Boige Valérie, Malka David, Elias Dominique, Castaing Marine, De Baere Thierry, Goere Diane, Dromain Clarisse, Pocard Marc, Ducreux Michel
Department of Medicine, Institut Gustave Roussy, Villejuif, France.
Ann Surg Oncol. 2008 Jan;15(1):219-26. doi: 10.1245/s10434-007-9581-7. Epub 2007 Sep 26.
We have previously shown promising activity of hepatic arterial infusion (HAI) oxaliplatin combined with intravenous (IV) 5-fluorouracil (5-FU) and leucovorin (LV) as first-line chemotherapy in patients with colorectal liver metastases (CRLM) (intent-to-treat [ITT] objective response rate [ORR], 64%; secondary resection rate, 18%; overall survival [OS], 27 months). Whether this regimen could be beneficial after systemic chemotherapy failure is unknown.
Patients with unresectable CRLM and history of systemic chemotherapy failure were treated bimonthly with HAI oxaliplatin (100 mg/m(2) 2 hours) combined with IV LV and IV bolus and infusional 5FU (modified LV5FU2 regimen).
Forty-four consecutive patients (median age 56 years; median number of prior systemic chemotherapy regimens, 2 range 1-5) were included, of whom 43 (98%) had previously received oxaliplatin (n = 34), irinotecan (n = 37), or both (n = 28). Patients received a median of nine cycles of HAI oxaliplatin and IV modified LV5FU2 (range 0-25). Toxicity included grade 3-4 neutropenia (43%), grade 2-3 neuropathy (43%), and grade 3-4 abdominal pain (14%). We observed 24 partial ORs (62%) among the 39 assessable patients (ITT ORR, 55%; 95% CI, 40-69%), including 17, 12, and 12 patients who had failed to respond to prior systemic chemotherapy with FOLFIRI, FOLFOX, or both, respectively. Tumor response allowed further R0 surgical resection (n = 7) or radiofrequency ablation (n = 1) of initially unresectable CRLM in eight patients (18%). Median progression-free survival and OS were 7 and 16 months, respectively.
HAI oxaliplatin and IV LV5FU2 is feasible, safe, and shows promising activity after systemic chemotherapy failure, allowing surgical resection of initially unresectable CRLM in 18% of patients.
我们之前已经表明，肝动脉灌注（HAI）奥沙利铂联合静脉注射（IV）5-氟尿嘧啶（5-FU）和亚叶酸钙（LV）作为一线化疗方案，在结直肠癌肝转移（CRLM）患者中显示出有前景的活性（意向性治疗[ITT]客观缓解率[ORR]为64%；二次切除率为18%；总生存期[OS]为27个月）。该方案在全身化疗失败后是否有益尚不清楚。
对患有不可切除的CRLM且有全身化疗失败史的患者，每两个月给予HAI奥沙利铂（100mg/m²，持续2小时）联合IV亚叶酸钙以及IV推注和持续输注5-FU（改良LV5FU2方案）进行治疗。
纳入了44例连续患者（中位年龄56岁；既往全身化疗方案的中位数量为2，范围1 - 5），其中43例（98%）之前接受过奥沙利铂（n = 34）、伊立替康（n = 37）或两者（n = 28）治疗。患者接受HAI奥沙利铂和IV改良LV5FU2的中位周期数为9个周期（范围0 - 25）。毒性反应包括3 - 4级中性粒细胞减少（43%）、2 - 3级神经病变（43%）和3 - 4级腹痛（14%）。在39例可评估患者中，我们观察到24例部分缓解（62%）（ITT ORR为55%；95%CI，40% - 69%），其中分别有17例、12例和12例患者之前对FOLFIRI、FOLFOX或两者的全身化疗无反应。肿瘤缓解使得8例患者（18%）对最初不可切除的CRLM进行了进一步的R0手术切除（n = 7）或射频消融（n = 1）。中位无进展生存期和OS分别为7个月和16个月。
HAI奥沙利铂和IV LV5FU2是可行、安全的，并且在全身化疗失败后显示出有前景的活性，使18%的患者对最初不可切除的CRLM进行了手术切除。
