Santini Daniele, Vincenzi Bruno, La Cesa Annalisa, Caricato Marco, Schiavon Gaia, Spalletta Bruno, Di Seri Marisa, Coppola Roberto, Rocci Laura, Tonini Giuseppe
Medical Oncology, University Campus Bio-Medico, Rome, Italy.
Oncology. 2005;69(1):27-34. doi: 10.1159/000087285. Epub 2005 Jul 28.
The aim of the study was to define the feasibility and efficacy of Xelox (capecitabine and oxaliplatin) administered through a new and original schedule in advanced pretreated colorectal cancer (CRC) patients.
36 metastatic CRC patients resistant at least to a previous 5-fluorouracil- and irinotecan-based chemotherapy line were included in the study.
Oxaliplatin 70 mg/m2 as continuous infusion for 12 h (8.00 a.m. to 8.00 p.m.) on days 1, 8 plus chronomodulated capecitabine 1,750 mg/m2/day per os (8.00 a.m. 25% of total dose; 6.00 p.m. 25% of total dose; 11.00 p.m. 50% of total dose), on days 1-14 every 21 days. 16 (44.4%) patients had previously received only 1 chemotherapy line for metastatic disease and 20 patients (55.6%) 2 chemotherapy lines. Moreover, 12 patients (33.3%) progressed after a first or second line of oxaliplatin-based regimen as well.
Most frequent related G3-4 adverse reactions were diarrhea (11.6%), nausea/vomiting (8.3%), neuropathy (8.3%), mucositis (8.3%), asthenia (16.7%) and hand-foot syndrome (5.5%). G3-4 anemia, leucopenia and liver toxicities were not observed. The overall response rate was 30.6% (11/36 patients). Disease stabilization was observed in 13 patients (36.1%) and progression in 12 patients (34.3%). Between the 12 oxaliplatin-resistant patients, the overall response rate was 25% (3 patients); 6 patients (54.5%) obtained a stable disease, and only 3 patients (25%) progressed. The median overall survival was 11.3 months (95% confidence interval 7.0-15.7 months), the median response duration 2.8 months (95% confidence interval 1.2-5.6 months) and the median time to progression 6.7 months (95% confidence interval 5.7-6.3 months). The 1-year survival rate was 53.8%.
The high overall tumor growth control, the remarkable median time to progression and overall survival and the good safety profile are of particular interest for patients with heavy pretreated metastatic CRC.
本研究旨在确定通过一种全新且独特的给药方案给予希罗达（卡培他滨和奥沙利铂）治疗晚期经治结直肠癌（CRC）患者的可行性和疗效。
36例转移性CRC患者纳入本研究，这些患者至少对之前基于5-氟尿嘧啶和伊立替康的化疗方案耐药。
奥沙利铂70mg/m²，于第1、8天持续输注12小时（上午8点至晚上8点），同时卡培他滨按时间调节剂量1750mg/m²/天口服（上午8点服用总剂量的25%；下午6点服用总剂量的25%；晚上11点服用总剂量 的50%），每21天为1周期，第1 - 14天给药。16例（44.4%）患者之前仅接受过1线转移性疾病化疗，20例（55.6%）患者接受过2线化疗。此外，12例（33.3%）患者在一线或二线基于奥沙利铂的治疗方案后病情进展。
最常见的3 - 4级相关不良反应为腹泻（11.6%）、恶心/呕吐（8.3%）、神经病变（8.3%）、黏膜炎（8.3%）乏力（16.7%）和手足综合征（5.5%）。未观察到3 - 4级贫血、白细胞减少和肝毒性。总缓解率为30.6%（11/36例患者）。13例患者（36.1%）病情稳定，12例患者（34.3%）病情进展。在12例对奥沙利铂耐药的患者中，总缓解率为25%（3例患者）；6例患者（54.5%）病情稳定，仅3例患者（25%）病情进展。中位总生存期为11.3个月（95%置信区间7.0 - 15.7个月），中位缓解持续时间为2.8个月（95%置信区间1.2 - 5.6个月），中位疾病进展时间为6.7个月（95%置信区间5.7 - 6.3个月）。1年生存率为53.8%。
对于晚期经治转移性CRC患者而言, 高总体肿瘤生长控制率、显著的中位疾病进展时间和总生存期以及良好的安全性尤其令人关注。
