Potential of capecitabine as first-line therapy for metastatic breast cancer: dosing recommendations in patients with diminished renal function.
Potential of capecitabine as first-line therapy for metastatic breast cancer: dosing recommendations in patients with diminished renal function.
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卡培他滨作为转移性乳腺癌一线治疗的潜力：肾功能减退患者的剂量建议。
DOI：
10.1093/oxfordjournals.annonc.a000321
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发表时间：
2002
期刊：
影响因子：
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通讯作者：
J. O’Shaughnessy
中科院分区：
文献类型：
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作者：
J. O’Shaughnessy
我们最近在该杂志上报道的随机II期试验[1]表明，新型口服氟嘧啶卡培他滨在≥55岁的既往未经治疗的转移性乳腺癌女性中获得了与静脉注射CMF（环磷酰胺，甲氨蝶呤，5-氟尿嘧啶）相似的疗效。尽管该试验没有把握度能够证明疗效的显著获益，但与接受CMF的患者相比，接受卡培他滨的患者实现了更高的客观缓解率，并且有改善疾病进展时间和总生存期的趋势。卡培他滨在本研究中是可耐受的，大多数不良事件的严重程度被分级为轻度或中度。自本试验完成以来，基于对两项评价卡培他滨治疗结直肠癌患者的大型试验数据的回顾性分析，建议基线时中度肾损害患者（计算的肌酐清除率30-50 ml/min）减少卡培他滨起始剂量[2]。在我们的试验[1]中，所有患者均接受标准卡培他滨起始剂量1250 mg/m2，每日两次，持续2周，随后停药1周。然而，根据新的给药指南，这些患者中的一些（20%）现在将接受卡培他滨起始剂量（950 mg/m2，每日两次）减少25%。卡培他滨治疗组患者的中位年龄为69岁。由于计算的肌酐清除率随着年龄的增长而降低，因此可以合理预期，在接受降低卡培他滨起始剂量的老年患者中，本试验中观察到的毒性特征将得到改善。卡培他滨作为单药在蒽环类和紫杉烷类预治疗的转移性乳腺癌患者中显示出相当大的活性[3，4]。此外，最近的一项随机III期试验表明，在蒽环类药物预治疗的转移性乳腺癌患者中，多西他赛加用卡培他滨可带来显著的生存获益，使患者的中位生存期延长3个月[5]。卡培他滨已被证实的疗效和耐受性，包括脱发和骨髓抑制的发生率非常低，以及口服给药的益处，支持进一步评价卡培他滨作为转移性乳腺癌的早期治疗。为此，正在澳大利亚和新西兰进行一项随机III期试验，比较单药卡培他滨与口服经典CMF方案作为转移性乳腺癌的一线治疗。CALGB的另一项随机III期试验将比较卡培他滨与口服经典CMF或多柔比星/环磷酰胺作为65岁以上淋巴结阳性或高危淋巴结阴性乳腺癌女性的辅助治疗。在使用卡培他滨的老年乳腺癌妇女的利益强调了需要认识的年龄之间的关系，计算肌酐清除率和卡培他滨的安全性。
The randomized phase II trial that we recently reported in this journal [1] demonstrated that the novel oral fluoropyrimidine, capecitabine, achieves similar efficacy to intravenous CMF (cyclophosphamide, methotrexate, 5-fluorouracil) in women ≥55 years of age with previously untreated metastatic breast cancer. Although the trial was not powered to be able to demonstrate a significant benefit in efficacy, patients receiving capecitabine achieved a higher objective response rate with a trend towards improved time to disease progression and overall survival than patients receiving CMF. Capecitabine was tolerable in this study, with the majority of adverse events graded as mild or moderate in intensity. Since completion of this trial, a recommendation for a reduced capecitabine starting dose in patients with moderate renal impairment at baseline (calculated creatinine clearance 30–50 ml/min) has been made, based on a retrospective analysis of data from two large trials evaluating capecitabine in patients with colorectal cancer [2]. In our trial [1], all patients received the standard capecitabine starting dose of 1250 mg/m 2 twice daily for 2 weeks followed by a 1-week rest period. However, according to the new dosing guidelines, several of these patients (20%) would now receive a 25% reduction in the starting dose of capecitabine (950 mg/m 2 twice daily). The median age of patients in the capecitabinetreated group was 69 years. Since calculated creatinine clearance decreases with advanced age, it could reasonably be expected that the toxicity profile observed in this trial would be improved in elderly patients who receive a reduced starting dose of capecitabine. Capecitabine has shown considerable activity as a single agent in patients with anthracycline- and taxane-pretreated metastatic breast cancer [3, 4]. In addition, a recent, randomized, phase III trial demonstrated that the addition of capecitabine to docetaxel in patients with anthracycline-pretreated metastatic breast cancer resulted in a significant survival benefit, providing patients with a 3-month improvement in median survival [5]. The proven efficacy and tolerability of capecitabine, including the very low incidence of alopecia and myelosuppression, together with the benefits of oral administration, support further evaluation of capecitabine as early treatment for metastatic breast cancer. To this end, a randomized phase III trial is being conducted in Australia and New Zealand comparing single-agent capecitabine with the oral classical CMF regimen as first-line therapy for metastatic breast cancer. Another randomized phase III trial by the CALGB will compare capecitabine with oral classical CMF or doxorubicin/cyclophosphamide as adjuvant therapy in women >65 years old with node-positive or high-risk node-negative breast cancer. This interest in utilizing capecitabine in older women with breast cancer underscores the need for awareness of the relationship between age, calculated creatinine clearance and the safety of capecitabine.