Citron Marc L
Albert Einstein College of Medicine, Bronx, New York, USA.
Cancer Invest. 2004;22(4):555-68. doi: 10.1081/cnv-200027134.
Dose-dense chemotherapy increases the dose intensity of the regimen by delivering standard-dose chemotherapy with shorter intervals between the cycles. This article discusses the rationale for dose-dense therapy and reviews the results with dose-dense adjuvant regimens in recent clinical trials in breast cancer.
The papers for this review covered evidence of a dose-response relation in cancer chemotherapy; the rationale for dose-intense (and specifically dose-dense) therapy; and clinical experience with dose-dense regimens in adjuvant chemotherapy for breast cancer, with particular attention to outcomes and toxicity.
Evidence supports maintaining the dose intensity of adjuvant chemotherapy within the conventional dose range. Disease-free and overall survival with combination cyclophosphamide, methotrexate, and fluorouracil are significantly improved when patients receive within 85% of the planned dose. Moderate and high dose cyclophosphamide, doxorubicin, and fluorouracil within the standard range results in greater disease-free and overall survival than the low dose regimen. The sequential addition of paclitaxel after concurrent doxorubicin and cyclophosphamide also significantly improves survival. Disease-free and overall survival with dose-dense sequential or concurrent doxorubicin, cyclophosphamide, and paclitaxel with filgrastim (rhG-CSF; NEUPOGEN) support are significantly greater than with conventional schedules (q21d).
The delivered dose intensity of adjuvant chemotherapy within the standard dose range is an important predictor of the clinical outcome. Prospective trials of high-dose chemotherapy have shown no improvement over standard regimens, and toxicity was greater. Dose-dense adjuvant chemotherapy improves the clinical outcomes with doxorubicin-containing regimens. Filgrastim support enables the delivery of dose-dense chemotherapy and reduces the risk of neutropenia and its complications.
剂量密集化疗通过缩短化疗周期之间的间隔给予标准剂量化疗，从而提高方案的剂量强度。本文讨论了剂量密集治疗的基本原理，并回顾了近期乳腺癌临床试验中剂量密集辅助方案的结果。
本综述的论文涵盖了癌症化疗中剂量反应关系的证据；剂量密集（特别是剂量密集）治疗的基本原理；以及乳腺癌辅助化疗中剂量密集方案的临床经验，特别关注疗效和毒性。
有证据支持在常规剂量范围内维持辅助化疗的剂量强度。当患者接受计划剂量的85%以内时，环磷酰胺、甲氨蝶呤和氟尿嘧啶联合使用的无病生存期和总生存期显著改善。标准范围内的中高剂量环磷酰胺、多柔比星和氟尿嘧啶比低剂量方案能带来更长的无病生存期和总生存期。在多柔比星和环磷酰胺同时使用后序贯添加紫杉醇也显著提高了生存率。剂量密集序贯或同时使用多柔比星、环磷酰胺和紫杉醇并给予非格司亭（重组人粒细胞集落刺激因子；惠尔血）支持的无病生存期和总生存期显著长于传统方案（每21天一次）。
标准剂量范围内辅助化疗的给药剂量强度是临床结果的重要预测指标。高剂量化疗的前瞻性试验显示，与标准方案相比并无改善，且毒性更大。剂量密集辅助化疗可改善含多柔比星方案的临床结果。非格司亭支持能够实施剂量密集化疗，并降低中性粒细胞减少及其并发症的风险。
