Phase I/II study of sequential therapy with irinotecan and S-1 for metastatic colorectal cancer.
Phase I/II study of sequential therapy with irinotecan and S-1 for metastatic colorectal cancer.
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DOI：
10.1038/sj.bjc.6605432
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发表时间：
2009-12-15
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
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作者：
伊立替康（CPT-11）和S-1对结直肠癌均有活性；但由于S-1是5-氟尿嘧啶（5-FU）的前药，5-FU及其代谢物可能会抑制CPT-11的抗肿瘤作用。因此，我们设计了顺序组合，在第1天输注CPT-11，每3周在第3 - 16天口服S-1，每天80 mg m−2。12名患者进入I期研究，推荐剂量确定为CPT-11剂量为150 mg m - 2， S-1剂量为80 mg m - 2。总共有36名患者进入了II期研究，其中4名和16名患者有完全和部分缓解。总有效率为55.6%(95%可信区间，38.1-72.1%)，中位无进展生存期为7.7个月（95%可信区间，4.8-12.6个月）。3级中性粒细胞减少是最常见的血液学毒性，在215个疗程中发生6.5%。3级非血液学毒性包括厌食症（1.4%）和腹泻（0.9%）。没有任何形式的4级毒性。我们的研究结果表明，与传统方案相比，该方案对转移性结直肠癌患者方便、安全且有希望。
Both irinotecan (CPT-11) and S-1 are active against colorectal cancer; however, as S-1 is a prodrug of 5-fluorouracil (5-FU), 5-FU and its metabolites might inhibit the antitumour effect of CPT-11. Therefore, we designed a sequential combination, in which CPT-11 infusion was given on day 1 and S-1 was given orally at 80 mg m−2 per day on days 3–16 every 3 weeks. Twelve patients entered the phase I study, and the recommended doses were determined as a CPT-11 dose of 150 mg m−2 and an S-1 dose of 80 mg m−2. In all, 36 patients entered the phase II study, of whom 4 and 16 had complete and partial responses. The overall response rate was 55.6% (95% confidence interval, 38.1–72.1%), and median progression-free survival was 7.7 months (95% confidence interval, 4.8–12.6 months). Grade 3 neutropenia was the most common haematological toxicity and occurred in 6.5% of 215 treatment courses. Grade 3 non-haematological toxicities included anorexia (1.4%) and diarrhoea (0.9%). There was no grade 4 toxicity of any kind. Our results suggest that this regimen is convenient, safe and promising, compared with conventional regimens for patients with metastatic colorectal cancer.