(P 341) PROGNOSTIC RELEVANCE OF CYCLOPHOSPHAMIDE DOSE FOR HIGH-RISK RHABDOMYOSARCOMA IN ADULT PATIENTS TREATED WITH VAC THERAPY

Objective: Adult rhabdomyosarcoma (RMS) is often classified as high-risk and has a poor prognosis. Treatment strategies frequently follow pediatric protocols, such as vincristine, actinomycin D, and cyclophosphamide (VAC) regimen, despite concerns regarding toxicity in adults. Although higher doses of cyclophosphamide (CPA) may improve outcomes, the optimal dosing in adult patients remains unclear due to limited adult-specific data. In this study, we evaluated the association between the dose intensity of CPA and outcomes for high-risk RMS in adult patients.

Methods: We retrospectively reviewed patients with histologically confirmed RMS who received VAC therapy as initial chemotherapy at our institution between February 2014 and April 2024. High-risk was defined according to the Children’s Oncology Group (COG) classification, and all patients had distant metastasis. We classified the patients as pediatric (≤19 years) and adults (≥20 years). CPA dose was administered at initial dose into three groups (1.2, 1.5, or 2.2 g/m²); 2.2 g/m² was mainly used in adults, the dose was reduced after 4–7 cycles mainly due to hematologic tolerability concerns. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan–Meier method.

Results: During the study period, 40 patients with high-risk RMS received VAC therapy at our institution. Three patients were excluded (1 discontinued follow-up during VAC, 2 received VAC on an irregular schedule). Among the 37 patients analyzed, 13 were pediatric (median age, 14; range, 5-19) and 24 were adults (median age, 27; range, 20-60). Alveolar histology was noted in 25 patients (67.6%), all of whom were positive for FOXO1 fusion. The median PFS was 13 months in pediatric patients and 7 months in adults (p = 0.0023). The median OS was 37 months in pediatric patients and 12 months in adults (p = 0.0022). Among adult, 8 patients received CPA at a dose of 1.2 g/m², 1 received 1.5 g/m², and 15 received 2.2 g/m². No statistically significant differences were observed in PFS (p = 0.77) or OS (p = 0.54) between patients who received 1.2 g/m² and those who received 2.2 g/m².

Conclusion: In this retrospective analysis, a high starting dose of cyclophosphamide did not result in a statistically significant survival difference compared to a low-dose regimen in adult patients with high-risk RMS.