Cancer Research and Treatment

Original Articles

Efficacy and Safety of Ifosfamide and Mesna in Metastatic Castration-Resistant Prostate Cancer after Taxane-Based Chemotherapy and Novel Hormonal Therapy Failure: Chang Gon Kim, Yeo Gyeong Ko, Jongjin Yoon, Chung Lee, Seung Hoon Beom, Young-Deuk Choi, Woong Kyu Han, Won Sik Ham, Hyunho Han, Jongsoo Lee, Ji Eun Heo, Daeseong Kim, Eun Sil Baek, Sangwoo Kim, Minsun Jung, Sang Joon Shin; Received February 10, 2025 Accepted June 8, 2025 Published online June 9, 2025; DOI: https://doi.org/10.4143/crt.2025.155 [Accepted]

Abstract PDF: 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.

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General

Clinicopathological Characteristics of NRG1 Fusion–Positive Solid Tumors in Korean Patients: Yoon Jin Cha, Chung Lee, Bio Joo, Kyung A Kim, Choong-kun Lee, Hyo Sup Shim; Cancer Res Treat. 2023;55(4):1087-1095. Published online June 15, 2023; DOI: https://doi.org/10.4143/crt.2023.682

Abstract PDF PubReader ePub

Purpose
Neuregulin 1 (NRG1) gene fusion is a potentially actionable oncogenic driver. The oncoprotein binds to ERBB3-ERBB2 heterodimers and activates downstream signaling, supporting a therapeutic approach for inhibiting ERBB3/ERBB2. However, the frequency and clinicopathological features of solid tumors harboring NRG1 fusions in Korean patients remain largely unknown.
Materials and Methods
We reviewed archival data from next-generation sequencing panel tests conducted at a single institution, specifically selecting patients with in-frame fusions that preserved the functional domain. The clinicopathological characteristics of patients harboring NRG1 fusions were retrospectively reviewed.
Results
Out of 8,148 patients, NRG1 fusions were identified in 22 patients (0.27%). The average age of the patients was 59 years (range, 32 to 78 years), and the male-to-female ratio was 1:1.2. The lung was the most frequently observed primary site (n=13), followed by the pancreaticobiliary tract (n=3), gastrointestinal tract (n=2, stomach and rectum each), ovary (n=2), breast (n=1), and soft tissue (n=1). Histologically, all tumors demonstrated adenocarcinoma histology, with the exception of one case of sarcoma. CD74 (n=8) and SLC3A2 (n=4) were the most frequently identified fusion partners. Dominant features included the presence of fewer than three co-occurring genetic alterations, a low tumor mutation burden, and low programmed death-ligand 1 expression. Various clinical responses were observed in patients with NRG1 fusions.
Conclusion
Despite the rarity of NRG1 fusions in Korean patients with solid tumors, identification through next-generation sequencing enables the possibility of new targeted therapies.

Citations

Citations to this article as recorded by

Continuous multimodal data supply chain and expandable clinical decision support for oncology
Jee Suk Chang, Hyunwook Kim, Eun Sil Baek, Jeong Eun Choi, Joon Seok Lim, Jin Sung Kim, Sang Joon Shin
npj Digital Medicine.2025;[Epub] CrossRef
Expert Consensus on the Diagnosis and Treatment of NRG1/2 Gene Fusion Solid Tumors
Chunwei Xu, Qian Wang, Dong Wang, Wenxian Wang, Wenfeng Fang, Ziming Li, Aijun Liu, Jinpu Yu, Wenzhao Zhong, Zhijie Wang, Yongchang Zhang, Jingjing Liu, Shirong Zhang, Xiuyu Cai, Anwen Liu, Wen Li, Ping Zhan, Hongbing Liu, Tangfeng Lv, Liyun Miao, Lingfen
Global Medical Genetics.2024; 11(01): 086. CrossRef
Analysis on the pathogenesis and treatment progress of NRG1 fusion-positive non-small cell lung cancer
Hongyan Li, Lina Xu, Hongshun Cao, Tianyi Wang, Siwen Yang, Yixin Tong, Linlin Wang, Qiang Liu
Frontiers in Oncology.2024;[Epub] CrossRef
Analysis of CD74 Occurrence in Oncogenic Fusion Proteins
Jasmine Vargas, Georgios Pantouris
International Journal of Molecular Sciences.2023; 24(21): 15981. CrossRef

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