Koonrungsesomboon Nut, Teeyakasem Pimpisa, Dukaew Nahathai, Sirikaew Nutnicha, Thongkumkoon Patcharawadee, Yongpitakwattana Petlada, Thepbundit Viraporn, Chaiyawat Parunya, Klangjorhor Jeerawan, Sakuludomkan Chotiwit, Charoentum Chaiyut, Chewaskuyong Busyamas, Sathitsamitphong Lalita, Kiatisevi Piya, Sunpaweravong Patrapim, Sathitruangsak Chirawadee, Pruksakorn Dumnoensun
Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
Center of Multidisciplinary Technologies for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
Int J Clin Oncol. 2025 Sep 12. doi: 10.1007/s10147-025-02877-0.
Osteosarcoma is a prevalent and aggressive bone malignancy primarily affecting young adults. Despite advances in standard treatment, the 5-year survival rate remains low, highlighting the need for new chemotherapy options. Mycophenolate mofetil, an immunosuppressant used post-transplant, has shown promising preclinical anticancer effects in osteosarcoma, warranting further investigation for potential repurpose in humans.
We conducted this proof-of-concept phase II clinical trial to assess the efficacy and safety of mycophenolate mofetil in high-grade locally advanced or metastatic osteosarcoma. Patients received 3-5 g/day mycophenolate mofetil for four 28-day cycles or until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) at 16 weeks. Secondary endpoints included overall survival (OS), overall response rate, safety, pharmacokinetics, pain score, and quality of life.
Fifteen patients were enrolled. Due to intolerable toxicity at higher doses, most patients received 3 g/day of mycophenolate mofetil. At 16 weeks, the PFS rate was 40%, with only one patient (6.7%) achieving stable disease. Median PFS and OS were 70 and 301 days, respectively. The most common grade 3-4 adverse events were anemia and fatigue, each occurring in 20% of patients. Pharmacokinetic analysis revealed high interindividual variability.
Although mycophenolate mofetil at 3 g/day was well tolerated, it did not meet expectations for anticancer efficacy in patients with high-grade locally advanced or metastatic osteosarcoma. This study should be considered a negative trial. Further research is needed to explore the therapeutic role of mycophenolate mofetil through alternative strategies or identify more effective interventions for osteosarcoma.
骨肉瘤是一种常见且侵袭性强的骨恶性肿瘤，主要影响年轻人。尽管标准治疗取得了进展，但5年生存率仍然很低，这凸显了对新化疗方案的需求。霉酚酸酯是一种移植后使用的免疫抑制剂，在骨肉瘤的临床前抗癌效果方面显示出有前景的结果，值得进一步研究其在人类中的潜在新用途。
我们开展了这项概念验证性II期临床试验，以评估霉酚酸酯在高级别局部晚期或转移性骨肉瘤中的疗效和安全性。患者接受每天3 - 5克霉酚酸酯，共四个28天周期，或直至疾病进展或出现不可接受的毒性。主要终点是16周时的无进展生存期（PFS）。次要终点包括总生存期（OS）、总缓解率、安全性、药代动力学、疼痛评分和生活质量。
招募了15名患者。由于高剂量时出现无法耐受的毒性，大多数患者接受了每天3克的霉酚酸酯。在16周时，PFS率为40%，只有一名患者（6.7%）病情稳定。中位PFS和OS分别为70天和301天。最常见的3 - 4级不良事件是贫血和疲劳，各有20%的患者发生。药代动力学分析显示个体间差异很大。
尽管每天3克的霉酚酸酯耐受性良好，但在高级别局部晚期或转移性骨肉瘤患者中，其抗癌疗效未达预期。本研究应被视为一项阴性试验。需要进一步研究通过替代策略探索霉酚酸酯的治疗作用，或为骨肉瘤确定更有效的干预措施。
