Randomized multicenter phase II trial of two different schedules of capecitabine plus oxaliplatin as first-line treatment in advanced colorectal cancer
Randomized multicenter phase II trial of two different schedules of capecitabine plus oxaliplatin as first-line treatment in advanced colorectal cancer
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DOI：
10.1200/jco.2003.09.016
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发表时间：
2003-04-01
影响因子：
45.3
通讯作者：
Depisch, D
中科院分区：
文献类型：
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作者：
Scheithauer, W;Kornek, GV;Depisch, D
目的：卡培他滨和奥沙利铂是两种具有潜在协同活性的新药，已在晚期结直肠癌（ACC）中显示出有希望的抗肿瘤疗效。临床前和临床证据表明，口服氟尿嘧啶前药的剂量强化可能导致改善的治疗结果，导致我们进行本随机多中心II期研究。89例患有二维可测量ACC且先前未接受转移性疾病治疗的患者被随机分配接受奥沙利铂130 mg/m2第1天加卡培他滨2，000 mg/m2/d，第1 - 14天，每3周一次（A组）或接受奥沙利铂85 mg/m2，第1天和第14天联合卡培他滨3，500 mg/m2，第1 - 7天和第14 - 21天，每4周一次（B组）。在两个治疗组中，除非有先前的疾病进展证据，否则化疗总共持续6个月。结果：分配到高剂量卡培他滨联合治疗组B的患者具有更高的放射学证实的应答率（54.5% v42.2%）和中位无进展生存期显著长于对照组A（10.5 v6.0个月; P = 0.0013）。此时无法计算任一治疗组的中位总生存时间。尽管B组卡培他滨的剂量强度高34%，但治疗组之间的血液学毒性无差异（中性粒细胞减少/血小板减少：B组60%/43% vs A组56%/33%）。同样，非血液学不良事件的发生率和程度也相当：（所有等级，A组和B组）包括恶心/呕吐（A：58%; B：62%），腹泻（A：44%; B：31%），周围感觉神经病变（A：80%; B：83%）和疲劳结论：两种联合方案均可行，耐受性好，临床疗效显著。然而，剂量强化的每两个月一次卡培他滨组似乎在增加缓解率和无进展生存时间方面更有效。(C)2003年，美国临床肿瘤学会。
Purpose: Capecitabine and oxaliplatin, two new agents with potential synergistic activity, have demonstrated promising antitumor efficacy in advanced colorectal cancer (ACC). Preclinical and clinical evidence indicating that dose intensification of the oral fluorouracil prodrug might result in improved therapeutic results led us to the present randomized multicenter phase II study.Patients and Methods: Eighty-nine patients with bidimensionally measurable ACC previously untreated for metastatic disease were randomly allocated to receive oxaliplatin 130 mg/m(2) day 1 plus capecitabine 2,000 mg/m(2)/d days 1 to 14 every 3 weeks (arm A) or to receive oxaliplatin 85 mg/m(2) days 1 and 14 combined with capecitabine 3,500 mg/m(2) days 1 to 7 and 14 to 21 every 4 weeks (arm B). In both treatment arms, chemotherapy was continued for a total of 6 months unless there was prior evidence of progression of disease.Results: Patients allocated to the high-dose capecitabine combination arm B had a higher radiologically confirmed response rate (54.5% v 42.2%) and a significantly longer median progression-free survival time than those allocated to control arm A (10.5 v 6.0 months; P = .0013). Median overall survival times cannot be calculated for either treatment arm at this point. Despite a 34% higher dose intensity of capecitabine in arm B, there was no difference in hematologic toxicity between treatment arms (neutropenia/thrombocytopenia: 60%/43% in arm B v 56%/33% in arm A). Similarly, the incidence rate and degree of nonhematologic adverse events were comparable: The most commonly encountered symptoms (all grades, arm A and arm B) included nausea/emesis (A: 58%; B: 62%), diarrhea (A: 44%; B: 31%), peripheral sensory neuropathy (A: 80%; B: 83%), and fatigue (A: 40%; B: 50%).Conclusion: Results of this study indicate that both combination regimens are feasible, tolerable, and clinically active. The dose-intensified bimonthly capecitabine arm, however, seems to be more effective in increasing both response rate and progression-free survival time. (C) 2003 by American Society of Clinical Oncology.