多靶点化疗（亚叶酸钙调节的5-氟尿嘧啶推注和持续输注、奥沙利铂、伊立替康）用于晚期5-氟尿嘧啶难治性结直肠癌：最大耐受剂量的定义和疗效评估。一项I-II期研究。

Multiple-target chemotherapy (LV-modulated 5-FU bolus and continuous infusion, oxaliplatin, CPT- 11) in advanced 5-FU-refractory colorectal cancer: MTD definition and efficacy evaluation. A phase I-II study.

作者信息

Bonetti Andrea, Zaninelli Marta, Durante Emilia, Fraccon Anna Paola, Franceschi Tiziano, Pasini Felice, Zustovich Fable, Brienza Silvano

机构信息

Department of Oncology, Azienda Ospedaliera di Verona, Verona, Italy.

出版信息

Tumori. 2006 Sep-Oct;92(5):389-95.

PMID:17168430

Abstract

AIMS AND BACKGROUND

To identify the maximum tolerated doses and to define the activity of a regimen incorporating leucovorin (LV)-modulated 5-fluorouracil (5-FU) bolus and continuous infusion, oxaliplatin (I-OHP) and irinotecan (CPT-11) in patients with advanced, 5-FU-refractory colorectal cancer (CRC).

PATIENTS AND METHODS

Starting doses: LV 100 mg/m2 as a 2-hour infusion followed by 5-FU 300 mg/m2 bolus administration followed by 5-FU 500 mg/m2 as a 22-hour infusion on days 1 and 2; I-OHP 65 mg/m2 as a 2-hour infusion concomitantly with LV on day 1; CPT-11 90 mg/m2 concomitantly with LV on day 2. Planned cycle interval: 2 weeks.

RESULTS

Two hundred twenty-six cycles were administered to 27 patients. Recommended doses were 5-FU bolus 300 mg/m2, 5-FU protracted infusion 500 mg/m2, I-OHP 75 mg/m2, and CPT-11 150 mg/m2. Among 25 patients evaluable for response we observed 13 disease stabilizations (52%; 95% CI: 33-71%), 6 instances of disease progression and 6 responses (24%; 95% CI: 7-41%). Median time to progression and overall survival were 24 and 60 weeks, respectively. A cycle delay > 3 days was observed in 134/199 cycles (67%).

CONCLUSIONS

This study confirms the feasibility of triplet chemotherapy in patients with advanced 5-FU-refractory CRC.

摘要

目的与背景

确定最大耐受剂量，并明确在晚期、对5-氟尿嘧啶（5-FU）耐药的结直肠癌（CRC）患者中，包含亚叶酸（LV）调节的5-氟尿嘧啶推注及持续输注、奥沙利铂（I-OHP）和伊立替康（CPT-11）的方案的活性。

患者与方法

起始剂量：LV 100 mg/m²，静脉输注2小时，随后5-FU 300 mg/m²推注给药，接着在第1天和第2天5-FU 500 mg/m²持续静脉输注22小时；I-OHP 65 mg/m²，在第1天与LV同时静脉输注2小时；CPT-11 90 mg/m²，在第2天与LV同时使用。计划的周期间隔：2周。

结果

27例患者共接受了226个周期的治疗。推荐剂量为5-FU推注300 mg/m²、5-FU持续输注500 mg/m²、I-OHP 75 mg/m²和CPT-11 150 mg/m²。在可评估疗效的25例患者中，我们观察到13例疾病稳定（52%；95%置信区间：33%-71%）、6例疾病进展和6例缓解（24%；95%置信区间：7%-41%）。中位疾病进展时间和总生存期分别为24周和60周。在199个周期中有134个周期（67%）出现周期延迟>3天。