晚期结直肠癌患者每2周在推注5-氟尿嘧啶和大剂量亚叶酸基础上加用伊立替康或甲氨蝶呤：意大利南部肿瘤协作组的一项随机研究

Addition of either irinotecan or methotrexate to bolus 5-fluorouracil and high-dose folinic acid every 2 weeks in advanced colorectal carcinoma: a randomised study by the Southern Italy Cooperative Oncology Group.

作者信息

Comella P, Crucitta E, De Vita F, De Lucia L, Farris A, Del Gaizo F, Palmeri S, Lannelli A, Mancarella S, Tafuto S, Maiorino L, Buzzi F, De Cataldis G

机构信息

Division of Medical Oncology A, National Tumour Institute, Naples, Italy.

出版信息

Ann Oncol. 2002 Jun;13(6):866-73. doi: 10.1093/annonc/mdf133.

DOI:10.1093/annonc/mdf133

PMID:12123331

Abstract

PURPOSE

The purpose of this study was to compare the activity and toxicity of the combination of irinotecan (IRI) plus folinic acid (FA)-modulated 5-fluorouracil (5-FU) i.v. bolus with a regimen of double modulation of 5-FU with methotrexate (MTX) and FA in patients with advanced colorectal carcinoma.

PATIENTS AND METHODS

Two-hundred and thirty-four patients were enrolled: 118 patients received IRI 200 mg/m2 (90-min i.v. infusion) on day 1, followed by levo-FA 250 mg/m2 (2-h i.v. infusion) and 5-FU 850 mg/m2 (i.v. bolus) on day 2 (IRIFAFU), and 116 patients received MTX 750 mg/m2 (2-h i.v. infusion) on day 1, followed by levo-FA 250 mg/m2 (2-h i.v. infusion) and FU 800 mg/m2 (i.v. bolus) on day 2 (MTXFAFU). Both cycles were repeated every 2 weeks until progression or to a maximum of 16 cycles. Response rate (RR) was the main end point of the study; responses were assessed every four cycles and confirmed after 2 additional months of treatment.

RESULTS

RR was significantly greater with IRIFAFU (36%) than with MTXFAFU (20%) (P <0.001). Multivariate analysis showed that IRIFAFU was significantly associated with a greater activity (P = 0.028). Median progression-free survival was longer with IRIFAFU than with MTXFAFU (7.2 months compared with 4.8 months; P = 0.048). Median survival time (MST) did not differ between the two arms (14.7 months compared with 14.8 months, respectively). Patients not receiving second-line chemotherapy, however, lived longer when treated in the first-line with IRIFAFU (MST 11.9 months compared with 6.4 months; P = 0.038). IRIFAFU caused a significantly greater occurrence of grade 3 or 4 neutropenia (40% compared with 9%; P = 0.001) and diarrhoea (13% compared with 4%; P = 0.024), but a significantly lower incidence of stomatitis (3% compared with 12%; P = 0.007), than the comparative regimen.

CONCLUSIONS

IRIFAFU appeared comparable in terms of activity and toxicity with other weekly or biweekly bolus or infusional combination regimens. IRIFAFU, however, seems easier to administer, because it does not require infusional catheter or pump devices, and it is less expensive. It may represent a new option for treating advanced colorectal carcinoma.

摘要

目的

本研究旨在比较伊立替康（IRI）联合亚叶酸（FA）调节的5-氟尿嘧啶（5-FU）静脉推注方案与甲氨蝶呤（MTX）和FA双重调节5-FU方案在晚期结直肠癌患者中的活性和毒性。

患者与方法

共纳入234例患者：118例患者在第1天接受IRI 200mg/m²（90分钟静脉输注），随后在第2天接受左亚叶酸250mg/m²（2小时静脉输注）和5-FU 850mg/m²（静脉推注）（IRIFAFU方案）；116例患者在第1天接受MTX 750mg/m²（2小时静脉输注），随后在第2天接受左亚叶酸250mg/m²（2小时静脉输注）和FU 800mg/m²（静脉推注）（MTXFAFU方案）。两个周期均每2周重复一次，直至病情进展或最多进行16个周期。缓解率（RR）是本研究的主要终点；每四个周期评估一次缓解情况，并在额外治疗2个月后确认。

结果

IRIFAFU方案的RR（36%）显著高于MTXFAFU方案（20%）（P<0.001）。多因素分析显示，IRIFAFU方案与更高的活性显著相关（P = 0.028）。IRIFAFU方案的无进展生存期（PFS）中位数长于MTXFAFU方案（7.2个月对4.8个月；P = 0.048）。两组的中位生存时间（MST）无差异（分别为14.7个月和14.8个月）。然而，未接受二线化疗的患者在一线接受IRIFAFU方案治疗时生存期更长（MST为11.9个月对6.4个月；P = 0.038）。与对照方案相比，IRIFAFU方案导致3级或4级中性粒细胞减少（40%对9%；P = 0.001）和腹泻（13%对4%；P = 0.024）的发生率显著更高，但口腔炎的发生率显著更低（3%对12%；P = 0.007）。