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.

Nanomicelles co-loaded with doxorubicin and salvianolic acid A for breast cancer chemotherapy

“…7,8 Unfortunately, its clinical use has been restricted due to carcinogenic potential with an increased risk for development of acute myeloid leukemia and myelodysplastic syndrome. 9,10 In recently years, oxidative stress caused by excessive production of reactive oxygen species (ROS) has been the most widely investigated and accepted mechanism of DOX induced cardiotoxicity, and natural antioxidative molecules with good e cacy and safety have attracted increasingly high attention. [11][12][13][14][15] However, drug delivery system research is still a huge challenge to realize further development and clinical application of these promising cardioprotective candidates mainly due to undesirable physico-chemical properties.…”

POSSIBLE CARDIOPROTECTIVE MECHANISM OF ACTION OF DEXRAZOXANE, AND PROBABLE HUMAN TOPOISOMERASE IIβ INHIBITORS: AN IN SILICO ANALYSIS

“…Reducing the cumulative dose of anthracycline is the main approach to preventing the cardiotoxicity, in addition, treatment with dexrazoxane (DEX), the only FDA-approved antidote, is recommended against some anthracycline-related cardiotoxicities and accidental anthracycline extravasation [5][6][7][8]. Clinical use of DEX, however, is limited due to concerns that it may increase the myelosuppressive effects of anthracyclines and ifosfamide [9] and it may also cause secondary malignancies after treatment for some pediatric cancers [10,11]. DEX (ICRF-187); is a (S)-4,4'-(1-methyl-1,2-ethanedyl) bis-2,6-piperazinedione and belongs to the bisdioxopiperazines [12].…”

Prophylactic, single-drug cardioprotection in a comparative, experimental study of doxorubicin-induced cardiomyopathy

“…Although many reviews have suggested the prophylactic use of the ironchelator dexrazoxane for cardioprotection, some human studies have revealed a higher frequency of the haematological side effects of this drug (leukopenia, neutropenia, thrombocytopenia, etc.) in patients receiving AC therapy supplemented with dexrazoxane [28][29][30]. In the past, several heart failure (HF) medications (β-blockers, inhibitors of the renin-angiotensin-aldosterone system, lipid-lowering agents) were also examined in both animal models and human trials with varying success rates [31][32][33][34][35][36][37][38][39].…”