Division of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Canada.
Eur J Cancer. 2013 Nov;49(16):3387-95. doi: 10.1016/j.ejca.2013.06.038. Epub 2013 Jul 20.
Low-dose metronomic (LDM) chemotherapy, the frequent and continuous use of low doses of conventional chemotherapeutics, is an emerging alternative to conventional chemotherapy. While promising tumour control rates and excellent safety profiles have been observed, there are no definitive phase III trial results. Furthermore, the selection of patients, drug dosages and dosing intervals is empirical. To systematically review the current state of knowledge regarding LDM chemotherapy, we searched the MEDLINE, EMBASE, CENTRAL and PubMed databases for fully published LDM chemotherapy trials. We calculated the relative dose-intensity (RDI, mg/m(2)/week) of each LDM regimen as compared to conventional maximum tolerated dose (MTD) dosages and the 'dosing-density' (DD, % of days with chemotherapy administration per cycle). Meta-regression was performed to examine factors associated with disease control rate (DCR; complete response (CR)+partial response (PR)+stable disease (SD)). Eighty studies involving mainly pretreated patients with advanced/metastatic breast (26.25%) and prostate (11.25%) cancers were retrieved. The most commonly used drug was cyclophosphamide (43%). LDM chemotherapy was frequently combined with other therapies (64.5%). Response rate (RR) and progression-free survival (PFS) were the most frequent primary end-points (24% and 19%). Mean RR was 26.03% (95% confidence interval (CI): 21.4-30.7), median PFS was 4.6months (interquartile range (IQR): 2.9-7.0) and mean DCR was 56.3% (95% CI: 50.9-61.6). RDI, DD and metronomic drug used were not associated with DCR. Grade 3/4 adverse events were rare (anaemia 7.78%, fatigue 13.4%). Thus, LDM therapy appears to be clinically beneficial and safe in a broad range of tumors. However, meta-regression analysis did not identify predictive factors of response.
低剂量节拍化疗（LDM）是一种新兴的常规化疗替代方案，它是指频繁和连续使用低剂量常规化疗药物。虽然观察到了有希望的肿瘤控制率和极好的安全性特征，但尚无明确的 III 期试验结果。此外，患者选择、药物剂量和给药间隔都是经验性的。为了系统地回顾 LDM 化疗的现有知识状态，我们在 MEDLINE、EMBASE、CENTRAL 和 PubMed 数据库中搜索了已发表的 LDM 化疗试验。我们计算了每个 LDM 方案的相对剂量强度（RDI，mg/m2/周）与常规最大耐受剂量（MTD）剂量相比，以及“给药密度”（DD，每个周期接受化疗的天数百分比）。进行了荟萃回归分析，以研究与疾病控制率（DCR；完全缓解（CR）+部分缓解（PR）+稳定疾病（SD））相关的因素。共检索到 80 项主要涉及晚期/转移性乳腺癌（26.25%）和前列腺癌（11.25%）的预处理患者的研究。最常用的药物是环磷酰胺（43%）。LDM 化疗经常与其他疗法联合使用（64.5%）。应答率（RR）和无进展生存期（PFS）是最常见的主要终点（24%和 19%）。平均 RR 为 26.03%（95%置信区间（CI）：21.4-30.7），中位 PFS 为 4.6 个月（四分位距（IQR）：2.9-7.0），平均 DCR 为 56.3%（95%CI：50.9-61.6）。RDI、DD 和使用的节拍药物与 DCR 无关。3/4 级不良事件罕见（贫血 7.78%，疲劳 13.4%）。因此，LDM 治疗在广泛的肿瘤中似乎具有临床益处和安全性。然而，荟萃回归分析未确定反应的预测因素。
