Abstract

Purpose
Limited treatment options exist for patients with metastatic castration-resistant prostate cancer (mCRPC) after the failure of taxane-based chemotherapy and novel hormonal therapy. Here, we report the safety and efficacy of ifosfamide and mesna in patients with mCRPC after the failure of taxane-based chemotherapy and novel hormonal therapy (NCT06236789).
Materials and Methods
Patients with histologically confirmed prostate cancer who had failed taxane-based chemotherapy and novel hormonal therapy received ifosfamide 2,500 mg/m² and mesna 1,500 mg/m² on days 1–3, repeated every 21 days. Safety, objective response rate, disease control rate, reduction in serum prostate-specific antigen (PSA) concentration by >50% (PSA₅₀) or >90% (PSA₉₀), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed.
Results
A total of 47 patients with mCRPC were included in the study. The median number of lines of treatment was 5 (range: 3–7). All patients were previously administered docetaxel and novel hormonal therapies including abiraterone (51.1%) and/or enzalutamide (61.7%). Thirty-eight patients (80.9%) were administered cabazitaxel. The objective response and disease control rates were 21.3% and 80.9%, respectively. PSA₅₀ and PSA₉₀ were achieved in 31.9% and 10.6%, respectively. During a median follow-up duration of 54.3 months, rPFS and OS were 5.0 and 9.0 months, respectively. All the patients experienced treatment-related adverse events of any grades; however, no new safety signs were detected. Genomic biomarker analysis revealed that alterations in the TP53 pathway were associated with inferior rPFS and OS.
Conclusion
Ifosfamide and mesna showed appreciable efficacy and manageable safety profiles in heavily treated patients with mCRPC.

• Keywords: Metastatic castration-resistant prostate cancer, Ifosfamide, Mesna, Genomic biomarker