每周大剂量5-氟尿嘧啶24小时输注联合亚叶酸钙（AIO方案）加伊立替康用于转移性结直肠癌（CRC）的二线及序贯治疗

Weekly High-dose 5-Fluorouracil as 24-hour Infusion Combined with Sodium Folinic Acid (AIO regimen) Plus Irinotecan in Second-line and Sequential Therapy of Metastatic Colorectal Cancer (CRC).

作者信息

Wein Axel, Siebler Juergen, Wolff Kerstin, Ostermeier Nicola, Busse Dagmar, Hagel Alexander, Koch Franz, Merx Kirsten, Neurath Markus Friedrich, Hofheinz Ralf-Dieter

机构信息

Department of Internal Medicine 1, Gastroenterology, Pneumology, and Endocrinology, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany

Department of Internal Medicine 1, Gastroenterology, Pneumology, and Endocrinology, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany.

出版信息

Anticancer Res. 2017 Jul;37(7):3771-3779. doi: 10.21873/anticanres.11752.

DOI:10.21873/anticanres.11752

PMID:28668873

Abstract

BACKGROUND/AIM: The aim of this work was to evaluate the efficacy and safety of second-line treatment with weekly high-dose 5-fluorouracil (5-FU) as a 24-hour infusion (24-h inf.) combined with sodium folinic acid (FA) (AIO-regimen) plus irinotecan (Iri.) after pretreatment with AIO-regimen plus oxaliplatin (L-OHP).

PATIENTS AND METHODS

Patients with non-resectable distant CRC metastases were enrolled in a prospective phase II study for palliative second-line treatment after previous progression of first-line treatment in accordance with the AIO-regimen plus oxaliplatin. On an outpatient basis, the patients received a treatment regimen comprising of weekly 80 mg/m irinotecan in the form of a 1-hour i.v. infusion and 2,000 mg/m 5-FU combined with 500 mg/m sodium folinic acid administered as a 24-h infusion i.v. once weekly.

RESULTS

During second-line treatment, a total of 59 patients received 520 chemotherapy applications. As the main higher-grade symptom of toxicity, diarrhea (NCI-CTC-toxicity grade 3) presented in 8 patients (13.6%, 95%CI=5.1-23.7), followed by leukocytopenia (CTC grade 3) in 3 patients (5.1%, 95%CI=0-11.9), followed by thrombocytopenia (CTC grade 3) in 1 patient (1.7%, 95%CI=0-5.1). Fifty-nine patients were evaluable for treatment response. The remission data can be summarized as follows: complete remission (CR); n=0; partial remission (PR); n=6 (10%; 95%CI=3.4-18.6); stable disease (SD); n=31 (53%; 95%CI=39.0-64.4); progressive disease (PD); n=19 (33%; 95%CI=20.3-44.1). The median progression-free survival (PFS) rate (n=59) was 4.2 months (range=3.8-5.8 months). The median survival time counted from the start of second-line treatment (n=59) 14.2 months (range 8.2-17.3 months) and the median survival time counted from the start of first-line therapy (n=59) 25 months (range 19-27 months).

CONCLUSION

Palliative second-line treatment according to the AIO regimen plus irinotecan offers both a favourable toxicity profile and promising efficacy in second-line and palliative sequential therapy.

摘要

背景/目的：本研究旨在评估在一线接受奥沙利铂联合AIO方案预处理后，每周大剂量5-氟尿嘧啶（5-FU）24小时静脉滴注联合亚叶酸钙（FA）（AIO方案）加伊立替康（Iri.）进行二线治疗的疗效和安全性。

患者与方法

不可切除的远处结直肠癌转移患者参加了一项前瞻性II期研究，用于一线治疗按照AIO方案联合奥沙利铂进展后的姑息性二线治疗。患者在门诊接受治疗方案，包括每周静脉滴注1小时给予80mg/m²伊立替康，以及2000mg/m² 5-FU联合500mg/m²亚叶酸钙静脉滴注24小时，每周一次。

结果

在二线治疗期间，共有59例患者接受了520次化疗。作为主要的高级别毒性症状，8例患者（13.6%，95%CI=5.1-23.7）出现腹泻（NCI-CTC毒性3级），其次3例患者（5.1%，95%CI=0-11.9）出现白细胞减少（CTC 3级），随后1例患者（1.7%，95%CI=0-5.1）出现血小板减少（CTC 3级）。59例患者可评估治疗反应。缓解数据总结如下：完全缓解（CR）；n=0；部分缓解（PR）；n=6（10%；95%CI=3.4-18.6）；疾病稳定（SD）；n=31（53%；95%CI=39.0-64.4）；疾病进展（PD）；n=19（33%；95%CI=20.3-44.1）。中位无进展生存期（PFS）（n=59）为4.2个月（范围=3.8-5.8个月）。从二线治疗开始计算的中位生存时间（n=59）为14.2个月（范围8.2-17.3个月），从一线治疗开始计算的中位生存时间（n=59）为25个月（范围19-27个月）。