对于接受过5-氟尿嘧啶（5FU）预处理的转移性结直肠癌患者，采用甲氨蝶呤调节的大剂量5FU与亚叶酸调节的持续输注5FU的混合交替方案进行二线化疗。一项2期研究。

Second-line chemotherapy with a hybrid-alternating regimen of bolus 5FU modulated by methotrexate and infusional 5FU modulated by folinic acid in patients with metastatic colorectal cancer pretreated with 5FU. A phase 2 study.

作者信息

Carlomagno C, Lauria R, De Laurentiis M, Arpino G, Massarelli E, Ferrara C, Milano A, Vernaglia Lombardi A, Costanzo R, Catalano G, Bianco A R, De Placido S

机构信息

Division of Medical Oncology, Department of Molecular and Clinical Endocrinology and Oncology, University of Naples Federico II, Naples, Italy.

出版信息

Oncology. 2002;63(3):219-25. doi: 10.1159/000065468.

DOI:10.1159/000065468

PMID:12381900

Abstract

BACKGROUND AND AIM

In vitro, methotrexate (MTX) is the best modulator for bolus 5-fluorouracil (5FU), whereas folinic acid (FA) is the best for continuous infusion. We evaluated the effect of 5FU modulated by both MTX (bolus administration) and FA (continuous infusion) as second-line treatment of patients with metastatic colorectal cancer.

PATIENTS AND METHODS

Entry criteria were: at least one 5FU-based chemotherapy regimen as first-line treatment for metastatic disease, or progression within twelve months after 5FU-containing adjuvant therapy. Treatment schedule: MTX 200 mg/m2 i.v. days 1 and 15; 5FU 600 mg/m2 i.v. bolus, days 2 and 16; 5FU 200 mg/m2 i.v. continuous infusion for 21 days, starting on day 29; FA 20 mg/m2 i.v. bolus weekly during the three weeks of 5FU infusion. Cycles were repeated every 56 days. The primary end-point was tumour control rate, including partial responses and stabilizations.

RESULTS

34/35 patients enrolled were evaluable for response. Five (14.7%) had a partial response, 13 (38.2%) disease stabilization, and 16 (47.1%) progressed; tumour control rate was 52.9%. Median TTP was 5.8 months (95% CI 4.03-7.83); 29 patients had died. Median OAS was 15.9 months (95% CI 8.8-21.9). Toxicity was mild.

CONCLUSIONS

The regimen constituted by 5FU modulated by MTX (bolus administration) and FA (continuous infusion) is active as second-line treatment of metastatic colorectal cancer.

摘要

背景与目的

在体外实验中，甲氨蝶呤（MTX）是大剂量5-氟尿嘧啶（5FU）的最佳调节剂，而亚叶酸（FA）则是持续输注5FU的最佳调节剂。我们评估了由MTX（大剂量给药）和FA（持续输注）调节的5FU作为转移性结直肠癌患者二线治疗的效果。

患者与方法

入选标准为：至少接受过一种以5FU为基础的化疗方案作为转移性疾病的一线治疗，或在含5FU的辅助治疗后12个月内病情进展。治疗方案：MTX 200 mg/m²静脉注射，第1天和第15天；5FU 600 mg/m²静脉推注，第2天和第16天；5FU 200 mg/m²静脉持续输注21天，从第29天开始；FA 20 mg/m²静脉推注，在5FU输注的三周内每周一次。每56天重复一个周期。主要终点是肿瘤控制率，包括部分缓解和病情稳定。

结果

35例入选患者中有34例可评估疗效。5例（14.7%）部分缓解，13例（38.2%）病情稳定，16例（47.1%）病情进展；肿瘤控制率为52.9%。中位无进展生存期为5.8个月（95%CI 4.03 - 7.83）；29例患者死亡。中位总生存期为15.9个月（95%CI 8.8 - 21.9）。毒性较轻。