伊立替康、5-氟尿嘧啶和左亚叶酸联合治疗（改良Saltz方案）用于转移性结直肠癌患者的I/II期研究。

Phase I/II study of irinotecan, 5-fluorouracil, and l-leucovorin combination therapy (modified Saltz regimen) in patients with metastatic colorectal cancer.

作者信息

Goto Ayumu, Yamada Yasuhide, Hosokawa Ayumu, Ura Takashi, Arai Tatsuhiro, Hamaguchi Tetsuya, Muro Kei, Shimada Yasuhiro, Shirao Kuniaki

机构信息

Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

出版信息

Int J Clin Oncol. 2004 Oct;9(5):364-8. doi: 10.1007/s10147-004-0407-3.

DOI:10.1007/s10147-004-0407-3

PMID:15549585

Abstract

BACKGROUND

A combination of irinotecan 125 mg/m2, 5-fluorouracil (5-FU) 500 mg/m2, and leucovorin (LV) 20 mg/m2 (Saltz regimen; treatment on days 1, 8, 15, and 22 every 6 weeks) is widely used for the treatment of metastatic colorectal cancer. A modified schedule with chemotherapy on days 1 and 8 of a 21-day cycle was recommended in 2001 because of early treatment-related mortality. We conducted a phase I/II study of this modified Saltz regimen as first-line therapy in Japanese patients with metastatic colorectal cancer to assess the maximum tolerated dose (MTD) and the recommended dose of 5-FU when given with fixed doses of l-LV and irinotecan, and to evaluate the efficacy and the feasibility of this regimen.

METHODS

Irinotecan, 5-FU, and l-LV were administered on days 1 and 8 of a 21-day cycle. Irinotecan 100 mg/m2 was given intravenously over the course of 90 min on day 1, followed by l-LV 10 mg/m2, and then 5-FU. The dose of 5-FU was escalated from 400 mg/m2 (level 1) to 500 mg/m2 (level 2). If neither level met the criteria for the MTD, the recommended dose was defined as level 2, and dose escalation was discontinued, because the maximum approved weekly dose of irinotecan alone in Japan is 100 mg/m2 and the dose of 5-FU in the original Saltz regimen was 500 mg/m2.

RESULTS

One patient had grade 4 neutropenia with fever at level 1, and four patients had grade 3 neutropenia at level 2. There was no treatment-related death. Level 2 did not meet the criteria for the MTD. The relative dose intensities of the first five cycles were 91% for both 5-FU and irinotecan at level 1 and 86% for 5-FU and 93% for irinotecan at level 2. The response rates were 58% for all patients, and 69% for patients at level 2. CONCLUSION. Our results confirm that the modified Saltz regimen is safe and efficacious for Japanese patients. The recommended doses for phase II studies are irinotecan 100 mg/m2, 5-FU 500 mg/m2, and l-LV 10 mg/m2.

摘要

背景

伊立替康125mg/m²、5-氟尿嘧啶（5-FU）500mg/m²和亚叶酸钙（LV）20mg/m²的联合方案（萨尔茨方案；每6周在第1、8、15和22天进行治疗）被广泛用于治疗转移性结直肠癌。由于早期治疗相关死亡率，2001年推荐了一种在21天周期的第1天和第8天进行化疗的改良方案。我们开展了一项针对日本转移性结直肠癌患者的I/II期研究，以评估这种改良萨尔茨方案作为一线治疗时的最大耐受剂量（MTD）以及与固定剂量的左旋亚叶酸钙和伊立替康联合使用时5-FU的推荐剂量，并评估该方案的疗效和可行性。

方法

伊立替康、5-FU和左旋亚叶酸钙在21天周期的第1天和第8天给药。第1天，伊立替康100mg/m²在90分钟内静脉输注，随后是左旋亚叶酸钙10mg/m²，然后是5-FU。5-FU的剂量从400mg/m²（1级）逐步增加到500mg/m²（2级）。如果两个级别均未达到MTD标准，则将推荐剂量定义为2级，并停止剂量递增，因为在日本，伊立替康单独使用时的最大批准每周剂量为100mg/m²，且原始萨尔茨方案中5-FU的剂量为500mg/m²。

结果

1例患者在1级时出现4级中性粒细胞减少伴发热，4例患者在2级时出现3级中性粒细胞减少。没有治疗相关死亡。2级未达到MTD标准。前五个周期中，5-FU和伊立替康在1级时的相对剂量强度均为91%，在2级时5-FU为86%，伊立替康为93%。所有患者的缓解率为58%，2级患者的缓解率为69%。结论。我们的结果证实，改良萨尔茨方案对日本患者安全有效。II期研究的推荐剂量为伊立替康100mg/m²、5-FU 500mg/m²和左旋亚叶酸钙10mg/m²。