Radioembolization of liver metastases from colorectal cancer using yttrium-90 microspheres with concomitant systemic oxaliplatin, fluorouracil, and leucovorin chemotherapy
Radioembolization of liver metastases from colorectal cancer using yttrium-90 microspheres with concomitant systemic oxaliplatin, fluorouracil, and leucovorin chemotherapy
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DOI：
10.1200/jco.2006.08.7916
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发表时间：
2007-03-20
影响因子：
45.3
通讯作者：
Steward, William P.
中科院分区：
文献类型：
--
作者：
Sharma, Ricky A.;Van Hazel, Guy A.;Steward, William P.
目的肝转移是晚期结直肠癌（CRC）患者死亡的主要原因。将含有β-发射体钇-90的树脂微球（SIR Spheres）注射到肝脏动脉供应中可引起转移瘤的放射性栓塞。这种治疗还没有测试与放射增敏化疗，奥沙利铂，这似乎协同治疗CRC时，与氟尿嘧啶和甲酰四氢叶酸（FOLFOX）。患者和方法的SIR-Spheres治疗与改良FOLFOX 4全身化疗的I期研究进行了不可手术的肝转移的CRC谁以前没有接受过化疗转移性疾病的患者。前3个周期给予奥沙利铂（30 - 85 mg/m2），从第4周期至第12周期给予FOLFOX 4全剂量。结果20例患者入组本研究。5例患者出现国家癌症研究所（NCI; Bethesda，MD）3级腹痛，其中2例出现微球诱导的胃溃疡。剂量限制性毒性为3级或4级中性粒细胞减少，在12例患者中记录。记录了1起一过性3级肝毒性事件。方案治疗6个月后，平均脾脏体积增加了92%。18例患者部分缓解，2例患者病情稳定。2例患者在方案治疗后接受了部分肝切除术。中位无进展生存期为9.3个月，中位肝脏疾病进展时间为12.3个月。结论前3个周期奥沙利铂的最大耐受剂量为60 mg/m2，此后为全剂量FOLFOX 4。这种放化疗方案值得在II-III期试验中进行评价。
Purpose Liver metastases represent the principal cause of death in patients with advanced colorectal cancer (CRC). Injection of resin microspheres (SIR Spheres) - containing the beta-emitter, yttrium-90 - into the arterial supply of the liver can cause radioembolization of metastases. This treatment has not been tested with the radiosensitizing chemotherapy, oxaliplatin, which appears synergistic in the treatment of CRC when combined with fluorouracil and leucovorin (FOLFOX).Patients and Methods A phase I study of SIR-Spheres therapy with modified FOLFOX4 systemic chemotherapy was conducted in patients with inoperable liver metastases from CRC who had not previously received chemotherapy for metastatic disease. Oxaliplatin (30 to 85 mg/m(2)) was administered for the first three cycles with full FOLFOX4 doses from cycle 4 until cycle 12. The primary end point was toxicity.Results Twenty patients were enrolled onto the study. Five patients experienced National Cancer Institute (NCI; Bethesda, MD) grade 3 abdominal pain, two of whom had microsphere-induced gastric ulcers. The dose-limiting toxicity was grade 3 or 4 neutropenia, which was recorded in 12 patients. One episode of transient grade 3 hepatotoxicity was recorded. Mean splenic volume increased by 92% following 6 months of protocol therapy. Partial responses were demonstrated in 18 patients and stable disease in two patients. Two patients underwent partial hepatic resection following protocol therapy. Median progression-free survival was 9.3 months, and median time to progression in the liver was 12.3 months.Conclusion The maximum-tolerated dose was 60 mg/m(2) of oxaliplatin for the first three cycles, with full FOLFOX4 doses thereafter. This chemoradiation regime merits evaluation in phase II-III trials.