Use of Cardioprotective Dexrazoxane Is Associated with Increased Myelotoxicity in Anthracycline-Treated Soft-Tissue Sarcoma Patients

Abstract

Background: Dexrazoxane (DEX) is indicated as a cardioprotective agent for breast cancer patients receiving the anthracycline doxorubicin. Two meta-analyses in metastatic breast cancer reported an apparent increase in the severity of myelosuppression when DEX was used. So far, no data in soft-tissue sarcoma (STS) patients are available. Methods: We retrospectively analyzed hematological toxicity data from 133 consecutive STS patients who received a chemotherapy regimen containing an anthracycline and ifosfamide (AI) in the perioperative or metastatic settings between January 2006 and December 2017. Of these, 46 received off-label DEX concurrently with the AI treatment. The differences between incidence of any of the explored outcomes were assessed according to the Fisher exact test. Results: Compared with the non-DEX group, DEX treatment was associated with significantly higher rates of grade 3/4 hematological toxicities: leukopenia (56.5 vs. 28.7%; p = 0.0014), neutropenia (69.6 vs. 24.1%; p = 0.0001), febrile neutropenia (52.2 vs. 20.7%; p = 0.0004), anemia (41.3 vs. 28.7%; p = 0.1758), and thrombocytopenia (54.3 vs. 32.1%; p = 0.0159). Similarly, in the DEX group dose reductions were more frequent compared to the non-DEX group (39.1 vs. 19.5%; p = 0.0221). Conclusion: Adding DEX to AI in STS patients leads to higher rates of bone marrow suppression in all blood components, as well as to more frequent events of febrile neutropenia and dose reductions.