在结直肠癌（CRC）中，采用AIO方案预处理后，进行每周一次的高剂量5-氟尿嘧啶24小时输注联合亚叶酸钙（AIO）加奥沙利铂的姑息性二线治疗。

Palliative second-line treatment with weekly high-dose 5-fluorouracil as 24-hour infusion and folinic acid (AIO) plus oxaliplatin after pre-treatment with the AIO-regimen in colorectal cancer (CRC).

作者信息

Link K, Happich K, Schirner I, Jüngert B, Brückl V, Männlein G, Brückl W M, Merkel S, Göhl J, Hohenberger W, Hahn E G, Wein A

机构信息

Department of Internal Medicine I, University of Erlangen, Germany.

出版信息

Anticancer Res. 2004 Jan-Feb;24(1):385-91.

PMID:15015625

Abstract

BACKGROUND AND AIMS

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.) and folinic acid (FA) (AIO-regimen) plus Oxaliplatin (L-OHP) after pre-treatment with the AIO regimen, focusing in particular on the efficacy of palliative first- and second-line treatment in colorectal carcinoma (CRC).

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 palliative first-line treatment in accordance with the AIO regimen. On an outpatient basis, the patients received a treatment regimen comprising biweekly 85 mg/m2 L-OHP in the form of a 2-hour intravenous (i.v.) infusion and 500 mg/m2 FA as a 1 to 2-hour i.v. infusion, followed by 2,600 mg/m2 5-FU administered as a 24-h inf. i.v. once weekly. A single treatment cycle comprised 6 weekly infusions followed by 2 weeks of rest.

RESULTS

During second-line treatment, a total of 26 patients received 340 chemotherapy applications. As the main symptom of toxicity, diarrhoea (NCI-CTC toxicity grade 3+4) presented in 5 patients (19%; 95% CI: 4-34), followed by nausea (CTC grade 3) in one patient (4%; 95% CI: 0-11). Twenty-three patients were evaluable for treatment response. The remission data can be summarised as follows: Complete remission (CR): n=1 (4%; 95% CI: 0-13); partial remission (PR): n=3 (13%; 95% CI: 0-27); stable disease (SD): n=11 (48%; 95% CI: 27-68) and progressive disease (PD): n=8 (35%; 95% CI: 15-54). The median progression-free survival (PFS) rate (n=26) was 3.3 months (range 0-11.5), the median survival time counted from the start of second-line treatment (n=26) 11.6 months (range 2.1-33.0) and the median survival time counted from the start of first-line treatment (n=26) 19.9 months (range 7.7-49.8).

CONCLUSION

Palliative second-line treatment according to the AIO regimen plus L-OHP is feasible in an outpatient setting and well tolerated by the patients. Tumour control (CR + PR + SD) was achieved in 65% of the patients, the median survival time being 11.6 months. The AIO regimen followed by the 'AIO regimen plus L-OHP' therapy sequence led to a promising median survival time of 19.9 months (range 7.7-49.8).

摘要

背景与目的

本研究旨在评估在接受AIO方案预处理后，采用每周大剂量5-氟尿嘧啶（5-FU）持续24小时静脉输注（24-h inf.）联合亚叶酸（FA）（AIO方案）加奥沙利铂（L-OHP）进行二线治疗的疗效和安全性，尤其关注结直肠癌（CRC）姑息性一线和二线治疗的疗效。

患者与方法

不可切除的远处CRC转移患者参加了一项前瞻性II期研究，该研究针对先前按照AIO方案进行姑息性一线治疗后的姑息性二线治疗。患者在门诊接受治疗方案，包括每两周一次85mg/m²的L-OHP，静脉输注2小时，以及500mg/m²的FA，静脉输注1至2小时，随后每周一次静脉输注24小时给予2600mg/m²的5-FU。一个治疗周期包括6次每周输注，随后休息2周。

结果

在二线治疗期间，共有26例患者接受了340次化疗。作为主要毒性症状出现腹泻（NCI-CTC毒性3 + 4级）的患者有5例（19%；95%CI：4 - 34），其次是1例出现恶心（CTC 3级）的患者（4%；95%CI：0 - 11）。23例患者可评估治疗反应。缓解数据总结如下：完全缓解（CR）：n = 1（4%；95%CI：0 - 13）；部分缓解（PR）：n = 3（13%；95%CI：0 - 27）；疾病稳定（SD）：n = 11（48%；95%CI：27 - 68）；疾病进展（PD）：n = 8（35%；95%CI：15 - 54）。无进展生存期（PFS）的中位数（n = 26）为3.3个月（范围0 - 11.5），从二线治疗开始计算的中位生存时间（n = 26）为11.6个月（范围2.1 - 33.0），从一线治疗开始计算的中位生存时间（n = 26）为19.9个月（范围7.7 - 49.8）。