Shields Anthony F, Zalupski Mark M, Marshall John L, Meropol Neal J
Department of Medicine, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan 48201, USA.
Cancer. 2004 Feb 1;100(3):531-7. doi: 10.1002/cncr.11925.
The current study was designed to evaluate the antitumor activity and toxicity of capecitabine and oxaliplatin in previously untreated patients with advanced colorectal carcinoma. The primary endpoint of the study was to determine the objective response rate, and a secondary endpoint was to measure the time to disease progression.
A 2-stage trial was planned with an accrual goal of 35 patients. The treatment included oxaliplatin given at a dose of 130 mg/m2 on Day 1 of each 3-week cycle. Initially, capecitabine at a dose of 2000 mg/m2/day in 2 divided doses was given on Days 1-14 of each cycle, but this was reduced to a dose of 1500 mg/m2/day because of toxicity. Patients were followed by computed tomography scans every two cycles to evaluate treatment response, and toxicity was monitored.
The first 13 patients on the trial received the higher dose of capecitabine. Although 5 responses (38.5%) were noted, 5 patients were hospitalized with diarrhea and dehydration. This toxicity led to a decrease in the dose of capecitabine to 1500 mg/m2/day and an additional 35 patients were treated. At the lower dose, the partial response rate was 37.1% (95% confidence interval [95% CI], 21.5-55.1%). The estimated median progression-free survival was 6.9 months (95% CI, 4.4-8.2 months). At the lower dose, four patients were hospitalized with diarrhea/dehydration (with one death reported), one with febrile neutropenia, and one with ventricular fibrillation. Overall, Grade (according to version 2.0 of the National Cancer Institute Common Toxicity Criteria) 3-4 diarrhea was reported to develop in 20% of those patients treated at the capecitabine dose of 1500 mg/m2/day compared with 62% of patients treated at the dose of 2000 mg/m2/day.
The combination of oxaliplatin and capecitabine is an active and convenient regimen for the treatment of patients with advanced colorectal carcinoma and should be compared with other front-line regimens as therapy for disease.
本研究旨在评估卡培他滨和奥沙利铂对既往未接受过治疗的晚期结直肠癌患者的抗肿瘤活性及毒性。本研究的主要终点是确定客观缓解率，次要终点是测量疾病进展时间。
计划进行一项两阶段试验，目标入组35例患者。治疗方案包括每3周为一个周期，在第1天给予奥沙利铂，剂量为130mg/m²。最初，卡培他滨剂量为2000mg/m²/天，分2次给药，在每个周期的第1 - 14天使用，但由于毒性反应，剂量减至1500mg/m²/天。每两个周期对患者进行计算机断层扫描以评估治疗反应，并监测毒性反应。
试验中的前13例患者接受了较高剂量的卡培他滨。尽管观察到5例缓解（38.5%），但有5例患者因腹泻和脱水住院。这种毒性反应导致卡培他滨剂量减至1500mg/m²/天，并对另外35例患者进行了治疗。在较低剂量时，部分缓解率为37.1%（95%置信区间[95%CI]，21.5 - 55.1%）。估计的无进展生存期中位数为6.9个月（95%CI，4.4 - 8.2个月）。在较低剂量时，有4例患者因腹泻/脱水住院（报告1例死亡），1例因发热性中性粒细胞减少症住院，1例因室颤住院。总体而言，按照美国国立癌症研究所通用毒性标准第2.0版，接受1500mg/m²/天卡培他滨剂量治疗的患者中，20%出现3 - 4级腹泻，而接受2000mg/m²/天剂量治疗的患者中这一比例为62%。
奥沙利铂与卡培他滨联合方案是治疗晚期结直肠癌患者的一种有效且便捷的方案，应与其他一线方案进行比较作为疾病的治疗方法。
