Pazopanib combined with doxorubicin and cisplatin in recurrent osteosarcoma: A retrospective cohort study

帕唑帕尼联合多柔比星和顺铂治疗复发性骨肉瘤:一项回顾性队列研究

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Abstract

Treatment options for recurrent osteosarcoma remain limited, and prognosis is poor. Pazopanib, a multi-targeted tyrosine kinase inhibitor, has shown activity in various sarcomas. This study evaluated the efficacy and safety of pazopanib combined with doxorubicin and cisplatin (Paz + AP regimen) in patients with recurrent osteosarcoma and analyzed its impact on survival. This single-center retrospective cohort study included recurrent osteosarcoma patients treated between February 2022 and February 2023. Propensity score matching was used to balance baseline characteristics. A total of 100 patients were analyzed: 50 received the Paz + AP regimen, and 50 received conventional chemotherapy (AP regimen). Treatment efficacy was assessed using response evaluation criteria in solid tumors (RECIST 1.1) criteria. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate, disease control rate, safety, and treatment compliance. Baseline characteristics were well balanced between groups (P > .05). The Paz + AP group achieved a higher disease control rate than the control group (62.0% vs 42.0%, P = .046), whereas the difference in objective response rate was not significant (26.0% vs 14.0%, P = .13). Median PFS was significantly longer in the Paz + AP group than in controls (5.1 vs 2.2 months, P = .04). Although the median OS was slightly shorter in the Paz + AP group (8.0 vs 9.6 months), its survival curve declined more slowly after 12 months, showing a significant difference (P = .03). The incidence of adverse events was comparable (92.0% vs 88.0%), though hypertension (28.0% vs 10.0%, P = .03) and hand-foot syndrome (22.0% vs 4.0%, P = .01) were more frequent with pazopanib. No differences were observed in grade ≥3 or serious adverse events. Subgroup analysis indicated greater PFS benefits among patients with lung metastasis, recurrence interval ≥6 months, Eastern Cooperative Oncology Group (ECOG 0-1), and those receiving full-dose pazopanib. The Paz + AP regimen significantly prolonged PFS and improved disease control in recurrent osteosarcoma, with manageable toxicity and good compliance. Although OS improvement was limited, the regimen showed potential clinical value, particularly for patients with favorable performance status and longer recurrence intervals. Prospective studies are warranted to confirm these findings.

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