The VIVA Regimen (Vinorelbine, Ifosfamide, Vincristine, and Actinomycin-D) for High-Risk Rhabdomyosarcoma: Feasibility and Outcomes From a Single-Institution Study.

INTRODUCTION

Rhabdomyosarcoma is a highly chemosensitive tumor; however, high-risk and metastatic cases require more effective systemic treatments. This study evaluates the feasibility and efficacy of the "VIVA" regimen (vinorelbine-ifosfamide-vincristine-actinomycin D), which incorporates weekly vinorelbine into the induction phase of standard therapy.

METHODS

Between 2020 and 2025, 45 patients (median age 14 years) with high-risk or metastatic rhabdomyosarcoma were treated at the Pediatric Unit of the Istituto Nazionale Tumori in Milan. The VIVA regimen added intravenous vinorelbine (25 mg/m2) on Days 8 and 15 of the standard 3-week IVA cycle. Treatment included nine induction cycles followed by 6-12 months of maintenance therapy (vinorelbine and oral cyclophosphamide), alongside multidisciplinary local control.

RESULTS

Forty patients (89%) completed the planned nine VIVA cycles; five discontinued early due to disease progression. Among 41 evaluable patients, the overall response rate after three cycles was 95%. The estimated 3-year event-free survival (EFS) and overall survival (OS) rates were 68.0% and 78.6%, respectively. Myelotoxicity was the main side effect: grade ≥ 3 neutropenia, thrombocytopenia, and anemia occurred in 70%, 7%, and 21% of cycles, respectively. Granulocyte-colony-stimulating factor (G-CSF) was administered in 51% of cycles. Overall, 30% of the cycles required either a reduction or the omission of vinorelbine administration. Notably, 68% of patients required either no modifications (24%) or modifications in fewer than 25% of doses (44%).

CONCLUSIONS

Integrating vinorelbine into the intensive induction phase proved feasible with an acceptable toxicity profile and high response rates. Further investigations are needed to define the long-term efficacy of this promising intensive regimen.