Doxorubicin Plus Dacarbazine Versus Doxorubicin Plus Ifosfamide in Combination With Regional Hyperthermia in Patients With Advanced Leiomyosarcoma: A Propensity Score-Matched Analysis

Abstract

Background: Dacarbazine is currently considered the better combination partner for doxorubicin compared to ifosfamide for the treatment of leiomyosarcoma (LMS). Regional hyperthermia (RHT) combined with neoadjuvant chemotherapy has been shown to improve survival in patients with locally advanced high-risk STS. We sought to evaluate the role of doxorubicin and dacarbazine (AD) versus doxorubicin and ifosfamide (AI) in combination with RHT in patients with LMS. Methods: Patients with locally advanced high-grade LMS, including limited metastases, eligible for RHT and first-line treatment with either AI + RHT or AD + RHT between 2014 and 2022 were retrospectively evaluated. Endpoints were progression-free survival (PFS) and overall survival (OS). Patients were matched using propensity scores, which were estimated with a logistic regression model accounting for tumor site, presence of metastasis, surgery, and radiotherapy. Results: A total of 105 patients were included in this study, of which 101 were included in the propensity score-matched cohort. In the matched cohort, treatment with AD + RHT was associated with a significantly improved PFS (HR 0.32, 95% CI 0.13–0.74, p = 0.0081). Multivariable analysis revealed several significant predictors of PFS, including treatment with AD + RHT (HR 0.42, 95% CI 0.19–0.92, p = 0.031). Conclusion: Treatment with AD + RHT showed improved PFS and better treatment tolerability compared to AI + RHT. Our results support the use of AD instead of AI for the treatment of patients with LMS in combination with RHT.