 6th cycles in comparison to baseline readings ( P < 0.01 ). 3- Regarding group II , there was highly significant increment in echocardiographic ejection fraction and fraction shortening and high significant decrement in serum level of CK-MB , TRP I , C-RP, myoglobin and MDA in comparison to that of DBR group ( P< 0.01 ). 4- In group III , there was highly significant increment in echocardiographic ejection fraction and fraction shortening and highly significant decrement in serum level of CK-MB , TRP I , C-RP, myoglobin and MDA in comparison to that in DBR group ( P< 0.01 ). 5- Regarding group IV , there was significant increment in echocardiographic ejection fraction and fraction shortening and highly significant decrement in serum level of CK-MB , TRP I , C-RP and Myoglobin ( P< 0.01 ) and significant decrease in serum MDA level in comparison to that of DBR group ( P< 0.05 ). Conclusion: 1- Each of carvedilol and zinc sulfate exert a protective effect on doxorubicin induced cardiotoxicity. 2- there was no significant difference between 3.125 mg and 6.25 mg of carvedilol in their effects on clinical and biochemical parameters. 3- Carvedilol was better than zinc sulfate regarding its improvement of clinical and biochemical markers of cardiotoxicity.