Capecitabine (Xeloda®) in combination with oxaliplatin:: a phase I, dose-escalation study in patients with advanced or metastatic solid tumors
Capecitabine (Xeloda®) in combination with oxaliplatin:: a phase I, dose-escalation study in patients with advanced or metastatic solid tumors
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DOI：
10.1093/annonc/mdf065
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发表时间：
2002-04-01
影响因子：
50.5
通讯作者：
Baselga, J
中科院分区：
文献类型：
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作者：
Díaz-Rubio, E;Evans, TRJ;Baselga, J
目的：本项I期剂量递增研究旨在确定间歇性口服卡培他滨联合固定剂量奥沙利铂静脉给药的推荐剂量。次要目标包括评估的安全性和antitumor activity.Patients和方法：23例晚期或转移性实体瘤患者接受了21天的口服卡培他滨（500，825，1000或1250 mg/m2，每日两次，第1-14天）与奥沙利铂（130 mg/m2，2小时静脉输注，第1天）联合方案。在第一个治疗周期期间确定剂量限制性毒性。结果：推荐的给药方案为口服卡培他滨1000 mg/m2，每日2次（第1-14天），静脉注射奥沙利铂130 mg/m2（第1天），21天为1个疗程。主要的剂量限制性毒性是腹泻。研究期间最常见的治疗相关不良事件为胃肠道（恶心/呕吐、腹泻）和神经系统（感觉迟钝、感觉异常）。大多数治疗相关不良事件的严重程度为轻度至中度，在接受推荐剂量或低于推荐剂量治疗的15例患者中未发生4级不良事件。最常见的3/4级实验室异常是淋巴细胞减少症（52%的患者）、血小板减少症（22%;仅3级）。中性粒细胞减少症（17%）和高胆红素血症（17%）。在患者中，以推荐剂量水平或低于推荐剂量水平治疗（n = 15）。只有两名患者经历了3级中性粒细胞减少症，没有患者经历了4级中性粒细胞减少症。6例患者（26%）发生部分肿瘤缓解，其中9例结直肠癌患者中有5例（55%）。所有有反应的患者均用5-氟尿嘧啶进行预处理，4名反应者接受了先前的irinotecan.Conclusions：口服卡培他滨静脉奥沙利铂是一种可行的联合方案，显示出有前途的抗肿瘤活性在结直肠癌患者。有一个正在进行的。II期研究，使用本研究中确定的推荐剂量，进一步表征该组合作为转移性结直肠癌一线治疗的安全性和疗效。
Objectives: This phase I, dose-escalation study was conducted to determine the recommended dose of intermittent oral capecitabine in combination with a fixed dose of i.v. oxaliplatin. Secondary objectives included evaluation of the safety profile and antitumor activity.Patients and methods: Twenty-three patients with advanced or metastatic solid tumors received a 21-day regimen of oral capecitabine (500, 825, 1000 or 1250 mg/m(2) twice daily days 1-14) in combination with oxaliplatin (130 mg/m(2), 2-h i.v. infusion, day 1). Dose-limiting toxicities were determined during the first treatment cycle. and safety and efficacy were evaluated throughout treatment.Results: The recommended dosing schedule is oral capecitabine 1000 mg/m(2) twice daily (days 1-14) with i.v. oxaliplatin 130 mg/m(2) (day 1) in a 21-day treatment cycle. The principal dose-limiting toxicity was diarrhea. The most frequent treatment-related adverse events occurring during the study were gastrointestinal (nausea/vomiting, diarrhea) and neurological (dysesthesia, paresthesia). The majority, of treatment-related adverse events were mild to moderate in intensity, and no grade 4 adverse events occur-red in the 15 patients treated at or below the recommended dose. The most common grade 3/4 laboratory abnormalities were lymphocytopenia (52% of patients), thrombocytopenia (22%; grade 3 only). neutropenia (17%) and hyperbilirubinemia (17%). Among patient., treated at or below the recommended dose level (n = 15). only two patients experienced grade 3 neutropenia and no patients experienced grade 4 neutropenia. Partial tumor responses occurred in six patients (26%), including five of nine patients (55%) with colorectal cancer. All responding patients were pretreated with 5-fluorouracil and four responders had received prior irinotecan.Conclusions: Oral capecitabine with i.v. oxaliplatin is a feasible combination regimen that shows promising antitumor activity in patients with colorectal cancer. There is an ongoing. phase II study to further characterize the safety and efficacy of this combination as first-line therapy for metastatic colorectal cancer, using the recommended dose identified in this study.