Puhalla Shannon, Mrozek Ewa, Young Donn, Ottman Susan, McVey Anne, Kendra Kari, Merriman Nancy J, Knapp Mark, Patel Taral, Thompson Mark E, Maher James F, Moore Timothy D, Shapiro Charles L
Ohio State University, Columbus, OH 43210, USA.
J Clin Oncol. 2008 Apr 1;26(10):1691-7. doi: 10.1200/JCO.2007.14.3941. Epub 2008 Mar 3.
An anthracycline-based combination followed by, or combined with, a taxane is the sequence used in most adjuvant chemotherapy regimens. We hypothesized that administering the taxane before the anthracycline combination would be associated with fewer dose reductions and delays than the reverse sequence. To test this hypothesis, a randomized phase II multicenter adjuvant chemotherapy trial was performed.
Fifty-six patients with axillary node-positive, nonmetastatic breast cancer were randomly assigned either to group A (docetaxel [DOC] 75 mg/m(2) intravenously [IV] every 14 days for four cycles followed by doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) [AC] IV every 14 days for four cycles); or to group B (AC followed by DOC) at the identical doses and schedule. Pegfilgrastim 6 mg subcutaneous injection was administered 1 day after the chemotherapy in all treatment cycles. The primary objective was to administer DOC without dose reductions or delays before or after AC and calculate the relative dose intensity (RDI) of DOC and AC.
The majority of toxicities were grade 0 to 2 irrespective of sequence. The RDI for DOC was 0.96 and 0.82, respectively, in groups A (DOC followed by AC) and B (AC followed by DOC), with more frequent dose reductions occurring in group B (46% v 18%). The RDI for AC was 0.95 and 0.98 in groups A and B, respectively.
The administration of DOC before AC results in fewer DOC dose reductions and a higher RDI than the reverse sequence. Larger trials evaluating the sequence of DOC before anthracyclines are justified.
大多数辅助化疗方案采用的顺序是先进行基于蒽环类药物的联合化疗，随后或联合紫杉烷类药物。我们假设，与相反顺序相比，在蒽环类药物联合化疗之前给予紫杉烷类药物会减少剂量降低和延迟的情况。为了验证这一假设，我们开展了一项随机II期多中心辅助化疗试验。
56例腋窝淋巴结阳性、非转移性乳腺癌患者被随机分为A组（多西他赛[DOC]75mg/m²静脉注射[IV]，每14天1次，共4个周期，随后给予多柔比星60mg/m²和环磷酰胺600mg/m²[AC]静脉注射，每14天1次，共4个周期）；或B组（AC序贯DOC），剂量和疗程相同。在所有治疗周期的化疗后1天给予聚乙二醇化重组人粒细胞刺激因子6mg皮下注射。主要目的是在AC之前或之后给予DOC时不进行剂量降低或延迟，并计算DOC和AC的相对剂量强度（RDI）。
无论顺序如何，大多数毒性反应为0至2级。A组（DOC序贯AC）和B组（AC序贯DOC）中DOC的RDI分别为0.96和0.82，B组剂量降低更为频繁（46%对18%）。A组和B组中AC的RDI分别为0.95和0.98。
与相反顺序相比，AC之前给予DOC可减少DOC的剂量降低并具有更高的RDI。开展更大规模的试验评估蒽环类药物之前给予DOC的顺序是合理的。
