Riluzole in Combination with mFOLFOX6 and Bevacizumab in Treating Patients with Metastatic Colorectal Cancer: A Phase 1 Clinical Trial

IF 10 1区医学 Q1 ONCOLOGY

Clinical Cancer Research Pub Date : 2025-03-21 DOI:10.1158/1078-0432.ccr-24-3964

Chunjie Li, Anne M. Noonan, John Hays, Sameek Roychowdhury, Pannaga Malalur, Rifat Elkhatib, Ashish Manne, Arjun Mittra, Shafia Rahman, Liwei Yan, Kasey Hill, Nicole Abbott, Mitch Phelps, Joo Young Na, Beiyuan Liang, Hayden Storts, Misbah Khan, Evan H. Zhang, Wayne Miles, Vedat Yildiz, Lai Wei, Jing J. Wang, Ning Jin

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引用次数: 0

Abstract

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the US. 5-fluorouracil (5-FU)-based chemotherapies in combination with targeted agents remain the standard of care in patients with metastatic or locally advanced disease. New treatment strategies are needed for metastatic CRC patients with microsatellite stable disease. Preclinical studies showed that riluzole, an oral medicine for amyotrophic lateral sclerosis, inhibits glutamate release and synergizes with 5-FU to reduce cell viability in CRC cell lines. METHODS: In this single-arm, phase 1 trial of riluzole in combination with mFOLFOX6/bevacizumab for patients with metastatic CRC, the riluzole dose started at 50 mg twice daily, escalating to 100 mg twice daily or de-escalating to 50 mg once daily. Patients received riluzole for 16 weeks in combination with mFOLOFX6/bevacizumab for 8 cycles. Patients then either continued mFOLFOX6/bevacizumab or switched therapy. RESULTS: Twelve of the 14 patients enrolled were evaluable. All patients previously received FOLFOX, and 5 patients (41.7%) showed disease resistance to it. Two patients obtained partial responses, 9 had stable disease, and 1 had progressive disease. The objective response rate was 16.7%, and the disease control rate was 91.7%. The median duration of response was 4.9 months (95% CI 1.6-9.8). Median progression-free survival and overall survival were 4.89 and 12.98 months, respectively. CONCLUSION: Our study showed that riluzole plus mFOLFOX6/bevacizumab is well tolerated in patients with metastatic CRC and may have clinical activity in patients whose disease is resistant to FOLFOX.

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利鲁唑联合 mFOLFOX6 和贝伐单抗治疗转移性结直肠癌患者：一期临床试验

背景：结直肠癌（CRC）是美国癌症相关死亡的第二大原因。以5-氟尿嘧啶（5-FU）为基础的化疗联合靶向药物仍然是转移性或局部晚期疾病患者的标准治疗方案。转移性结直肠癌微卫星稳定型患者需要新的治疗策略。临床前研究表明，治疗肌萎缩性侧索硬化症的口服药物利鲁唑可抑制谷氨酸释放，并与5-FU协同降低CRC细胞系的细胞活力。方法：在这项将利鲁唑联合mFOLFOX6/贝伐单抗治疗转移性结直肠癌患者的单组1期试验中，利鲁唑的剂量开始为50mg，每日两次，逐渐增加到100mg，每日两次，或逐渐减少到50mg，每日一次。患者接受利鲁唑联合mFOLOFX6/贝伐单抗治疗16周，共8个周期。然后，患者要么继续使用mFOLFOX6/贝伐单抗，要么转换治疗。结果：入组的14例患者中有12例可评估。所有患者既往均接受FOLFOX治疗，5例患者（41.7%）出现疾病耐药。2例获得部分缓解，9例病情稳定，1例病情进展。客观有效率为16.7%，疾病控制率为91.7%。中位反应持续时间为4.9个月（95% CI 1.6-9.8）。中位无进展生存期和总生存期分别为4.89个月和12.98个月。结论：我们的研究表明，利鲁唑联合mFOLFOX6/贝伐单抗在转移性结直肠癌患者中具有良好的耐受性，并且可能在对folfox6耐药的患者中具有临床活性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Cancer Research 医学-肿瘤学

CiteScore

20.10

自引率

1.70%

发文量

1207

审稿时长

2.1 months

期刊介绍： Clinical Cancer Research is a journal focusing on groundbreaking research in cancer, specifically in the areas where the laboratory and the clinic intersect. Our primary interest lies in clinical trials that investigate novel treatments, accompanied by research on pharmacology, molecular alterations, and biomarkers that can predict response or resistance to these treatments. Furthermore, we prioritize laboratory and animal studies that explore new drugs and targeted agents with the potential to advance to clinical trials. We also encourage research on targetable mechanisms of cancer development, progression, and metastasis.