Borner Markus M, Dietrich Daniel, Stupp Roger, Morant Rudolf, Honegger Hanspeter, Wernli Martin, Herrmann Richard, Pestalozzi Bernhard C, Saletti Piercarlo, Hanselmann Silvia, Müller Samuel, Brauchli Peter, Castiglione-Gertsch Monica, Goldhirsch Aron, Roth Arnaud D
Institute of Medical Oncology, Inselspital, Switzerland.
J Clin Oncol. 2002 Apr 1;20(7):1759-66. doi: 10.1200/JCO.2002.07.087.
To determine the efficacy and tolerability of combining oxaliplatin with capecitabine in the treatment of advanced nonpretreated and pretreated colorectal cancer.
Forty-three nonpretreated patients and 26 patients who had experienced one fluoropyrimidine-containing regimen for advanced colorectal cancer were treated with oxaliplatin 130 mg/m(2) on day 1 and capecitabine 1,250 mg/m(2) bid on days 1 to 14 every 3 weeks. Patients with good performance status (World Health Organization grade 0 to 1) were accrued onto two nonrandomized parallel arms of a phase II study.
The objective response rate was 49% (95% confidence interval [CI], 33% to 65%) for nonpretreated and 15% (95% CI, 4% to 35%) for pretreated patients. The main toxicity of this combination was diarrhea, which occurred at grade 3 or 4 in 35% of the nonpretreated and 50% of the pretreated patients. Grade 3 or 4 sensory neuropathy, including laryngopharyngeal dysesthesia, occurred in 16% of patients on both cohorts. Capecitabine dose reductions were necessary in 26% of the nonpretreated and 45% of the pretreated patients in the second treatment cycle. The median overall survival was 17.1 months and 11.5 months, respectively.
Combining capecitabine and oxaliplatin yields promising activity in advanced colorectal cancer. The main toxicity is diarrhea, which is manageable with appropriate dose reductions. On the basis of our toxicity experience, we recommend use of capecitabine in combination with oxaliplatin 130 mg/m(2) at an initial dose of 1,250 mg/m(2) bid in nonpretreated patients and at a dose of 1,000 mg/m(2) bid in pretreated patients.
确定奥沙利铂联合卡培他滨治疗晚期未经预处理及经预处理的结直肠癌的疗效和耐受性。
43例未经预处理的患者以及26例曾接受过含氟嘧啶方案治疗晚期结直肠癌的患者，每3周于第1天接受130mg/m²奥沙利铂治疗，第1至14天接受1250mg/m²卡培他滨每日2次治疗。体能状态良好（世界卫生组织0至1级）的患者纳入一项II期研究的两个非随机平行组。
未经预处理患者的客观缓解率为49%（95%置信区间[CI]，33%至65%），经预处理患者为15%（95%CI，4%至35%）。该联合治疗的主要毒性为腹泻，35%的未经预处理患者及50%的经预处理患者出现3或4级腹泻。两个队列中均有16%的患者出现3或4级感觉神经病变，包括咽喉感觉异常。在第二个治疗周期中，26%的未经预处理患者及45%的经预处理患者需要降低卡培他滨剂量。中位总生存期分别为17.1个月和11.5个月。
卡培他滨联合奥沙利铂对晚期结直肠癌具有良好疗效。主要毒性为腹泻，通过适当降低剂量可控制。基于我们的毒性经验，我们建议在未经预处理的患者中，初始剂量为卡培他滨1250mg/m²每日2次联合130mg/m²奥沙利铂，在经预处理的患者中，卡培他滨剂量为1000mg/m²每日2次。
