Efficacy and safety of continuous intra-arterial cisplatin and recombinant human endostatin combined with systemic chemotherapy in osteosarcoma: A phase II study.

11523 Background: Previous studies have demonstrated that preoperative intra-arterial cisplatin infusion elicits a favorable histologic response—a key prognostic factor for survival in osteosarcoma. Recombinant human endostatin (rh-endostatin; Endostar), an anti-angiogenic agent, has been shown to significantly improve survival when administered intravenously in combination with chemotherapy for osteosarcoma. Herein, we report preliminary results on the efficacy and safety of continuous intra-arterial cisplatin and rh-endostatin combined with systemic chemotherapy in osteosarcoma (NCT06562673). Methods: This open-label, single-arm, single-center, phase II clinical trial enrolled patients with histologically confirmed primary localized extremity conventional osteosarcoma. Patients received 2 cycles of high-dose methotrexate and anthracyclines intravenously. Intra-arterial infusion was performed concurrently with anthracyclines. Rh-endostatin was administered intra-arterially (150 mg over 6 hours); then, cisplatin was administered intra-arterially (100-120 mg/m² over 6 hours). Efficacy and safety were evaluated after surgery. Results: Ten patients were enrolled from December 2024, to April 2025, including 7 males and 3 females with a mean age of 17.8 years (range, 12-42 years). Tumor locations included the femur (n=6), tibia (n=3), and humerus (n=1). Preoperative arterial infusions were administered 3 times (n=1), 2 times (n=8), and 1 time (n=1). All patients underwent limb-sparing surgery. The tumor necrosis rate was >90% in 5 cases (50%) and ≤90% in 5 cases (50%). Adverse events included grade 3 vomiting and nausea (n=1), grade 1 renal impairment (n=2), fever (n=1), and skin induration (n=1). Due to grade 3 gastrointestinal toxicity observed in the first enrolled female patient, the cisplatin dose was uniformly reduced to 100 mg/m² for all subsequent patients in the trial. Conclusions: Intra-arterial administration of high-dose rh-endostatin and cisplatin combined with systemic chemotherapy in osteosarcoma appears safe and achieves a good histologic response rate of 50%, compared with a historical rate of 30% with intravenous chemotherapy alone. Clinical trial information: NCT06562673 .