雷替曲塞与丝裂霉素-C作为包括5-氟尿嘧啶、伊立替康和奥沙利铂的联合方案后结直肠癌三线化疗的II期研究。

Raltitrexed and mitomycin-C as third-line chemotherapy for colorectal cancer after combination regimens including 5-fluorouracil, irinotecan and oxaliplatin: a phase II study.

作者信息

Rosati Gerardo, Rossi Antonio, Germano Domenico, Reggiardo Giorgio, Manzione Luigi

机构信息

Medical Oncology Unit, S. Carlo Hospital, Potenza, Italy.

出版信息

Anticancer Res. 2003 May-Jun;23(3C):2981-5.

PMID:12926149

Abstract

BACKGROUND

To investigate the therapeutic value and safety of a third-line treatment with raltitrexed and mitomycin-C (MMC) in patients with advanced colorectal cancer (ACC) pretreated with combination regimens including 5-fluorouracil (5-FU), irinotecan (CPT-11) and oxaliplatin (L-OHP).

PATIENTS AND METHODS

A total of 21 patients (PS 1/2, 19/2; M/F 15/6; median age = 73) with ACC, all of whom had developed progressive disease while receiving or within 6 months of discontinuing two sequential chemotherapy lines with 5-FU, CPT-11 and L-OHP, were accrued in this study. At the time of their relapse, cytotoxic chemotherapy, consisting of intravenous raltitrexed 3 mg/m2 plus MMC 6 mg/m2 on therapeutic day 1, was initiated. Treatment courses were repeated every 4 weeks for a total of six courses unless there was prior evidence of progressive disease, unacceptable toxicity or patient refusal occurred.

RESULTS

All the patients were assessable for toxicity and 16 for response evaluation, having completed at least two courses of chemotherapy. The overall response rate was 0%. Seven patients (33.6%) had a stable disease and nine patients (43%) progressed. The median time to progression was 2.3 months (95% CI: 1.65-2.95%) and median overall survival (OS) 5 months (95% CI: 2.52-7.48%). No toxic deaths occurred. Third-line treatment tolerance was generally mild to moderate and easy to treat. WHO grade 3/4 anemia, neutro- and thrombocytopenia occurred in 9.5%, 4.7% and 4.7% of the patients, respectively. However, these toxicities did not have a significant impact on global quality of life.

CONCLUSION

Our data suggest that the association of raltitrexed and MMC in patients with ACC pretreated with combination regimens including 5-FU, CPT-11 and L-OHP is feasible and could contribute to increase patients' OS time. Further evaluation of this regimen seems to be warranted.

摘要

背景

探讨雷替曲塞与丝裂霉素-C（MMC）联合进行三线治疗在接受过包括5-氟尿嘧啶（5-FU）、伊立替康（CPT-11）和奥沙利铂（L-OHP）的联合方案预处理的晚期结直肠癌（ACC）患者中的治疗价值和安全性。

患者与方法

本研究纳入了21例ACC患者（体能状态1/2，19/2；男/女15/6；中位年龄 = 73岁），所有患者在接受含5-FU、CPT-11和L-OHP的两线序贯化疗期间或停药后6个月内出现疾病进展。在复发时，开始进行细胞毒性化疗，于治疗第1天静脉给予雷替曲塞3 mg/m²加MMC 6 mg/m²。除非有疾病进展、不可接受的毒性或患者拒绝治疗的先前证据，治疗疗程每4周重复一次，共六个疗程。

结果

所有患者均可评估毒性，16例可评估疗效，均完成了至少两个疗程的化疗。总缓解率为0%。7例患者（33.6%）病情稳定，9例患者（43%）病情进展。中位疾病进展时间为2.3个月（95%置信区间：1.65 - 2.95%），中位总生存期（OS）为5个月（95%置信区间：2.52 - 7.48%）。未发生毒性死亡。三线治疗耐受性一般为轻至中度，易于处理。WHO 3/4级贫血、中性粒细胞减少和血小板减少分别发生在9.5%、4.7%和4.7%的患者中。然而，这些毒性对整体生活质量没有显著影响。