(P 208) LOW INCIDENCE OF CANCER THERAPY-RELATED CARDIAC DYSFUNCTION IN ADULT SARCOMA PATIENTS RECEIVING DOXORUBICIN AND UPFRONT DEXRAZOXANE

Objective: Anthracycline-based chemotherapy remains standard first-line treatment for many patients with bone or soft tissue sarcoma. However, clinical utility of anthracyclines may be limited by cancer therapy-related cardiac dysfunction (CTRCD), including cardiomyopathy with left ventricular (LV) dysfunction. The estimated incidence of CTRCD is 3-5% at a 400 mg/m2 cumulative doxorubicin dose. This increases to 7-26% after 550 mg/m2 and up to 48% after 700 mg/m2. Due to therapeutic benefit, sarcoma patients frequently receive beyond the recommended cumulative dose of 400-550 mg/m2. Current strategies to decrease cardiotoxicity include administering doxorubicin as a continuous infusion or in combination with dexrazoxane, a cardioprotective agent. Prophylactic dexrazoxane is currently approved by the United States Food and Drug Administration (FDA) for use with doxorubicin doses above 300 mg/m2 in breast cancer, while upfront use remains controversial due to theoretical concerns for reduced efficacy, added myelosuppression, and secondary malignancies. To date, strategies to decrease anthracycline induced cardiotoxicity vary between sarcoma centers. The objectives of this study were to evaluate the rate of CTRCD and treatment outcomes with the combination of doxorubicin and dexrazoxane upfront for the treatment of adult sarcoma patients at our institution.

Methods: This retrospective cohort study was approved by the University of Miami Institutional Review Board (IRB) and included 87 patients who received at least 400 mg/m2 of doxorubicin with dexrazoxane for the treatment of sarcoma from January 2015 to December 2021. Of the 87 patients, 57 received 400-550 mg/m2, 21 received 551-700 mg/m2, and 9 received above 700 mg/m2. The primary outcome was the incidence of CTRCD, defined as LV ejection fraction (LVEF) decrease of at least 10% from baseline resulting in LVEF less than 50%. Secondary aims included progression free survival (PFS), hospitalization for cardiac-related events, cardiac-related death, and secondary malignancy.

Results: CTRCD developed in 4/87 patients (4.6%). All four of the patients with CTRCD received cumulative doxorubicin doses between 400-550 mg/m2. Interestingly, 0/30 patients who received doses greater than 550 mg/m2 developed CTRCD. Two patients (2%) developed symptomatic CTRCD and both patients had metastatic disease. The median cumulative doxorubicin dose was 467 mg/m2 (range 430-1001 mg/m2) and median doxorubicin dose per cycle was 75 mg/m2 (range 60-96).

Conclusion: These results suggest upfront concomitant use of dexrazoxane with doxorubicin may be associated with lower rates of CTRCD. From our data there is no evidence to support a maximum cumulative doxorubicin dose recommendation when given in combination with upfront dexrazoxane. Limitations include retrospective nature, limited sample size, and lack of control arm. Further analysis, including cost-analysis, is warranted to support this practice.