Real-world comparison of doxorubicin-ifosfamide versus gemcitabine-docetaxel regimens in metastatic uterine leiomyosarcoma: a multicenter retrospective study

BackgroundUterine leiomyosarcoma is a rare and aggressive malignancy with limited responsiveness to standard therapies. We conducted a real-world, multicenter study to compare the clinical efficacy and safety of two commonly used first-line chemotherapy regimens-doxorubicin-ifosfamide and gemcitabine-docetaxel-in patients with metastatic uterine leiomyosarcoma.MethodsThis retrospective cohort included 271 patients with advanced or metastatic uterine leiomyosarcoma treated between 2010 and 2023 across 30 centers in Turkey. Patients received either doxorubicin-ifosfamide (n = 142) or gemcitabine-docetaxel (n = 129) as first-line therapy. The primary endpoint was overall survival; secondary endpoints included progression-free survival, objective response rate, disease control rate, and safety. Adverse events were graded according to the Common Terminology Criteria for Adverse Events version 5.0, while survival outcomes were estimated using the Kaplan-Meier method and further analyzed with Cox proportional hazards models.ResultsMedian overall survival was 19.7 months with doxorubicin-ifosfamide and 20.2 months with gemcitabine-docetaxel (P = .26). Median progression-free survival was 5.5 months with doxorubicin-ifosfamide and 7.0 months with gemcitabine-docetaxel (P = .62). The objective response rate was numerically higher with gemcitabine-docetaxel (35% vs. 26%), although not statistically significant (P = .11). Grade 3-4 neutropenia (16% vs. 12%) and febrile neutropenia (7% vs. 6%) were more frequent with doxorubicin-ifosfamide.ConclusionsIn this largest-to-date real-world cohort of metastatic uterine leiomyosarcoma, doxorubicin-ifosfamide and gemcitabine-docetaxel demonstrated comparable survival outcomes. Gemcitabine-docetaxel, however, was associated with a more favorable hematologic safety profile. These findings support the clinical utility of both regimens while underscoring the need for prospective, biomarker-driven studies to refine treatment selection and improve personalization in this rare malignancy.