Masi G, Allegrini G, Cupini S, Marcucci L, Cerri E, Brunetti I, Fontana E, Ricci S, Andreuccetti M, Falcone A
Division of Medical Oncology, Department of Oncology, Hospital of Livorno and University of Pisa, Italy.
Ann Oncol. 2004 Dec;15(12):1766-72. doi: 10.1093/annonc/mdh470.
In a previous phase I-II study we demonstrated that the FOLFOXIRI regimen [irinotecan 125-175 mg/m2 day 1, oxaliplatin 100 mg/m2 day 1, l-leucovorin (l-LV) 200 mg/m2 day 1, 5-fluorouracil (5-FU) 3800 mg/m2 as a 48-h chronomodulated continuous infusion starting on day 1, repeated every 2 weeks] has promising activity and efficacy in metastatic colorectal cancer. However, this regimen required a chronomodulated infusion of 5-FU, and because neutropenia occurred in 32% of cycles, granulocyte colony-stimulating factor (G-CSF) was used and the delivered dose intensity was only approximately 78% of planned. Therefore, we conducted the present phase II study in order to develop a simplified FOLFOXIRI regimen that could be more easily administered in clinical practice as well as in multicenter settings.
A total of 32 patients with unresectable metastatic colorectal cancer received irinotecan 165 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, l-LV 200 mg/m2 day 1 and 5-FU 3200 mg/m2 as a 48-h continuous (not chronomodulated) infusion starting on day 1, repeated every 2 weeks.
All 32 patients were evaluated for safety and the incidence of grade 3-4 toxic effects, and the use of G-CSF seemed to be lower than with the previous FOLFOXIRI regimen: grade 4 neutropenia (34%), grade 3 diarrhea (16%), grade 3 stomatitis (6%) and grade 2-3 peripheral neurotoxicity (37%) were reported, and G-CSF was used in 23% of cycles. Delivered dose intensity was 88% of that planned, and no toxic deaths occurred. The intention-to-treat analysis for activity showed four complete responses, 19 partial responses, seven stable disease and two progressive disease, for an overall response rate of 72% (95% confidence interval 53% to 86%). Eight (25%) patients with residual liver or lung metastases were radically resected after chemotherapy. After a median follow-up of 18.1 months, the median progression-free survival is 10.8 months and median survival is 28.4 months.
This simplified FOLFOXIRI combination can be delivered easily in outpatient settings, with manageable toxic effects, and has very promising antitumor activity. While the safety profile seems to be improved in comparison with our previous FOLFOXIRI regimen, antitumor activity and efficacy appear to be maintained.
在之前的一项I-II期研究中，我们证明了FOLFOXIRI方案[伊立替康125 - 175mg/m²第1天，奥沙利铂100mg/m²第1天，左亚叶酸（l-LV）200mg/m²第1天，5-氟尿嘧啶（5-FU）3800mg/m²从第1天开始进行48小时时间调节的持续静脉输注，每2周重复一次]在转移性结直肠癌中具有可观的活性和疗效。然而，该方案需要对5-FU进行时间调节输注，并且由于32%的周期出现了中性粒细胞减少，使用了粒细胞集落刺激因子（G-CSF），实际给药剂量强度仅约为计划的78%。因此，我们开展了本项II期研究，以开发一种简化的FOLFOXIRI方案，使其在临床实践以及多中心环境中更易于给药。
共有32例无法切除的转移性结直肠癌患者接受伊立替康165mg/m²第1天，奥沙利铂85mg/m²第1天，l-LV 200mg/m²第1天，以及5-FU 3200mg/m²从第1天开始进行48小时持续（非时间调节）静脉输注，每2周重复一次。
对所有32例患者进行了安全性评估以及3 - 4级毒性反应发生率评估，G-CSF的使用似乎低于之前的FOLFOXIRI方案：报告的4级中性粒细胞减少（34%）、3级腹泻（16%）、3级口腔炎（6%）和2 - 3级周围神经毒性（37%），23%的周期使用了G-CSF。实际给药剂量强度为计划的88%，未发生毒性死亡。意向性分析显示有4例完全缓解、19例部分缓解、7例病情稳定和2例病情进展，总缓解率为72%（95%置信区间53%至86%）。8例（25%）有肝脏或肺部残留转移灶的患者在化疗后接受了根治性切除。中位随访18.1个月后，中位无进展生存期为10.8个月，中位生存期为28.4个月。
这种简化的FOLFOXIRI联合方案在门诊环境中易于给药，毒性反应可控，并且具有非常可观的抗肿瘤活性。虽然与我们之前的FOLFOXIRI方案相比安全性似乎有所改善，但抗肿瘤活性和疗效似乎得以维持。
