Senseki Hospital, 57-3 Akai, Higashimatsushima, Miyagi, 981-0501, Japan.
Int J Clin Oncol. 2012 Apr;17(2):150-4. doi: 10.1007/s10147-011-0272-9. Epub 2011 Jul 26.
This study was intended to ascertain the feasibility of a combination therapy with irinotecan by 24-h intravenous infusion (24-h CPT-11) and 5-fluorouracil (5-FU) for patients with metastatic colorectal cancer, to estimate the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD), to determine the recommended dose (RD) for the Phase II study, and to evaluate the efficacy of the combination therapy.
The dosage regimen was as follows: CPT-11 was given by 24-h CPT-11 on day 1, followed by 24-h intravenous infusion of 5-FU on day 2. This regimen was repeated every 2 weeks. The dose of CPT-11 was escalated in five steps from 50 to 75, 100, 125, or 150 mg/m(2) (levels 1-5), whereas the dose of 5-FU was fixed at 800 mg/m(2).
Twenty-six patients were recruited for this study, and 25 of the 26 patients were eligible for the assessment. The DLTs of 24-h CPT-11/5-FU therapy included grade 3 diarrhea in 1 patient treated at level 1, and grade 3 neutropenia in 1 patient and grade 4 neutropenia in 1 patient at level 4. In level 5, in 3 cases the next administration could not be done for 22 days or more as a consequence of anorexia. Thus, the level 5 was made a MTD and the level 4 was made a RD. The main side effects of grade 3 or higher, although nausea/vomiting occurred, were mild and tolerable in severity overall. The overall response rate was 24.0% (6PR/25).
This study suggests that 24-h CPT-11/5-FU therapy is feasible and effective for treatment of metastatic colorectal cancer.
本研究旨在确定伊立替康持续 24 小时静脉输注（24-hCPT-11）联合氟尿嘧啶（5-FU）治疗转移性结直肠癌患者的联合治疗的可行性，评估剂量限制毒性（DLT）和最大耐受剂量（MTD），确定用于 II 期研究的推荐剂量（RD），并评估联合治疗的疗效。
治疗方案如下：CPT-11 于第 1 天持续 24 小时输注，随后第 2 天持续 24 小时输注 5-FU。该方案每 2 周重复一次。CPT-11 的剂量分 5 个阶段从 50mg/m2 增加到 75、100、125 或 150mg/m2（水平 1-5），而 5-FU 的剂量固定在 800mg/m2。
本研究共招募了 26 例患者，26 例患者中有 25 例符合评估条件。24-hCPT-11/5-FU 治疗的 DLT 包括 1 例患者在 1 级时出现 3 级腹泻，1 例患者在 4 级时出现 3 级中性粒细胞减少症和 1 例患者出现 4 级中性粒细胞减少症。在 5 级，由于厌食，有 3 例患者的下一次给药不能超过 22 天。因此，将 5 级确定为 MTD，将 4 级确定为 RD。尽管恶心/呕吐等 3 级或更高的主要副作用发生，但总体上是轻微且可耐受的。总缓解率为 24.0%（6PR/25）。
本研究表明，24-hCPT-11/5-FU 治疗转移性结直肠癌是可行且有效的。
