Real-World Activity and Safety of Metronomic Cyclophosphamide in Advanced Soft-Tissue Sarcoma: The Multicenter MeRCY Study

Background/Objectives: Metronomic cyclophosphamide (MCP) is sometimes used for advanced soft-tissue sarcoma (STS) when standard therapies are unsuitable. We assessed its activity and safety in routine practice. Methods: This French three-center retrospective study included 60 adults with unresectable or metastatic STS who started MCP in 2008–2021. Patients received oral cyclophosphamide 50 mg twice daily on days 1–7 of 14-day cycles; 12 (20%) also received prednisolone during treatment weeks. The primary endpoint was progression-free survival (PFS). Results: Median age was 70 years; 55% had ECOG performance status 2–3. Median PFS and overall survival (OS) were 2.6 months (95% CI, 1.8–3.6) and 6.4 months (95% CI, 4.2–9.3), respectively. The objective response rate was 5.0% (3/60; exact 95% CI, 1.0–13.9%) and the disease control rate was 21.7% (13/60; exact 95% CI, 12.1–34.2%); ten patients (16.7%) were not radiologically evaluable. In 21 patients aged >65 years treated in the first- or second-line setting, median PFS and OS were 3.2 and 7.7 months. Treatment-related adverse events were documented in 16 patients (26.7%), with no grade ≥3 events recorded. Conclusions: Intermittent low-dose MCP showed limited antitumor activity but favorable clinician-documented short-term tolerability in this multicenter cohort. Alongside prospective evidence, the results do not support routine use in unselected patients. MCP may retain an individualized palliative role when established systemic therapy is unsuitable.