Impact of Chemotherapy Dose Intensity on Cancer Patient Outcomes
Impact of Chemotherapy Dose Intensity on Cancer Patient Outcomes
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DOI：
10.6004/jnccn.2009.0009
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发表时间：
2009-01-01
影响因子：
13.4
通讯作者：
Lyman, Gary H.
中科院分区：
文献类型：
--
作者：
Lyman, Gary H.
化疗剂量强度代表每单位时间施用的化疗的单位剂量。可以通过改变施用剂量、施用时间间隔或两者来增加或减少剂量强度。支持化疗剂量强度对潜在可治愈恶性肿瘤患者临床结果重要性的证据来自癌细胞系的体外研究和大量的体内临床前研究，以及晚期和早期疾病环境中的回顾性和前瞻性临床试验。骨髓抑制仍然是癌症化疗的主要剂量限制性毒性，导致相当大的发病率和死亡率，同时频繁降低化疗剂量强度，这可能会损害疾病控制和生存。几项回顾性和前瞻性随机试验表明，疗效研究中确定的化疗剂量强度的降低可能会损害长期疾病控制和生存。尽管有令人信服的数据，但美国和其他地方的调查报告称，临床实践中经常发生剂量减少和延迟，甚至在潜在的治疗环境中也是如此。或者，可以通过增加单个药物的剂量（剂量递增）或压缩或缩短治疗间隔（剂量密集）来实现高于标准的剂量强度增加。在早期研究中，剂量密集方案显示生存率增加，而剂量递增研究的益处不太一致，并且可能伴有其他剂量限制性毒性。本文重点介绍提供全化疗剂量强度的基本原理、未能提供最佳治疗的明显原因以及在需要时维持全化疗剂量强度的可用策略。对患有潜在可治愈恶性肿瘤的患者提供完整的化疗剂量强度应被视为临床肿瘤学的护理质量指标。 (JNCCN 2009;7:99-108)
Chemotherapy dose intensity represents unit dose of chemotherapy administered per unit time. Dose intensity can be increased or decreased through altering dose administered, time interval of administration, or both. Evidence supporting the importance of delivered chemotherapy dose intensity on clinical outcomes in patients with potentially curable malignancies comes from in vitro studies of cancer cell lines and abundant in vivo preclinical studies, in addition to retrospective and prospective clinical trials in both advanced and early-stage disease settings. Myelosuppression continues to represent the major dose-limiting toxicity of cancer chemotherapy, resulting in considerable morbidity and mortality along with frequent reductions in chemotherapy dose intensity, which may compromise disease control and survival. Several retrospective and prospective randomized trials have shown that reductions in the chemotherapy dose intensity established in efficacy studies may compromise long-term disease control and survival. Despite compelling data, surveys in the United States and elsewhere have reported that dose reductions and delays frequently occur in clinical practice, even in the potentially curative setting. Alternatively, an increase in dose intensity above standard may be achieved through either increasing the dose of individual agents (dose escalation) or compressing or shortening the treatment interval (dose-dense). In early studies, dose-dense schedules showed an increase in survival, whereas the benefit of dose escalation studies has been less consistent and may be accompanied by other dose-limiting toxicities. This article focuses on the rationale for delivering full chemotherapy dose intensity, the apparent reasons for failing to deliver optimal treatment, and available strategies for sustaining full chemotherapy dose intensity when indicated. The delivery of full chemotherapy dose intensity in patients with potentially curable malignancies should be considered a quality of care indicator in clinical oncology. (JNCCN 2009;7:99-108)