Gastrointestinal and liver oncology-radiotherapy unit, institut Sainte-Catherine, chemin du Lavarin, 84000 Avignon, France.
Clin Res Hepatol Gastroenterol. 2011 Feb;35(2):125-31. doi: 10.1016/j.gcb.2009.11.005. Epub 2010 Nov 25.
Irinotecan (CPT11) at 180 mg/m(2) with LV5FU2 for metastatic colorectal cancer (MCRC) has response rates (RRs) of 56 and 4% as first- and second-line treatments, respectively [1-2], and higher doses of CPT11 result in higher RRs. The present cohort analysis aimed to evaluate the effect of increasing doses of this combination treatment in clinical practice.
Chemo-naive and pretreated patients with MCRC received CPT11 and LV5FU2 (5FU 48-h CI 2400 mg/m(2), D1 bolus leucovorin 200 mg/m(2)), followed by 5FU 400 mg/m(2) (cycles d1-d15). CPT11 dose was increased by 20 mg/m(2) at each cycle, from 180 mg/m(2) up to 260 mg/m(2), unless grade 3 toxicities other than alopecia arose.
Between March 2002 and September 2005, 46 patients were recruited (median age: 62.3 years). A total of 512 cycles of chemotherapy were administered (median: 9 cycles/patient; range: 3-41). Median follow-up was 16.2 months. Altogether, 27 patients had received prior chemotherapy: 24 with an oxaliplatin-based regimen; seven with CPT11; and five with LV5FU2 or oral 5FU. Doses of 260 mg/m(2) were used in 17 patients, 240 mg/m(2) in seven, 220 mg/m(2) in six and 200 mg/m(2) in five, while 11 remained at 180 mg/m(2); 121 cycles used 260 mg/m(2) (24%), with 76 cycles at 240 mg/m(2) (14%), 78 cycles at 220 mg/m(2) and 58 cycles at 200mg/m(2). The objective response (OR) was 40%, with stable disease (SD) in 45% and disease progression (DP) in 11%. In the first-line therapy group, partial/complete responses were 55%, with SD in 30% and DP in 15%. In pretreated patients, OR was 30.5%, SD was 58.5% and DP was 11%. Nine patients (20%) had a therapeutic break (median: 5.1 months; range: 3-10). Overall median survival was 17 months, with 16.5 months in pretreated patients and 19.6 months in the first-line group. Toxicity grades 3-4 and overall incidence per cycle were: neutropenia, 3-22%; diarrhea, 4-22%; vomiting, 2-20%; alopecia, 20-26%; anemia, 0.2-2%; thrombocytopenia, 0-0%; and mucositis, 0.4-2.2%.
The toxicity of high-dose CPT11+LV5FU2 chemotherapy was well tolerated when the dose was progressively increased according to individual tolerability, with 37% of patients receiving CPT11 at 260 mg/m(2). Progression-free survival (PFS) increased with higher doses of CPT11. In the chemo-naive and pretreated subgroups, the median PFS was 10.9 and 8.8 months, respectively (P=0.698, NS). Optimization of CPT11 doses in pretreated patients appears to pave the way for new treatment options.
伊立替康（CPT11）联合亚叶酸钙和 5-氟尿嘧啶（LV5FU2）治疗转移性结直肠癌（MCRC），一线和二线治疗的缓解率（RR）分别为 56%和 4%[1-2]，且更高剂量的 CPT11 可提高 RR。本队列分析旨在评估在临床实践中增加该联合治疗剂量的效果。
接受 CP1T11 和 LV5FU2（5FU 48 小时持续输注 2400mg/m2，D1 推注亚叶酸钙 200mg/m2）治疗的初治和经治 MCRC 患者，随后给予 5FU 400mg/m2（周期 d1-d15）。CPT11 剂量每周期增加 20mg/m2，从 180mg/m2 增加到 260mg/m2，除非出现除脱发以外的 3 级毒性。
2002 年 3 月至 2005 年 9 月，共纳入 46 例患者（中位年龄：62.3 岁）。共接受 512 个周期的化疗（中位：9 个周期/患者；范围：3-41）。中位随访时间为 16.2 个月。共有 27 例患者接受过先前的化疗：24 例接受奥沙利铂为基础的方案；7 例接受 CPT11；5 例接受 LV5FU2 或口服 5FU。17 例患者使用 260mg/m2 剂量，7 例患者使用 240mg/m2 剂量，6 例患者使用 220mg/m2 剂量，5 例患者使用 200mg/m2 剂量，11 例患者仍使用 180mg/m2 剂量；121 个周期使用 260mg/m2（24%），76 个周期使用 240mg/m2（14%），78 个周期使用 220mg/m2，58 个周期使用 200mg/m2。客观缓解（OR）为 40%，稳定疾病（SD）为 45%，疾病进展（DP）为 11%。在一线治疗组中，部分/完全缓解率为 55%，SD 为 30%，DP 为 15%。在经治患者中，OR 为 30.5%，SD 为 58.5%，DP 为 11%。9 例（20%）患者进行了治疗中断（中位：5.1 个月；范围：3-10）。总体中位生存期为 17 个月，经治患者为 16.5 个月，一线治疗组为 19.6 个月。毒性分级 3-4 级和每个周期的总体发生率为：中性粒细胞减少症，3-22%；腹泻，4-22%；呕吐，2-20%；脱发，20-26%；贫血，0.2-2%；血小板减少症，0-0%；和粘膜炎，0.4-2.2%。
当根据个体耐受性逐渐增加 CPT11 剂量时，高剂量 CPT11+LV5FU2 化疗的毒性是可以耐受的，37%的患者接受 260mg/m2 的 CPT11。CPT11 剂量越高，无进展生存期（PFS）越长。在初治和经治亚组中，中位 PFS 分别为 10.9 和 8.8 个月（P=0.698，NS）。在经治患者中优化 CPT11 剂量似乎为新的治疗选择铺平了道路。
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