Safety and Efficacy of Vinorelbine and Continuous Low‐Dose Cyclophosphamide Chemotherapy in Japanese Pediatric Patients With Relapsed or Refractory Rhabdomyosarcoma

BACKGROUND: Relapsed or refractory rhabdomyosarcoma (RMS) has a poor prognosis, and optimal treatment remains an unmet need. Vinorelbine (VNR) and low-dose metronomic cyclophosphamide (CPM) have shown clinical efficacy and are used as maintenance therapy in localized and metastatic disease; however, dose reductions are frequently required due to myelosuppression. This study evaluated the safety, efficacy, and optimal dosing of VNR and CPM in pediatric patients with relapsed or refractory RMS. METHODS: Pediatric patients treated with VNR and CPM at our institution between March 2014 and May 2024 were retrospectively reviewed. Dosing was based on the RMS 2005 protocol, with dose reductions implemented before or during treatment to minimize treatment interruptions. RESULTS: Eighteen patients received 139 cycles of therapy (median age at initiation, 15.6 years; range, 7-21 years), including 13 relapsed and 5 refractory cases. The median number of cycles administered was 5.5 (range, 1-26), with a median interval of 28 days. The median adjusted dose ratios over three cycles were 55% for VNR and 53.5% for CPM. Disease control lasting longer than 10 months was achieved in six patients (33%). Neutropenia occurred in 89% of patients, whereas anemia and thrombocytopenia requiring transfusion occurred in 28% and 22%, respectively. No grade 4 non-hematologic toxicities or treatment-related deaths were observed after dose adjustment. CONCLUSIONS: VNR and continuous low-dose CPM chemotherapy were safe and feasible with dose adjustments. In heavily pretreated patients, initiating therapy at approximately 80% of the standard dose may be appropriate.