GPX-150 treatment in metastatic and unresectable soft tissue sarcoma resulted in progression-free survival rates of 38% at 6 months and 12% at 12 months, with no evidence of chronic cardiotoxicity.
Does GPX-150 provide efficacy without irreversible, cumulative dose-dependent chronic cardiotoxicity in patients with metastatic and unresectable soft tissue sarcoma?
GPX-150 demonstrated efficacy in soft tissue sarcoma without causing irreversible, cumulative dose-dependent chronic cardiotoxicity, potentially offering a safer alternative to doxorubicin.
BACKGROUND: 13-Deoxy, 5-iminodoxorubicin (GPX-150) is a doxorubicin (DOX) analog synthesized to reduce the formation of reactive oxygen species and the cardiotoxic metabolite, doxorubiciniol, the two pathways that are linked to the irreversible, cumulative dose-dependent cardiotoxicity of DOX. In a preclinical chronic models and a phase I clinical study of GPX-150, no irreversible, cumulative dose-dependent cardiotoxicity was demonstrated. Recent studies suggest that DOX cardiotoxicity may be mediated, at least in part, by the poisoning of topoisomerase IIβ. PATIENTS AND METHODS: An open-label, single-arm phase II clinical study in metastatic and unresectable soft tissue sarcoma (STS) patients was initiated to further evaluate the efficacy and safety of GPX-150, including cardiac function, specifically left ventricular ejection fraction (LVEF). RESULTS: every 3 weeks for up to 16 doses with prophylactic G-CSF until progression, death, or patient withdrawal from the study. GPX-150 exhibited efficacy assessed as progression-free survival (PFS) rates of 38% and 12% at 6 and 12 months and an overall survival rate of 74% and 45% at 6 and 12 months. GPX-150-treated patients did not develop any evidence of irreversible, cumulative dose-dependent chronic cardiotoxicity. Toxicities included grade 3 anemia, neutropenia, and one grade 4 leukopenia. Correlative analysis demonstrated that GPX-150 was more selective than DOX for the inhibition of topoisomerase IIα over IIβ in vitro. CONCLUSION: .
Tine et al. (Tue,) conducted a other in Metastatic and unresectable soft tissue sarcoma. 13-Deoxy, 5-iminodoxorubicin (GPX-150) was evaluated on Progression-free survival (PFS) at 6 months. GPX-150 treatment in metastatic and unresectable soft tissue sarcoma resulted in progression-free survival rates of 38% at 6 months and 12% at 12 months, with no evidence of chronic cardiotoxicity.