奥沙利铂联合卡培他滨（XELOX）时辰调制给药作为晚期结直肠癌患者一线化疗的II期研究

Chronomodulated administration of oxaliplatin plus capecitabine (XELOX) as first line chemotherapy in advanced colorectal cancer patients: phase II study.

作者信息

Santini Daniele, Vincenzi Bruno, Schiavon Gaia, Di Seri Marisa, Virzí Vladimir, Spalletta Bruno, Caricato Marco, Coppola Roberto, Tonini Giuseppe

机构信息

Medical Oncology, University Campus Bio-Medico, Via Emilio Longoni, 69, 00155 Rome, Italy.

出版信息

Cancer Chemother Pharmacol. 2007 Apr;59(5):613-20. doi: 10.1007/s00280-006-0302-x. Epub 2006 Aug 31.

DOI:10.1007/s00280-006-0302-x

PMID:16944151

Abstract

BACKGROUND

The combination of 5-fluorouracil (5-FU), leucovorin (LV), and oxaliplatin (I-OHP) was shown to be both more active against metastatic colorectal carcinoma and better tolerated if the drug delivery rate was chronomodulated according to circadian rhythms rather than constant. The aim of the present study was to define the feasibility and efficacy of XELOX administered through a new chronomodulated schedule in untreated advanced colorectal cancer (CRC) patients.

METHODS

Chemotherapy-naive patients with advanced CRC were considered eligible for the study accrual.

TREATMENT

oxaliplatin 70 mg/m(2) continuous infusion (c.i.) for 12 h (8:00 a.m. to 8:00 p.m.) days 1, 8 plus chronomodulated oral capecitabine 1,750 mg/m(2)/die (h 8:00 a.m. 25% of total dose; h 6:00 p.m. 25% of total dose; h 11:00 p.m. 50% of total dose), days 1-14 every 21 days.

RESULTS

Forty-six patients were evaluated for safety and efficacy (male/female, 20/26). Median age was 64 years (range 28-77 years). Median Eastern Cooperative Oncology Group performance status (PS) was 0 (range 0-1). A total of 324 cycles have been administered: median per patient 6 (range 3-10 courses). Median number of metastatic sites was 1. Metastatic sites distribution was as follows: liver (65.2%), lung (34.8%), and nodes (32.6%). Median follow-up was 14 months (range 6.0-40.3 months). In an intent-to-treat efficacy analysis, objective response and stable disease were recorded in 27 (58.6%) and in 16 patients (34.9%), respectively. The median response duration was 8.0 months (95% CI; 5.03-10.96 months). The median time to progression (TTP) was 9.0 months (95% CI; 6.47-11.52 months). The overall survival (OS) was not reached, with a median value > 24 months (95% CI; 23.66-36.30 months). The grade 3 toxicities were diarrhea (8.7%), liver toxicity (13.1%), fatigue (8.7%), neurotoxicity (2.2%), neutropenia (8.7%), and thrombocytopenia (2.2%).

CONCLUSION

This regimen resulted of particular interest for patients with untreated metastatic CRC.

摘要

背景

研究表明，对于转移性结直肠癌，与持续给药相比，将5-氟尿嘧啶（5-FU）、亚叶酸钙（LV）和奥沙利铂（L-OHP）按昼夜节律进行时辰调节给药，不仅活性更高，耐受性也更好。本研究旨在确定在未经治疗的晚期结直肠癌（CRC）患者中，通过新的时辰调节方案给予XELOX方案的可行性和疗效。

方法

未接受过化疗的晚期CRC患者被认为符合本研究入组条件。

治疗

奥沙利铂70mg/m²持续输注（c.i.）12小时（上午8:00至晚上8:00），第1、8天给药，加时辰调节口服卡培他滨1750mg/m²/天（上午8:00给药总量的25%；下午6:00给药总量的25%；晚上11:00给药总量的50%），第1 - 14天给药，每21天为一周期。

结果

46例患者接受了安全性和疗效评估（男性/女性，20/26）。中位年龄为64岁（范围28 - 77岁）。东部肿瘤协作组（Eastern Cooperative Oncology Group）中位体能状态（PS）为0（范围0 - 1）。共进行了324个周期的治疗：每位患者中位治疗周期数为6个（范围3 - 10个疗程）。转移部位中位数为1个。转移部位分布如下：肝脏（65.2%）、肺（34.8%）和淋巴结（32.6%）。中位随访时间为14个月（范围6.0 - 40.3个月）。在意向性疗效分析中，分别有27例（58.6%）患者出现客观缓解，16例（34.9%）患者病情稳定。中位缓解持续时间为8.0个月（95%CI；5.03 - 10.96个月）。中位疾病进展时间（TTP）为9.0个月（95%CI；6.47 - 11.52个月）。总生存期（OS）未达到，中位值>24个月（95%CI；23.66 - 36.30个月）。3级毒性反应包括腹泻（8.7%）、肝毒性（13.1%）、疲劳（8.7%）、神经毒性（2.2%）、中性粒细胞减少（8.7%）和血小板减少（2.2%）。